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ABSTRACT BOOK
22ND ANNUAL MEETING
Gaylord National on the Potomac
WASHINGTON, DC
SEPTEMBER 21-24, 2011
Also includes:
• Disclosures for all presenters
• Speakers’ learning objectives and recommended reading
What happens in DC
doesn’t have to stay in DC
The webcast of the 2011 NAMS Annual Meeting
lets you take advantage of the meeting’s educational
riches year-round, at your convenience.
If you miss part of the meeting or just want to revisit some sessions, this free
on-demand webcast is your answer.
Photos used with permission from Microsoft
The webcast will capture all plenary sessions as well as the Pre-Meeting
Symposium and let you select individual presentations for targeted viewing.
It will be freely available to all through September 15, 2012. It’s a great way to
reinforce your learning at your leisure and according to your schedule.
The free webcast will be posted soon after the meeting
on the NAMS website at:
www.menopause.org/meetings/webcast.aspx
Stay tuned for webcast launch announcements from NAMS
via email blast and Facebook and Twitter postings.
270
Contents
Key to Abstracts . . . . . . . . . . . . . . . . . . . . . . . . 4
Invited Speakers’ Abstracts & Learning Objectives . . . . . . . . 7
Scientific Session Speakers’ Abstracts . . . . . . . . . . . . .
32
Basic Science Poster Presentations . . . . . . . . . . . . . . . 40
Clinical Poster Presentations . . . . . . . . . . . . . . . . . . 44
Disclosure Statement. . . . . . . . . . . . . . . . . . . . .
67
Key to Disclosures . . . . . . . . . . . . . . . . . . . . . .
68
Disclosures . . . . . . . . . . . . . . . . . . . . . . . . . . 69
Invited Speakers’ Recommended Reading . . . . . . . . . . . 73
Call for Abstracts 2012 Annual Meeting . . . . . Inside Back Cover
3
Key to Abstracts
Invited Speakers’ Abstracts
Speakers
Scientific Session Speakers’ Abstracts
Page #
Speakers
Page #
David F. Archer, MD, NCMP . . . . . . . . . . . . . . . . . 19
Susan E. Appt, DVM . . . . . . . . . . . . . . . . . . . . 38
Raquel D. Arias, MD . . . . . . . . . . . . . . . . . . . . 15
David F. Archer, MD, NCMP . . . . . . . . . . . . . . . . 38
Gloria A. Bachmann, MD . . . . . . . . . . . . . . . . . . 39
Lauren L. Drogos, MA. . . . . . . . . . . . . . . . . . . 39
Herbert Benson, MD . . . . . . . . . . . . . . . . . . . . 31
Kristine Ensrud, MD, MPH. . . . . . . . . . . . . . . . . 36
Janet S. Carpenter, PhD, MSN, FAAN . . . . . . . . . . . . 27
Hadine Joffe, MD, MSc . . . . . . . . . . . . . . . . . . 37
Susan R. Davis, MBBS, FRACP, PhD . . . . . . . . . . . . . 26
Matthew Jorgensen, PhD . . . . . . . . . . . . . . . . . 34
Kristine Ensrud, MD, MPH . . . . . . . . . . . . . . . . . 27
Murray A. Freedman, MS, MD . . . . . . . . . . . . . . . 14
Ellen W. Freeman, PhD . . . . . . . . . . . . . . . . . . . 27
Steven R. Goldstein, MD, FACOG, CCD, NCMP . . . . . . . .
Martha Gulati, MD, MS, FACC, FAHA . . . . . . . . . . . .
7
17
Steven T. Harris, MD, FACP . . . . . . . . . . . . . . . . . 23
Candace J. Heisler, JD . . . . . . . . . . . . . . . . . . . 29
Kristijan Kahler, PhD, RPh . . . . . . . . . . . . . . . . . 33
Sobia Khan, MD, NCMP . . . . . . . . . . . . . . . . . . 35
Antonio Lombardi, MD . . . . . . . . . . . . . . . . . . 34
Santiago Palacios, MD, PhD . . . . . . . . . . . . . . . . 34
Barbara Parry, MD . . . . . . . . . . . . . . . . . . . . 37
JoAnn V. Pinkerton, MD, NCMP . . . . . . . . . . . . . . 32
Hadine Joffe, MD, MSc . . . . . . . . . . . . . . . . . . . 12
JoAnn V. Pinkerton, MD, NCMP . . . . . . . . . . . . . . 36
Ann E. Kearns, MD, PhD . . . . . . . . . . . . . . . . . . 22
David J. Portman, MD . . . . . . . . . . . . . . . . . . . 33
Andrea Z. LaCroix, PhD . . . . . . . . . . . . . . . . . . . 27
Susan Reed, MD, MPH . . . . . . . . . . . . . . . . . . . 33
Gail A. Laughlin, PhD . . . . . . . . . . . . . . . . . . . 25
Peter F. Schnatz, DO, FACOG, FACP, NCMP . . . . . . . . . 35
Robert Lindsay, MBChB, PhD, FRCP . . . . . . . . . . . . . 24
James A. Simon, MD, CCD, NCMP, FACOG . . . . . . . . . 36
Emma A. Meagher, MD . . . . . . . . . . . . . . . . . . . 18
Claudio N. Soares, MD, PhD, FRCPC . . . . . . . . . . . . 39
Alec J. Megibow, MD, MPH, FACH . . . . . . . . . . . . . . 9
Mary A. Tagliaferri, MD, LAc . . . . . . . . . . . . . . . . 38
Mary Jane Minkin, MD, FACOG, NCMP . . . . . . . . . . . 21
Masakazu Terauchi, MD, PhD . . . . . . . . . . . . . . . 37
Monica Morrow, MD, FACS . . . . . . . . . . . . . . . . . . 8
Rebecca C. Thurston, PhD . . . . . . . . . . . . . . . . . 32
Lori J. Mosca, MD, MPH, PhD . . . . . . . . . . . . . . . . 16
Rebecca C. Thurston, PhD . . . . . . . . . . . . . . . . . 38
Thomas H. Murray, PhD . . . . . . . . . . . . . . . . . . 28
Michelle P. Warren, MD, NCMP . . . . . . . . . . . . . . . 32
Lila E. Nachtigall, MD, NCMP . . . . . . . . . . . . . . . . 39
Miriam T. Weber, PhD . . . . . . . . . . . . . . . . . . . 37
Teri B. Pearlstein, MD . . . . . . . . . . . . . . . . . . .
13
Susan D. Reed, MD, MPH . . . . . . . . . . . . . . . . . . 27
William E. Reichman, MD . . . . . . . . . . . . . . . . . . 20
James A. Simon, MD, CCD, NCMP, FACOG . . . . . . . . . . 19
Patricia M. Speck, DNSc, APN, FNP-BC, . . . . . . . . . . . 29
DF-IAFN, FAAFS, FAAN
Patricia J. Sulak, MD . . . . . . . . . . . . . . . . . . . . 30
Jonathan L. Tilly, PhD . . . . . . . . . . . . . . . . . . . 10
4
In addition to the abstracts accepted for presentation in a Scientific Session, the following abstracts were accepted for poster
presentation. These abstracts are eligible for the 2011 NAMS Poster Prizes. The poster numbers listed below correspond with the
numbers on the posters displayed at the meeting.
Basic Science Presentations
Clinical Presentations
Presenting Author
Presenting Author
Abstract # Poster # Page #
Abstract # Poster # Page #
Jan Bohuslav, PhD
1113741
P-1
40
Lucy Abraham
1174677
P-19
44
Hoon Choi, MD
1113942
P-2
40
Wafa R. Al Omari, MD, FRCOG
1173365
P-20
44
Steriani Elavsky, PhD
1116853
P-3
40
Jose Mendes Aldrighi, MD, PhD
1116801
P-21
45
William Fisher, MA
1115666
P-4
40
Jose Mendes Aldrighi, MD, PhD
1116836
P-22
45
William Fisher, MA
1115702
P-5
41
Jose Mendes Aldrighi, MD, PhD
1116814
P-23
45
Tak Kim, MD, PhD
1174347
P-6
41
David F. Archer, MD, NCMP
1114448
P-24
45
Seung-Yup Ku, MD, PhD, NCMP
1116783
P-7
41
David F. Archer, MD, NCMP
1115729
P-25
46
Felicia Ojo, MPH
1090224
P-8
41
Gloria A. Bachmann, MD
1116365
P-26
46
Sophie Pettit
1174581
P-9
41
Jessica P. Brown, PhD
1116525
P-27
46
Peter F. Schnatz, DO, FACOG, FACP, NCMP
1115113
P-10
42
Carol A. Caico, PhD, OGNP, NCMP 1069444
P-28
47
Mindy S. Christianson, MD
1107766
P-29
47
Peter F. Schnatz, DO, FACOG, FACP, NCMP
1115034
P-11
42
Craig Crandall, PhD
1170986
P-30
47
Sonali Shah, MBA, MS, RPh
1108042
P-12
42
Lori A. Cray, PhD
1116468
P-31
47
Jose M. Soares, Jr., MD, PhD
1116545
P-13
43
Sue E. Dasen, MS
1115259
P-32
48
Regina Teixeira Gomes, PhD
1114259
P-14
43
Lino Del Pup, MD
1093993
P-33
48
Regina Teixeira Gomes, PhD
1114827
P-15
43
Catherine E. Doyle, RN, BScN, CON(C), NCMP
1112361
P-34
48
Regina Teixeira Gomes, PhD
1114818
P-16
44
Cindy M. Duke, BS, MS, MD, PhD 1169466
P-35
48
Carina Verna, MD
1114834
P-17
44
Robert R. Freedman, PhD
1113686
P-36
49
Carina Verna, MD
1114991
P-18
44
Margery L.S. Gass, MD, NCMP
1114850
P-37
49
Linda M. Gerber, PhD
1114740
P-38
49
Carolyn Gibson, MPH, MS
1174016
P-39
50
Miguel Gonzales-Izquierdo, MD
1171889
P-40
50
Miguel Gonzales-Izquierdo, MD
1171910
P-41
50
Vaidyanathan Gowri, MD
1165079
P-42
50
Rhoda Jamadar
1162971
P-43
51
Xuezhi Jiang, MD
1115042
P-44
51
Roksana Karim, MBBS, PhD
1116777
P-45
51
JangHeub Kim, MD
1173593
P-46
52
5
Key to Abstracts (continued)
Clinical Presentations
Presenting Author
Clinical Presentations
Abstract # Poster # Page #
Michael Krychman, MD
1111965
P-47
52
Seung-Yup Ku, MD, PhD, NCMP
1112933
P-48
52
Ji Young Lee
1113943
P-49
52
Sonia Maria Rolim Lima, MD, PhD 1122444
P-50
53
Sonia Maria Rolim Lima, MD, PhD 1122461
P-51
53
Sara E. Looby, PhD, ANP
1173773
P-52
53
Ricardo V. Maamari, MD, NCMP
1114478
P-53
53
Wendy L. Marsh, MD, MS
1165714
P-54
54
Kelsey E. Mills, HBSc, MD
1116753
P-55
54
Alvaro Monterrosa-Castro
1114136
P-56
54
Alvaro Monterrosa-Castro
1114143
P-57
54
Laura Moral
1114222
P-58
55
Lila E. Nachtigall, MD, NCMP
1170180
P-59
55
Eliana Aguiar Petri Nahas, MD
1113743
P-60
55
Belal Naser, MD
1114933
P-61
56
Katherine M. Newton, PhD, RN
1116563
P-62
56
Katherine M. Newton, PhD, RN
1116793
P-63
Alice I. Nichols, PhD
1115235
Betania Ogando
Presenting Author
Abstract # Poster # Page #
Rekha M. Sathyanarayana, MT (ASCP)
1114106
P-76
60
Lynnette Leidy Sievert, PhD
1116856
P-77
60
Tasneem Siyam, BSc, Pharm
1115490
P-78
60
Michael C. Snabes, MD, PhD
1174650
P-79
61
Claudio N. Soares, MD, PhD, FRCPC
1115616
P-80
61
Claudio N. Soares, MD, PhD, FRCPC
1175107
P-81
61
Claudi N. Soares, MD, PhD, FRCPC
1116464
P-82
61
Lily Stojanovska, BSc, MSc, PhD
1116639
P-83
62
Lily Stojanovska, BSc, MSc, PhD
1116643
P-84
62
Cynthia A. Stuenkel, MD, NCMP
1115171
P-85
62
Sandra Teixeira
de Araujo Moraes, MD, PhD
1079511
P-86
62
Sandra Teixeira
de Araujo Moraes, MD, PhD
1087056
P-87
63
56
Sandra Teixeira
de Araujo Moraes, MD, PhD
1087048
P-88
63
P-64
56
Kristi A. Tough, MD, NCMP
1163153
P-89
63
1116781
P-65
57
Shigeto Uchiyama
1116613
P-90
64
Marcia A. Padua, MD
1115051
P-66
57
Tomomi Ueno
1116615
P-91
64
JoAnn V. Pinkerton, MD, NCMP
1115721
P-67
57
Maria S. Velasco, MD
1112387
P-92
64
David J. Portman, MD
1114310
P-68
57
Maria S. Velasco, MD
1116767
P-93
65
Beth A. Prairie, MD, MPH
1157930
P-69
58
Michelle P. Warren, MD, NCMP
1116010
P-94
65
Beth A. Prairie, MD, MPH
1169825
P-70
58
Catherine J. Wheeler, MD
1164772
P-95
65
Josiane Rocha
1116704
P-71
58
Catherine J. Wheeler, MD
1172778
P-96
65
Josiane Rocha
1116776
P-72
59
Jennifer Whiteley, EdD, MSc, MA 1114622
P-97
66
Josiane Rocha
1116732
P-73
59
Mariano Zacarias-Flores, MD
1116743
P-98
66
Patricia A. Rouen, PhD, FNP
1115258
P-74
59
P-99
66
1114916
P-75
59
Jacqueline Zummo, MS, MPH, MBA
1115017
Jae Hong Sang, MD
6
but not with such precision. This lecture will deal with my observations of this
issue in gynecology using transvaginal ultrasound (TV U/S), although the
problems associated with increased sensitivity of imaging exist in many other
clinical fields as well. My thesis is that as we see more and more detail the
response to what we see has often been based on old and thus preconceived
notions, and not on newer well-organized and well-designed studies to
determine the prevalence of particular findings and their clinical significance.
Information obtained with increasingly refined technology cannot simply be
handled according to old established principles. Newer studies must be made
before clinical recommendations can be made. We must be careful not to over
interpret such findings that may be much more common and less ominous
that previously
Plenary Symposium
#1believed. The vaginal probe has revolutionized gynecology.
Higher frequency probes in close proximity to the structure being studied
have created a degree of image magnification that is as if we are doing
Presidential Symposium—“Incidental Findings
on Imaging:
Friend (sonomicroscopy).
or Foe?” We are seeing
ultrasound through
a low power microscope
things with ultrasound that you cannot see with the naked eye. Furthermore,
the ease of performing TV U/S, and its increasingly routine use for
surveillance, has resulted, in my opinion, in an explosion of incidental
findings that are much more common and more innocuous than previously
realized. There are many examples in gynecology but I will concentrate on
two that are very common and relevant to menopausal patients. These are 1)
Simple ovarian cystic structures and 2) Incidental endometrial “thickening”
The Increased Sensitivity of Transvaginal Ultrasound: Do We See Too
in non bleeding postmenopausal women. Forty years ago the dictum that a
Much?
palpable postmenopausal ovary was abnormal was put forth by Dr. Hugh
Steven R. Goldstein, MD, FACOG, CCD, NCMP. Obstetrics & Gynecology,
Barber. When ultrasound (then transabdominal ultrasound) began to see
New York University School of Medicine, New York, NY
postmenopausal cystic structures these were promptly removed as potentially
malignant. 25 years ago the first small observational study began to suggest
The ascertainment of diagnostic medical information through most of the
that unilocular unilateral cysts were invariably benign and could be managed
20th Century relied on techniques like inspection, palpation, and auscultation
expectantly. Abundant data from prospective screening studies have
as noninvasive ways to obtain information about internal anatomy, both
confirmed that observation. They have also shown the incidence of unilocular
normal and abnormal, as well as physiology which when not normal we call
cystic adnexal structures in postmenopausal women can be as high as 18%.
“pathology”. Sensitivity of imaging modalities has become so refined that we
The field has “matured” to where almost all clinicians will now counsel such
are seeing structures either never before appreciated or sometimes appreciated
patients for conservative management. Twenty years ago the first reports of
but not with such precision. This lecture will deal with my observations of this
a thin distinct endometrial echo in postmenopausal patients with bleeding
issue in gynecology using transvaginal ultrasound (TV U/S), although the
surfaced. Abundant prospective data from multicentered trials showed that
problems associated with increased sensitivity of imaging exist in many other
the incidence of malignancy in postmenopausal patients with bleeding when
clinical fields as well. My thesis is that as we see more and more detail the
the endometrial echo measures < 4mm on transvaginal ultrasound is 1/917.
response to what we see has often been based on old and thus preconceived
In 2009 ACOG stated “when transvaginal ultrasound is performed for patients
notions, and not on newer well-organized and well-designed studies to
with postmenopausal bleeding and an endometrial thickness <4mm is found
determine the prevalence of particular findings and their clinical significance.
endometrial sampling is not required”. Unfortunately most clinicians who
Information obtained with increasingly refined technology cannot simply be
understood that a thin distinct endometrial echo in such patients excludes
handled according to old established principles. Newer studies must be made
malignancy, have still inappropriately assumed that a thick echo in nonbefore clinical recommendations can be made. We must be careful not to over
bleeding patients is abnormal and requires intervention. The prevalence of
interpret such findings that may be much more common and less ominous
non thin endometrial echo on TV U/S in asymptomatic postmenopausal
that previously believed. The vaginal probe has revolutionized gynecology.
women is 10-17%. Furthermore13% of asymptomatic postmenopausal
Higher frequency probes in close proximity to the structure being studied
women will have an endometrial polyp on TV U/S. The risk of malignancy
have created a degree of image magnification that is as if we are doing
is such imaged structures, absent bleeding, is less than 1 in 250 yet the
ultrasound through a low power microscope (sonomicroscopy). We are seeing
complication rate from operative hysteroscopy in this elderly group is as high
things with ultrasound that you cannot see with the naked eye. Furthermore,
as 3.6%. The increasing sensitivity of the vaginal probe can and should be a
the ease of performing TV U/S, and its increasingly routine use for
wonderful tool for the gynecologist. However studies on the prevalence and
surveillance, has resulted, in my opinion, in an explosion of incidental
significance of the things one can see on such imaging must be carried out if
findings that are much more common and more innocuous than previously
it is to be incorporated appropriately. Remember the credo –“above all else do
realized. There are many examples in gynecology but I will concentrate on
no harm!
two that are very common and relevant to menopausal patients. These are 1)
Simple ovarian cystic structures and 2) Incidental endometrial “thickening”
in non bleeding postmenopausal women. Forty years ago the dictum that a
palpable postmenopausal ovary was abnormal was put forth by Dr. Hugh
Barber. When ultrasound (then transabdominal ultrasound) began to see
postmenopausal cystic structures these were promptly removed as potentially
malignant. 25 years ago the first small observational study began to suggest
that unilocular unilateral cysts were invariably benign and could be managed
expectantly. Abundant data from prospective screening studies have
confirmed that observation. They have also shown the incidence of unilocular
cystic adnexal structures in postmenopausal women can be as high as 18%.
The field has “matured” to where almost all clinicians will now counsel such
patients for conservative management. Twenty years ago the first reports of
a thin distinct endometrial echo in postmenopausal patients with bleeding
surfaced. Abundant prospective data from multicentered trials showed that
the incidence of malignancy in postmenopausal patients with bleeding when
the endometrial echo measures < 4mm on transvaginal ultrasound is 1/917.
In 2009 ACOG stated “when transvaginal ultrasound is performed for patients
with postmenopausal bleeding and an endometrial thickness <4mm is found
endometrial sampling is not required”. Unfortunately most clinicians who
understood
that a thin distinct endometrial echo in such patients excludes
Learning
Objectives:
malignancy, have still inappropriately assumed that a thick echo in nonpatientsof
is this
abnormal
and requires participants
intervention. The
prevalence
of to:
At thebleeding
conclusion
presentation,
should
be able
non thin endometrial echo on TV U/S in asymptomatic postmenopausal
is 10-17%.
of asymptomatic
postmenopausal
• women
Describe
how theFurthermore13%
use of endometrial
ultrasonography
can reduce surgical interventions
women will have an endometrial polyp on TV U/S. The risk of malignancy
• is
State
prevalence
recognize
the
ovarian cysts
such the
imaged
structures,and
absent
bleeding, is
lesssignificance
than 1 in 250of
yetpostmenopausal
the
complication
rate
from
operative
hysteroscopy
in
this
elderly
group
is
as
high
• State the prevalence and explain the significance of “thickened” endometrial echo on transvaginal
as 3.6%. The increasing sensitivity of the vaginal probe can and should be a
ultrasound
patients
wonderful
tool in
fornonbleeding
the gynecologist.postmenopausal
However studies on the
prevalence and
significance of the things one can see on such imaging must be carried out if
it is to be incorporated appropriately. Remember the credo –“above all else do
no harm!
Speakers’ Abstracts & Learning Objectives
7
Speakers’ Abstracts & Learning Objectives (continued)
Plenary Symposium #1
Presidential Symposium—“Incidental Findings on Imaging: Friend or Foe?”
MRI for Breast Cancer Screening & Staging
Monica Morrow, MD, FACS. Memorial Sloan Kettering Cancer Center, New
York, NY
MRI is able to visualize small tumor deposits not evident on mammography
or clinical exam that previously could only be identified on pathologic exam.
While this presents new opportunities, it also results in problems when MRI
findings result in more aggressive surgical treatment in clinical situations in
which outcomes are well documented to be good without the use of MRI. In
the screening setting, MRI has been shown to have a higher sensitivity for
invasive cancer detection than mammography in known or suspected BRCA
mutation carriers leading to fewer node positive cancers and detection of
smaller cancers in the MRI screened group. In a meta-analysis comparing
high risk screening with MRI and mammography, the sensitivity of
mammography was 32% (95% CI 23-41) and that of MRI was 75% (95% CI
62-88). Whether these results are specific to the unique biology of breast
cancers in BRCA mutation carriers or can be extrapolated to women at
increased risk from other causes is uncertain. In women with breast cancer,
additional disease is detected by MRI in 16% of cases (95% CI 6-34%).
However, two prospective randomized trials (COMICE, MONET) have not
shown an improvement in the ability to successfully select patients for breast
conservation or to obtain negative margins with the use of MRI. To date,
retrospective studies do not show a decrease in local recurrence after breast
conservation with MRI use. Downsides of MRI include cost, false positives
leading to a delay in cancer treatment during work-up, and an association
between pre-op MRI and the increased use of ipsilateral mastectomy and
contralateral prophylactic mastectomy. Odds ratios for mastectomy with MRI
range from 1.5-3 after adjustment for other variables MRI is useful in problem
areas of management such as occult primary cancer presenting as axillary
adenopathy, in the BRCA carrier who chooses breast conservation, and in
patients receiving neoadjuvant chemotherapy. It may be helpful in clinical
problem solving in selected cases, but in the absence of evidence of patient
benefit should not be considered a routine part of the pre-operative work-up
or follow-up of the breast cancer patient.
Learning Objectives:
At the conclusion of this presentation, participants should be able to:
• Identify and describe groups of women for whom MRI screening has been shown to be beneficial
• R
ecognize the lack of a difference in short- or long-term surgical outcomes for breast cancer
patients staged with and without MRI
8
Plenary Symposium #1
Presidential Symposium—“Incidental Findings on Imaging: Friend or Foe?”
Incidental Imaging Findings: Strategies to Minimize Their Impact
Alec J. Megibow, MD, MPH, FACH. New York University - Langone Medical
Center, New York, NY
For better or worse, some form of imaging has become expected as part of the
evaluation of patients for virtually all clinical problems. Current imaging
technology provides referring clinicians with a rapid, safe and accurate
assessment of patients and has become focal points for decision making.
However, as more and more patients undergo imaging tests there is increasing
frequency of detection of findings that were likely not sought after, so-called
incidental findings. There are occasions where unsuspected findings actually
benefit patients, e.g. detection of an unsuspected aortic aneurysm, urinary
calculi, and silent hydronephrosis. Yet despite the overwhelming pre-test
probability that the findings are of no consequence to the patient, their
detection often results in extra (and usually unnecessary) further testing,
patient anxiety, referring clinician frustration, cost, radiation, and even-in
some cases- surgical sampling. The root cause of the problems associated
with these findings is variable security by both radiologists and clinicians to
deal with uncertainty, often excused as fear of medico-legal consequences.
Radiologists have recognized the significance of these findings and have
sought to create some form of guidance to aid the individual confronted with
an incidental finding. The approach has been the creation of decision trees
that stratify the likelihood that an individual finding is benign, malignant or
indeterminate. The decision trees were created in a formal process with teams
of imaging experts reviewing the literature and then sharing with the entire
group for comment and further refinement. The project required four years to
complete; these decision trees have been published in October of 2010. While
those of us involved in their creation are convinced that they will be modified
over time, we believe that they represent a credible “first pass” from which
refinements can be added. This talk will review a radiologist’s perspective of
the problem of incidental findings, economic implications of their detection,
and review the application of the imaging decision trees in abdominal
diseases.
Learning Objectives:
At the conclusion of this presentation, participants should be able to:
• Characterize the problem of incidental findings in the abdomen
• Describe the process by which decision trees have been adopted in the literature
• Explain how these decision trees can increase the confidence level of interpreting radiologists
9
Speakers’ Abstracts & Learning Objectives (continued)
Keynote Address
Ovarian Aging: Can Science Turn Back the Clock?
Jonathan L. Tilly, Ph.D. Vincent Center for Reproductive Biology,
Massachusetts General Hospital/ Harvard Medical School, Boston, MA.
Ovarian aging is defined by a declining ovarian reserve, decreased ovulation
and reduced egg quality. Oocytes are prone to aging-associated aneuploidy
and meiotic spindle abnormalities, leading to increased infertility, fetal loss
and birth defects – most notably Down syndrome. Despite extensive research,
no interventions have been identified that mitigate the deleterious effects of
aging on the ovaries. Mice also exhibit an age-related decline in their ovarian
reserve, as well as an aging-associated increase in oocyte aneuploidy and
spindle defects. We have therefore used mice to explore approaches for
improving ovarian function in aging females, and then used this information
for initial validation in studies of human ovaries. For example, we have been
exploring the use of female germline or oogonial stem cells (OSCs) as both
agents and targets for increasing the ovarian reserve. Although our initial
studies identifying the existence of OSCs in adult mouse ovaries (Nature 2004
428:145-50) were controversial, OSCs have recently been isolated from
postnatal mouse ovaries by several labs and shown by intraovarian
transplantation to generate eggs that yield viable offspring (Nature Cell Biol
2009 11:631-6). Further, aged mouse ovaries devoid of oocytes retain a small
pool of premeiotic germ cells that remain capable of producing oocytes when
transferred to a young adult ovarian environment (Aging 2009 1:971-8).
Accordingly, failure of these cells to support the ovarian reserve with age may
reflect both germ cell-intrinsic changes as well as deterioration of somatic
microenvironments that support OSC function. Other studies have focused
on identification of agents that enhance oogenesis in adult ovaries, an
objective that will be facilitated by our recent validation of an in-vitro
screening assay that predicts the ability of a given compound to stimulate
oocyte formation when administered to adult female mice in vivo (Cell Cycle
2010 9:339-49). Our current efforts are now directed at characterizing
a comparable population of oocyte-producing stem cells in ovaries of
reproductive age women, and discerning how the aging process affects them.
Another approach we have taken is dietary caloric restriction (CR), which
extends lifespan and attenuates the severity of many aging-related health
complications in diverse species. Institution of CR in adult female mice results
in a remarkable near-doubling of natural reproductive lifespan with vast
improvements in offspring survival (Aging Cell 2008 7:622-9). Follow-up
studies have revealed that CR prevents the aging-related decline in total and
metaphase-II oocyte yield, and completely abolishes aging-related
increases in oocyte aneuploidy, chromosome misalignment, meiotic spindle
abnormalities and mitochondrial dysfunction, all of which occur in oocytes
of aging ad libitum-fed control animals (Proc Natl Acad Sci USA 2011 in
press). This opens the prospects for development of CR mimetic-based
approaches to safely circumvent the negative impact of aging on germline
chromosomal stability and its segregation in eggs. Finally, it is worthwhile
mentioning that ovarian failure marks a time in life defined by infertility
and a cessation of cyclic hormone secretion from the gonads. Although the
ramifications of the loss of fertile potential are clear, the consequences of
impaired ovarian endocrine function are much more diffuse because of the
large number of tissues in the body affected by ovarian-derived hormones
such as estrogen. This latter point is exemplified by the diverse spectrum of
health issues that become manifest in women after menopause. Strategies that
prevent or delay ovarian failure therefore hold clinical potential not just for
fertility reasons but also for improving the overall quality of life in women as
they age. Although this latter goal may be viewed as unreachable by some,
past work with mice has shown that sustaining ovarian function through
maintenance of an adequate ovarian reserve with age does in fact yield
immense health benefits without an increase in cancer, especially in steroidresponsive tissues (Proc Natl Acad Sci USA 2007 104:5229-34). Thus, the
concept of an “ovarian replacement therapy” is, in our opinion, at least worth
additional testing. Supported by NIA MERIT Award R37-AG012279.
Learning Objectives:
At the conclusion of this presentation, participants should be able to:
• Explain how increasing chronological age negatively affects ovarian function
• D
escribe approaches currently being developed in mice that can be used to attenuate or
prevent aging-associated deterioration of ovarian function
• Discuss how work on ovarian aging in mice supports the notion that functional lifespan of human
ovaries may be amenable to therapeutic manipulation
10
Plenary Symposium #2
“Staging Reproductive Aging: An Update from STRAW+10”
Supported by an unrestricted educational grant from Eli Lilly and Company
Staging Reproductive Aging: An Update from STRAW+10
John F. Randolph, Jr., MD1, Frank J. Broekmans, PhD2, Siobán D.
Harlow, PhD1. 1University of Michigan, Ann Arbor, MI; 2Department
of Reproductive Biology, University Medical Center Utrecht, Utrecht,
Netherlands
This plenary symposium will review the work of a 2-day symposium,
“STRAW+10: Addressing the Unfinished Agenda of Staging Reproductive
Aging,” convened immediately before the 2011 NAMS Annual Meeting as
a collaborative effort among the National Institute on Aging, the Office of
Research on Women’s Health, The North American Menopause Society, the
American Society for Reproductive Medicine, the International Menopause
Society, and The Endocrine Society. The STRAW+10 effort aims to build
on the 2001 STRAW (STtaging Reproductive Aging in Women) workshop,
which produced a consensus document whose recommendations have been
the standard for classifying female reproductive aging through menopause
and have significantly framed research in the field over the past decade. In
the 10 years since STRAW, our understanding of the ovary–brain interactions
that occur before and after the final menstrual period has advanced considerably,
as has our understanding of the implications for women’s health. These
advances are the impetus for STRAW+10, whose primary objectives are
to: (1) discuss criteria for the onset of early menopause in light of new
population-based data relating to reproductive hormones and ovarian markers;
(2) assess how to apply reproductive staging algorithms to women with higher
body mass index and women who smoke; (3) provide recommendations
for staging of women following gynecological surgery, chemotherapy,
and hormone therapy as well as women with polycystic ovarian syndrome
and chronic diseases like HIV/AIDS; and (4) assess potential criteria for
staging postmenopause. The individual presentations in this plenary symposium
will summarize the STRAW+10 symposium in several ways. The first will
review recent advances in our understanding of FSH stages of the
menopause transition, including improved modeling of the decline in
ovarian reserve and the impact of body mass index. The second will
discuss antimullerian hormone and antral follicle count as improved markers of
fertility decline and onset of the menopause transition. The final presentation
will outline preliminary recommendations from STRAW+10, which will be
published in full form in the coming months.
11
Speakers’ Abstracts & Learning Objectives (continued)
Plenary Symposium #3
“Identifying & Treating Depression in Midlife Women”
Supported in part by grant funding from Pfizer Inc.
Menopause, Depression & Hormones: What’s the Connection?
Hadine Joffe, MD, MSc. Department of Psychiatry, Division of Sleep
Medicine, Massachusetts General Hospital, Boston, MA
The perimenopause is a period of risk for first-onset of and recurrence of
depression in midlife women. While the majority of women who suffer from
depression in midlife have previously experienced depression as young adults,
some women experience their first episode of depression during the
perimenopause. The basis for the increased risk of depression during this
period of reproductive life is multi-factorial and varies among women.
Common risk factors include a previous history of depression, stressful life
events, and the perimenopause itself. Perimenopause may contribute to the
increased risk of depression through several pathways, including fluctuating
levels of estradiol and other reproductive hormones, and sleep disturbance
secondary to hot flashes. Hot flashes and sleep disturbance are strongly
associated with depression in perimenopausal women, and women with
menopause-associated depression commonly experience hot flashes and sleep
disturbance concurrent with their depression. The frequent comingling of
these symptoms suggests that they may share a common etiologic pathway in
some women. Understanding the potential contribution of perimenopausal
hormone changes, menopausal symptoms, stressful life events, and recurrence
of depression, to the etiology of depression in midlife women will inform our
ability to treat depression in this population. Treatment strategies for
individual women will vary with the key risk factors identified for that woman
and the relative prominence of specific co-occurring symptoms, such as sleep
disturbance. Understanding the pathways that link these frequently
commingled symptoms together will enable clinicians to optimize treatment
for individual women who experience depression during the perimenopause.
Learning Objectives:
At the conclusion of this presentation, participants should be able to:
• Recognize the role of perimenopause and menopausal symptoms in the risk of depression in midlife women
• Describe the association of depression with fluctuating estradiol levels, hot flashes, and sleep disturbance
12
Plenary Symposium #3
“Identifying & Treating Depression in Midlife Women”
Supported in part by grant funding from Pfizer Inc.
Depression in Midlife Women: Identification & Treatment
Teri Pearlstein, MD. Psychiatry & Human Behavior, Alpert Medical School
at Brown University, Providence, RI
Depressive and anxiety symptoms may first appear or increase in midlife
women. Although for many perimenopausal women these symptoms are
“subsyndromal”, it is important that midlife women be screened for mood
and anxiety disorders that negatively impact daily life and functioning.
Screening scales can be utilized for both diagnostic assessment and for
monitoring response to treatment. Treatment for depression includes both
pharmacological and non-pharmacological therapies, such as psychotherapy.
Studies have been conducted with antidepressant medications in both
perimenopausal and postmenopausal women. The use of antidepressant
medications in midlife women should take into account specific symptoms,
potential side effects, and concurrent medications. Studies have reported
mixed results about a possible differential response to selective serotonin
reuptake inhibitors before and after the menopausal transition. Estrogen may
have a unique role in the improvement of mood in depressed perimenopausal
women, both as a single treatment and as an adjunctive treatment.
Augmentation strategies may be considered if depressive symptoms do not
respond to antidepressant medication or estrogen. Complementary and
alternative treatments may have a role in the treatment of depression in midlife
women who do not desire, or do not tolerate, psychotropic medication or
hormones.
Learning Objectives:
At the conclusion of this presentation, participants should be able to:
• Effectively evaluate midlife women for depressive symptoms
• Identify pharmacologic and nonpharmacologic treatments for depression, and choose among them
to address the needs and concerns of individual midlife women
13
Speakers’ Abstracts & Learning Objectives (continued)
Plenary Symposium #4
“When Sex Hurts”
Supported in part by grant funding from Novo Nordisk Inc., Pfizer Inc., and Warner Chilcott
Prevalence, Etiology & Diagnosis of Vulvovaginal Atrophy
Murray A. Freedman, MS, MD. Department of Obstetrics & Gynecology,
Medical College of Georgia, Augusta, GA
The classification of painful sex disorder in the DSM IV includes a number
of etiologic factors, but because of time constraints (for this NAMS
presentation), this discussion of “painful sex” will be limited to dyspareunia
as it relates to vulvovaginal atrophy (VVA) and estrogen insufficiency in periand postmenopausal women. While the primary focus will address “painful
sex”, it should be emphasized that the discussion applies equally to the
enhancement of pleasurable sex, not just the prevention of VVA and
dyspareunia. While there are 3 inevitable, inexorable factors that adversely
effect female sexuality—-age, hormones and relationship issues—-aging and
partnership issues will be addressed in only a cursory manner. The prevalence
of VVA has been vastly underestimated because most studies and surveys in
the literature have typically reported symptoms of sexual complaints and/or
dysfunction rather than having been based upon physical examination. There
is a paucity of scientific data based on the actual physical findings of atrophy
in hypoestrogenic postmenopausal women. 1500 postmenopausal women in
a clinical practice were examined for signs of VVA, including measurement
of vaginal pH. Data will be presented to suggest that a) the prevalence of VVA
in truly hypoestrogenic women (serum estradiol < 20 pg/ mL) is
approximately 85 %, and b) up to 15 % of postmenopausal women utilizing
‘adequate’ doses of estrogen supplementation exhibit signs of VVA. Vaginal
pH has been found to be a rapid, simple, accurate, inexpensive and
reproducible harbinger of VVA, and pH values > 5.0 are almost invariably
associated with physical evidence of VVA. Because of its embryologic
derivation (endoderm), the introitius is subject to the earliest morphologic
changes of VVA, and there are distinctive involutional changes at the vestibule
that characterize the atrophic process. While vaginal dryness, erythema and
loss of rugation are indicative of VVA, the early anatomic alterations at the
intoitus (particularly the contraction and loss of elasticity) are actually more
pathognomonic of the atrophic process. It is the introital involution rather
than vaginal atrophy per se that is initially responsible for dyspareunia in
hypoestrogenic women. While lubricants may assuage dryness and discomfort
temporarily, the atrophic process often continues unabated. The combination
of diminished or absent sexual activity and estrogen insufficiency compounds
the atrophic process, and in a hypoestrogenic environment, VVA becomes an
inevitable consequence.
Learning Objectives:
At the conclusion of this presentation, participants should be able to:
•
•
•
•
14
Describe the incidence and prevalence of vaginal atrophy and its impact on sexual health
Identify and distinguish causes of dyspareunia in peri- and postmenopausal patients
Recognize the various physical changes associated with vaginal atrophy
Implement strategies to ensure that they routinely ask peri- and postmenopausal patients about
their vaginal and sexual health
Plenary Symposium #4
“When Sex Hurts”
Supported in part by grant funding from Novo Nordisk Inc., Pfizer Inc., and Warner Chilcott
Treatment Options for Vaginal Atrophy & Dyspareunia
Raquel D. Arias, MD. Obstetrics & Gynecology, Keck School of Medicine,
University of Southern California, Los Angeles, CA
The human vagina is more than a potential space. It is a dynamic, complex
micro-ecosystem whose integrity supports symptom-free elimination and
urination in addition to sexual function. Maintenance of vaginal health is
dependent on gross structural, microanatomic, immunologic, neural and
vascular integrity. It is therefore not surprising that intervention targeting a
single aspect of vaginal health maintenance yields only modest success. While
direct comparisons of hormonal, mechanical and topical (nonhormonal )
treatments are limited, a working knowledge of each will contribute to the
clinician’s ability to advise and guide care in the burgeoning demographic at
risk for dysfunction.
Learning Objectives:
At the conclusion of this presentation, participants should be able to:
• .Identify and manage vaginal moisture deficiency with local interventions that are either hormonal or nonhormonal
• Counsel peri- and postmenopausal patients on the benefits and risks associated with vaginal estrogen use
• Initiate individualized treatment plans for vaginal atrophy and dyspareunia in peri- and postmenopausal patients
15
Speakers’ Abstracts & Learning Objectives (continued)
Plenary Symposium #5
“Cardiovascular Disease in Postmenopausal Women:
Getting to the Heart of the Matter”
Supported in part by grant funding from Astellas
State of the Heart 2011—New Guidelines for Prevention
Lori J. Mosca, MD, MPH, PhD. Department of Medicine, Columbia
University, New York, NY
Learning Objectives:
Despite enormous progress in the awareness, prevention, and treatment of
cardiovascular disease (CVD) over the past decade, it remains the leading
cause of death among women and a major contributor to morbidity, decreased
quality of life, and health expenditures in the United States (1). One in three
adult females has CVD with a disproportionate prevalence of disease among
black females. Since 1984 the annual number of deaths due to CVD for
women has exceeded those for men. Nearly one half million women die of
CVD annually, accounting for nearly half of all their deaths. Nearly 3 million
women were discharged from short stay hospitals with CVD listed as the first
diagnosis in 2007. These statistics underscore the public health and economic
impact of CVD. According to a recent national survey, awareness of CVD as
the leading cause of death has nearly doubled among women (30% in 1997
to 54% in 2009) since national educational campaigns were initiated (2).
Despite the progress, awareness continues to lag among racial and ethnic
minorities compared to white women suggesting targeted educational
interventions need to be developed and evaluated to close the gap especially
because awareness of CVD risk has been linked to taking preventive action.
The majority of CVD in women is coronary heart disease (CHD) and
currently about 8 million women in the US are living with CHD (1). An
estimated half million women will have a new or recurrent myocardial
infarction (MI) or fatal CHD. Among women who have a recognized MI over
age 40 years 24% will die within 1 year compared to 18% of men. It is notable
that 2 out of 3 women who die suddenly of CHD had no previous symptom
which suggests that primary prevention must be a key strategy to reduce the
burden of CHD in women. Similar to trends in CVD, the death rate for CHD
is higher for black females than white females. Sex differences in the
presentation of CHD have been well established with women more likely to
present with angina compared to men while the initial presentation of CHD
in men is more likely to be MI or CHD death. A recent national survey
indicated that only about half of women knew the classic symptoms of heart
disease and significantly less knew the atypical symptoms which are more
common in women than men (2). Of concern was that only 53% of women
said they would call 9-1-1 if they thought they were having a heart attack but
79% said they would call if they thought someone else was. Substantial
evidence has documented the benefits of prevention to reduce the morbidity,
mortality, and costs associated with CVD in women. The American Heart
Association recently updated its guidelines for the prevention of CVD in
women (3). A notable change over previous guidelines is the shift from
evidence-based to effectiveness-based guidelines. The expert panel
emphasized that the efficacy of intervention observed in clinical trial settings
is often not realized in clinical practice. This gap may be related to the
diversity of women in practice settings and lack of adherence due to side
effects and other barriers. Other significant changes in the guidelines were
the addition of novel risk factors, such as pregnancy complication and
rheumatoid arthritis. The threshold for “high risk” was modified to >10% 10year absolute risk of CVD owing to the greater prevalence of stroke in some
and the data documenting traditional Framingham scores underestimate risk
in women. The 2011 guidelines also emphasized the need for more research
on how to better implement proven preventive strategies in women.
At the conclusion of this presentation, participants should be able to:
• .I ncorporate cardiovascular risk assessment, as established by American Heart Association (AHA) guidelines
on cardiovascular disease prevention in women, into patients’ annual examinations
• Advise women on how to implement new recommendations for the prevention of cardiovascular disease
16
Plenary Symposium #5
“Cardiovascular Disease in Postmenopausal Women:
Getting to the Heart of the Matter”
Supported in part by grant funding from Astellas
Coronary Disease & Stroke in Women: Strategies for Intervention
Martha Gulati, MD, MS, FACC, FAHA. Preventive Cardiology &
Women’s Cardiovascular Health, Ohio State University College of Medicine,
Columbus, OH
Coronary artery disease (CAD) remains the leading cause of death in both
men and women in the United States. Women differ from men in their clinical
presentation of coronary artery disease, their performance on diagnostic
tests, and their prevalence of coronary artery disease. The purpose of this
talk will be to discuss gender differences in presentation and treatment
of cardiovascular disease and stroke, with a focus on recent research and
guidelines for women and cardiovascular disease. The discussion will also
include cardiac syndrome X and recent research related to this syndrome.
Learning Objectives:
At the conclusion of this presentation, participants should be able to:
• D
escribe differences in coronary artery disease patterns in women as compared with men and the impact of
these differences on prognosis
• Identify women at risk for stroke, recognizing the increased prevalence of stroke in women compared with men
• Implement preventive strategies to reduce the risk of cardiovascular disease and stroke in women, and describe
the role of aspirin in primary and secondary prevention
17
Speakers’ Abstracts & Learning Objectives (continued)
Plenary Symposium #5
“Cardiovascular Disease in Postmenopausal Women:
Getting to the Heart of the Matter”
Supported in part by grant funding from Astellas
Clinical Challenges in Lipid Management
Emma A. Meagher, MD. University of Pennsylvania Health System,
Philadelphia, PA
Cardiovascular disease is the primary cause of death in American women,
accounting for more than 500,000 deaths per year. More women die from
cardiovascular disease (CVD) each year than from the next seven leading
causes of death combined. There is a need to better identify and treat women
who may be at risk for cardiovascular disease. Dyslipidemia is one of the
most important modifiable risk factors for coronary heart disease (CHD).
Low-density lipoprotein cholesterol (LDL-C) is the primary target of lipidmodifying therapy for the reduction of coronary risk in both genders.
However, there are important gender differences in the lipid profile that
warrant our attention. A significant body of evidence from numerous, wellcontrolled, randomized trials demonstrates that treatment with HMG-CoA
reductase inhibitors (statins) reduces morbidity and mortality from CVD.
Subgroup analyses of both primary and secondary prevention trials have
shown that lipid-modifying drugs offer benefits to women comparable to
those seen in men. While these observations are important and have resulted
in the adoption of standard of care approaches for the management of CVD
risk in men, they have not been uniformly adopted in the management of risk
in female patients. In addition, when reviewing these landmark statin trials it
is clear residual risk for CV events remains despite statin therapy. In women,
changes in high-density lipoprotein cholesterol (HDL-C) and triglyceride
levels are believed by many to be better predictors of coronary risk than LDLC or total cholesterol. Despite this, attempts to demonstrate that combination
therapy directed at HDL –C raising or triglyceride lowering have failed to
improve CVD outcome.
Learning Objectives:
At the conclusion of this presentation, participants should be able to:
• Implement appropriate pharmacotherapy to reduce LDL cholesterol and triglyceride levels in women
as indicated by the AHA guidelines
• Determine which women are appropriate candidates for pharmacotherapy to raise HDL cholesterol
levels according to the AHA guidelines
18
Plenary Symposium #6
“Debate—Is There Ever an Indication for Hormone Therapy in
an Asymptomatic Postmenopausal Woman?”
Is There Ever an Indication for Hormone Therapy in an Asymptomatic
Postmenopausal Woman?
James A. Simon, MD, CCD, NCMP, FACOG. George Washington
University School of Medicine, Washington, DC; and David F. Archer, MD,
NCMP, The Jones Institute for Reproductive Medicine, Eastern Virginia
Medical School, Norfolk, VA
In a special debate format, two experienced menopause practitioners will
present dueling arguments on whether hormone therapy is ever indicated in
an asymptomatic postmenopausal woman. Each debater will prepare both
affirmative and negative arguments, with supporting evidence, prior to the
debate, and their respective positions will be assigned randomly at the start of
the debate. The format will allow 15-minute presentations for each position
followed by 5-minute rebuttals on each side. An audience vote at the end will
determine the winner.
Learning Objectives:
At the conclusion of this presentation, participants should be able to:
• E xplain whether, when, and why hormone therapy might ever be an appropriate option for an
asymptomatic postmenopausal woman
19
Speakers’ Abstracts & Learning Objectives (continued)
NAMS/Pfizer Wulf H. Utian Endowed Lecture
History & Experience: The Direction of Alzheimer’s Disease
William E. Reichman, MD. Psychiatry, Faculty of Medicine, University of
Toronto, Toronto, ON, Canada
As the global population is projected to age substantially in coming decades,
the number of individuals who will develop Alzheimer’s disease (AD) is
expected to rise dramatically. The dementia syndrome arising from AD
includes progressive failure in memory and all other cognitive domains,
behavioural alterations, functional decline and ultimately, death. We have
come to understand that AD is likely to be multi-determined through
interactions between heritable causal and susceptibility genes, environmental
exposures, mid life health status and lifestyle choices. Additionally, mounting
scientific evidence suggests that the neuropathological processes
characteristic of AD can be detected several years prior to the onset of clinical
signs and symptoms. Thus, AD is now considered to have pre-symptomatic,
prodromal (mild cognitive impairment) and dementia phases. Through the
use of cerebrospinal biomarkers, volumetric neuroimaging, functional
neuroimaging, and cognitive stress tests, individuals at significant risk for
developing dementia due to AD can now be identified with greater sensitivity
and specificity. Not surprisingly, there is growing attention to successfully
identify interventions to halt or delay the clinical onset of AD. The biological
capacities of neurogenesis and neuroplasticity and the related concepts of
brain and cognitive reserve provide a rationale for developing techniques to
strengthen the cognitive abilities of older persons sufficiently to prevent
incident dementia. As the normal aging process is also strongly associated
with brain changes that lead to a weakening of some select cognitive domains
in healthy persons, there has been increasing interest in finding methods to
“keep our brains sharp” by maintaining or enhancing cognitive performance.
Not surprisingly, interest among the consumer public in learning how to
prevent cognitive loss and how to strengthen such abilities in mid and later life
appears to be steadily growing. This has led to the emergence of a new “Brain
Fitness” commercial industry in which structured, live cognitive training
programs, computerized games, internet based course work and other
“products” are being marketed and sold to consumers. However, the majority
of available brain fitness methods and products have scant scientific evidence
to support their effectiveness. Despite this caveat, ongoing research advances
do indeed support the potential for memory and other intellectual functions
to be strengthened and maintained through cognitive training, physical
exercise, dietary choices, social engagement and psychological stress
reduction.
Learning Objectives:
At the conclusion of this presentation, participants should be able to:
• Outline recent scientific advances for detecting Alzheimer’s disease prior to the onset of dementia
• S ummarize the most recent research findings on how to potentially maintain and strengthen cognitive function and
reduce the risk for developing dementia due to Alzheimer’s disease
• Describe the emerging “Brain Fitness” market and how best to advise patients and their families about preventing
Alzheimer’s disease
20
Plenary Symposium #7
“Addressing the Needs of Midlife Women Through & Beyond Breast Cancer”
Supported in part by grant funding from Pharmavite LLC
Quality of Life: Alternatives to Hormone Therapy for Vasomotor
Symptoms
Mary Jane Minkin, MD, FACOG, NCMP. Yale University School of
Medicine, New Haven, CT
80% of women experience vasomotor symptoms during the menopausal
transition. Women with breast cancer can be even more symptomatic; if they
are premenopausal at time of diagnosis, chemotherapy often renders them
suddenly hypoestrogenic.. If they are already postmenopausal and on
hormonal therapy, they will be required to stop. Virtually all women with
estrogen receptor positive tumors will be treated with either tamoxifen or
aromatase inhibitors, further exacerbating their vasomotor symptoms.
Although the most efficacious of the available therapies for managing
vasomotor symptoms, namely estrogen, is contraindicated in this population,
several categories of relief do remain available. Lifestyle changes that have
been shown to mitigate severity of vasomotor symptoms include smoking
cessation, exercise, and weight loss; adoption of healthier lifestyle measures
may even impact on the overall survival. Paced respiration and acupuncture
have been tried, with mixed results on efficacy, but not controversial on
safety.1Herbal and botanical approaches may be helpful. Controversies do
exist over both the efficacy and safety of both isoflavones and black cohosh
in this population. Non hormonal medications have been prescribed widely;
SSRI’s and SNRI’s are widely used in this group of patients. However, given
the special emotional vulnerability of the relatively young cancer survivors to
potential side effects of anti-depressants, such as decreased libido and weight
gain, these medications need to be prescribed judiciously. Special
consideration is merited in tamoxifen users, as certain SSRI’s such as
paroxetine can interact with tamoxifen’s metabolism, hence risking reduction
in chemo-efficacy of tamoxifen. Gabapentin has been used in breast cancer
survivors as well. Older therapies such as antihypertensives are rarely used
currently, given side effects and minimal efficacy. Given that sleep disruption
often accompanies vasomotor complaints, consideration needs to be given to
adjunctive use of sleep medications in this population. Vaginal atrophy is a
common accompaniment to vasomotor symptoms, and contributor to the
overall compromised quality of life particularly in the relatively young
experiencing abrupt menopause. Symptoms of vaginal discomfort thus must
be enquired in those experiencing vasomotor symptoms; while alternative
therapies such as polycarbophil moisturizers have shown promise in providing
symptomatic relief, judicial use of vaginal estrogen therapy may be a
consideration for some, given the minimal systemic absorption with the use
of low dose rings, tablets, and creams. Given the increased use of SERM’s and
projected possible use of aromatase inhibitors for breast cancer
chemoprevention, alternative therapies for vasomotor symptoms will become
even more relevant. Potential use of TSECs in this population may prove
beneficial in symptom prevention as well.
Learning Objectives:
At the conclusion of this presentation, participants should be able to:
• D
iscuss management of hot flashes with their breast cancer patients, ranging from lifestyle changes to
nonprescription therapies to prescription medications
• Counsel breast cancer patients on the potential risks and benefits of these management options, framing
them within the patient’s expectations of symptom relief
• Collaborate with the patient’s medical oncology team to maximize her quality of life by ensuring that they
understand her menopause symptoms and how they are managed
21
Speakers’ Abstracts & Learning Objectives (continued)
Plenary Symposium #7
“Addressing the Needs of Midlife Women Through & Beyond Breast Cancer”
Supported in part by grant funding from Pharmavite LLC
Mobility of Life: Skeletal Concerns
Ann E. Kearns, MD, PhD. Division of Endocrinology, Mayo Clinic,
Rochester, MN
The superiority of third generation aromatase inhibitors over tamoxifen as
adjuvant hormonal therapy in postmenopausal women with hormonal receptor
positive breast cancer has resulted in improved disease-free survival. The
randomized trials unexpectedly showed an association of arthralgia and
myalgia with aromatase inhibitors. This symptom complex is common and
can be significant enough to affect quality of life. Discontinuation of therapy
for this reason is not uncommon. The symptoms abate when the medication
is stopped and permanent joint destruction does not occur. There is no proven
treatment intervention, but over the counter pain relievers and physical
therapy may be helpful. The mechanism by which aromatase inhibitors cause
arthralgia and myalgia is not well understood. In contrast, it is understood
that the estrogen deprivation caused by aromatase inhibitors is the mechanism
underlying the known negative impact on bone mass. Managing the bone
health in postmenopausal women with breast cancer being treated with
aromatase inhibitors is important for long-term health. There are trials with
bisphosphonates that demonstrate efficacy in preventing the bone loss in
patients receiving aromatase inhibitors. Women receiving aromatase
inhibitors should have screening bone density and fracture risk assessment.
Those at intermediate risk may be considered for preventative therapy. In all
women receiving aromatase inhibitors, bone density should be monitored and
fracture risk reviewed. Understanding and managing the arthralgias and
skeletal consequences of aromatase inhibitors is important to optimal long
term health outcomes in women being treated with aromatase inhibitors.
Learning Objectives:
At the conclusion of this presentation, participants should be able to:
• R
ecognize the syndrome of aromatase inhibitor-associated arthralgia and myalgia, as well as identify and
select among the management options
• Identify and explain the bone loss induced by aromatase inhibitors and select patients for appropriate
treatment to ameliorate it
22
Plenary Symposium #8
“Osteoporosis Update: Practical Guidance for the Care of Postmenopausal Women”
Supported in part by grant funding from Amgen Inc., Eli Lilly and Company,
Merck & Co., Inc., and Warner Chilcott
Secondary Causes of Osteoporosis: When & How to Investigate
Steven T. Harris, MD, FACP. University of California, San Francisco, San
Francisco, CA
It is common for a low bone mineral density (BMD) to be interpreted as
“osteoporosis,” but the BMD can only provide an estimate of bone mineral
content (BMC), without establishing a specific underlying cause. A BMD
with a T-score of -2.5 or lower is consistent with primary osteoporosis, but is
not diagnostic of primary osteoporosis. It can be challenging to distinguish
between primary osteoporosis due to postmenopausal or age-related changes,
secondary osteoporosis due to other diseases or medications, osteomalacia,
and other disorders such as osteogenesis imperfecta. There are dozens of
diseases, conditions and drugs that have been associated with low BMD.
Many should be obvious from the medical history and physical exam, but
some are more subtle or detectable only by judicious laboratory testing. As a
general rule, every patient with low BMD deserves at least a limited
laboratory evaluation before initiating pharmacologic therapy. In several
series, roughly 40% to 60% of patients with apparent primary osteoporosis
had a previously unsuspected underlying disorder. In the absence of clear
national guidelines regarding laboratory evaluation, a consensus among expert
clinicians is that testing should/could include a complete blood count, comprehensive metabolic panel, 25-hydroxyvitamin D and a 24-hour urine
collection for the measurement of calcium excretion. Thyroid function tests
and other tests such as parathyroid hormone (PTH) should be done if
clinically indicated. Although there is room for debate about the extent of
laboratory testing, there is no debate that the cost of that baseline laboratory
testing is relatively small compared to the cost of many years of
pharmacologic therapy prescribed for the presumed underlying primary
osteoporosis. Although it is intuitively appealing to argue that secondary
causes of osteoporosis should be especially common in patients with BMDs
below normal for age (i.e., with abnormal BMD Z-scores), the available data
would suggest that that is not true. The most common laboratory abnormality
encountered in the evaluation of the patient with low BMD is vitamin D
deficiency. For some years, the target serum level for 25-hydroxyvitamin D
has been 30 ng/mL at a minimum. In late 2010, the Institute of Medicine
suggested that a blood level of 20 ng/mL or higher should suffice for the
general population. Nevertheless, many clinicians still feel that a level of 30
ng/mL or higher is desirable in an older patient with low BMD. In general, it
is recommended that adults up to age 70 receive 600 IU of vitamin D daily
and that those over age 70 receive 800 IU of vitamin D daily. Those
recommendations are based on bone health. It is also recognized, however,
that 1500 IU to 2000 IU of vitamin D daily may be required to consistently
raise the blood level of 25-hydroxyvitamin D above the target of 30 ng/mL.
The Institute of Medicine set the Tolerable Upper Intake Level of vitamin D
as 4000 IU daily. The Institute of Medicine also concluded that there is no
conclusive evidence linking a particular level of 25-hydroxyvitamin D to any
putative extra-skeletal benefit. There are no hard and fast rules regarding the
referral of patients to clinicians specializing in metabolic bone disease for the
further evaluation of possible secondary causes of bone disease. Broadly,
however, referral would be reasonable for: •Patients in whom the osteoporosis
is unexpectedly severe or has unusual features. Examples include
premenopausal women with low BMD, young men with low BMD, women
with unexpectedly low BMD despite long-term estrogen therapy, and patients
with fractures in the absence of major trauma despite normal BMD •Patients
with significant concurrent diseases that complicate management such as
malabsorption, hyperparathyroidism, Cushing’s disease or chronic renal
disease •Patients with statistically-significant bone loss or recurrent fractures
despite bone-protective therapy
Learning Objectives:
At the conclusion of this presentation, participants should be able to:
• C
ounsel peri- and postmenopausal women on evidence-based levels of vitamin D and calcium intake for
optimal bone and overall health
• Recognize the need to test for bone mineral density and consider osteoporosis therapy initiation in
postmenopausal women with recent fractures and other risk factors for osteoporosis
• Explain when, why, and how to evaluate for secondary causes of osteoporosis in postmenopausal women
23
Speakers’ Abstracts & Learning Objectives (continued)
Plenary Symposium #8
“Osteoporosis Update: Practical Guidance for the Care of Postmenopausal Women”
Supported in part by grant funding from Amgen Inc., Eli Lilly and Company,
Merck & Co., Inc., and Warner Chilcott
Osteoporosis Treatments: What’s New and What’s Coming?
Robert Lindsay, MBChB, PhD, FRCP. Helen Hayes Hospital and Columbia
University, West Haverstraw, NY
Around the turn of the century there was a move away from estrogen therapy,
and a corresponding move toward the use of bone specific agents, primarily
bisphosphonates for the prevention of osteoporosis in relatively young
women. Recently, that has come under scrutiny with the occurrence of
unusual transverse fractures of the femoral shaft several centimeters below the
greater trochanter. The realization that many of these fractures were occurring
in women on bisphosphonates has led to an evaluation of the use of these
drugs in the long term. The use of tools to estimate risk of fracture (e.g. FRAX
may mitigate the problem, but the level of risk and the mechanism are still not
understood. It appears that for those at high risk of fracture, as ewell as those
who have already suffered a fracture, the benefits of intervention still outway
any potential risk by a considerable margin. Whether a similar problem occurs
with denosumab, the RANK-L inhibitor is not known, but it is worth noting
that estrogens, Calcitonin and raloxifene have not been incriminated. Novel
agents are in the development pipeline, but face challenges, not only with the
development process and the need for fracture data, but also the increasing
number of generic agents that will be available. Alternative routes of
administration for teriparatide and calcitonin are under study. One estrogen
product has been combined with a tissue selective estrogen (CEE +
bazodoxifene). Analogues of teriparatide are being evaluated. In addition new
targets such as sclerostin and cathepsin K appear amenable to inhibition with
increased bone formation and inhibition of bone resorption resulting
respectively. It may be at least another 4-5 years before either reaches the
market. At present prescriptions continue to decline and it is clear that fracture
patient are still not being evaluated or treated. Perhaps the best chance for
improvement in management of osteoporosis is the development of guidances
(and stronger!) from NCQA, JCAHO, AMA supported by organizations such
as NOF, ASBMR and NAMS. This is somewhat of a carrot and stick
approach, and might be obviated if HCPs realized that all fractures in
postmenopausal women are potentially related to a compromised skeleton
and evaluated fracture patients accordingly.
Learning Objectives:
At the conclusion of this presentation, participants should be able to:
• Describe the relative strengths and drawbacks of available and investigational osteoporosis therapies
• Select among osteoporosis therapies to meet postmenopausal women’s individual needs
24
Plenary Symposium #9
“Androgens & Women’s Health”
Supported by grant funding from BioSante Pharmaceuticals, Inc.
Androgens in Women: Beyond Libido
Gail A. Laughlin, PhD. Department of Family & Preventive Medicine,
University of California, San Diego School of Medicine, San Diego, CA
Many studies have investigated the role of estrogen in cardiovascular disease
(CVD) in women; less attention has been paid to testosterone. The
testosterone-estrogen balance in women increases dramatically at menopause,
a time when central adiposity and the incidence of cardiovascular disease also
increase, suggesting that higher levels of testosterone relative to estradiol may
be atherogenic in women. The combination of hyperandrogenemia, an
adverse CHD risk profile and endothelial dysfunction in young women with
polycystic ovarian syndrome (PCOS) supports the view that androgen excess
may harm the female heart. However, the expected increase in CHD events
and mortality in women with PCOS has not been observed and recent studies
report low levels of testosterone in women with atherosclerotic disease,
raising the possibility that testosterone may have beneficial effects on the
heart, or suggesting a U-shaped association with suboptimal levels at both
extremes. The limited availability of sensitive and accurate assays for female
testosterone levels has impeded resolution of whether testosterone increases
or decreases the risk of CHD in older women. In addition, the association
may depend on the fraction of testosterone examined, the estrogen milieu,
and obesity and obesity-related factors. In contrast to estrogen, the
postmenopausal ovary continues to secrete androgens, contributing about
40% of circulating testosterone. Testosterone and estradiol circulate bound
to albumin, to sex hormone binding globulin (SHBG), and in the free
(unbound) state. The free and non-SHBG bound fractions are widely believed
to be the most bioactive forms, although direct evidence supporting this thesis
is sparse. An important difference in total and bioavailable (non-SHBG
bound) testosterone (BioT) is that the relative proportion of the bioavailable
fraction can be metabolically regulated. Central obesity and insulin resistance
have strong inhibitory influences on hepatic SHBG production, leading to
higher circulating levels of bioavailable testosterone (and estradiol).
Epidemiological evidence suggests that total and bioavailable testosterone
have opposing associations with some CVD risk factors and outcomes (higher
total T is beneficial, higher BioT is harmful) and that higher levels of
testosterone relative to estradiol are favorably associated with CVD risk
factors and CVD events. Testosterone may influence the development of CVD
in postmenopausal women via multiple pathways including effects on
adiposity, body fat distribution, and obesity-related molecules; effects on other
classic CVD risk factors; and/or direct effects on the vasculature.
Learning Objectives:
At the conclusion of this presentation, participants should be able to:
• D
escribe the physiologic changes in endogenous androgens across the menopausal transition and
during postmenopausal aging
• Draw on current understanding of the cardiometabolic effects of endogenous androgens to counsel
postmenopausal women on their possible role in cardiometabolic health and disease
25
Speakers’ Abstracts & Learning Objectives (continued)
Plenary Symposium #9
“Androgens & Women’s Health”
Supported by grant funding from BioSante Pharmaceuticals, Inc.
Androgen Treatment of Female Sexual Dysfunction: Risks, Benefits &
Available Therapies
Susan R. Davis, MBBS, FRACP, PhD. School of Public Health & Preventive
Medicine, Monash University, Melbourne, VIC, Australia
Androgens are vital hormones in women, circulating in concentrations
ranging from nanomolar to micromolar. Not only are androgens the precursor
hormones for estrogen biosynthesis in the ovaries and extragonadal tissues,
but androgens act directly via androgen receptors throughout the body.
Androgen levels decline with age in women with the greatest fall in total and
free testosterone occurring before the menopause(1). Large RCTs involving
naturally and surgically postmenopausal women presenting with hypoactive
sexual desire disorder (HSDD) demonstrate that testosterone therapy,
with/without concurrent estrogen therapy, improves the quality of the sexual
experience. More recent studies demonstrate the use of testosterone therapy
improve sexual wellbeing in premenopausal women with HSDD. The effects
appear not to be mediated by aromatization of testosterone to estrogen. The
other potential benefits of testosterone in women include favorable effects on
bone density, muscle mass, vascular endothelial function and cognitive
function. Despite the entrenched belief that higher blood levels of testosterone
increase the risk of cardiovascular disease (CVD), data from recent
observational studies mostly show an inverse relationship between
testosterone and CVD risk. Published randomized controlled trials (RCTs)
indicate that non oral testosterone therapy does not adversely affect plasma
lipids or other CVD risk markers (2, 3). One pilot RCT suggests favorable
effects of non oral testosterone treatment of women with established
congestive cardiac failure which merits further evaluation. Virilization is dose
dependent with few women discontinuing therapy in RCTs due to acne or
hirsutism(4). Preliminary data indicate favorable effects on cognition. The
relationship between endogenous testosterone production and breast cancer
risk remains contentious, with recent studies indicating no relationship (5). No
RCT of testosterone therapy has been sufficiently large or of sufficient
duration to establish whether such treatment may influence breast cancer
occurrence. There does not appear to be an association between testosterone
and endometrial cancer, or other malignancies on review of published studies.
Testosterone use has not been approved other than for surgically menopausal
women on estrogen therapy in Europe. Despite this, the use of testosterone by
women is widespread, with vast numbers of women using testosterone
preparations developed and marketed for men, testosterone preparations
compounded on individual prescriptions as oral lozenges and creams, and
testosterone implants. Hence there is a clear need for a testosterone therapy
delivering an appropriate female dose to be approved, so that women have
the option of using a product formulated for women.
Learning Objectives:
At the conclusion of this presentation, participants should be able to:
• Recognize the potential impact of androgens on sexual function
• S ummarize and compare the evidence-based efficacy and safety profiles of androgen treatment options for female sexual
dysfunction
26
“New Clinically Relevant Findings from the
MsFLASH Research Network: The Escitalopram Trial”
New Clinically Relevant Findings from the MsFLASH Research
Network: The Escitalopram Trial
A.Z. LaCroix, PhD1, E.W. Freeman, PhD2, K.E. Ensrud, MD, MPH3, S.D.
Reed, MD, MPH4, J.S. Carpenter, PhD, RN, FAAN5. 1Public Health Sciences
Division, Fred Hutchinson Cancer Research Center, Seattle, WA;
2
Departments of Obstetrics/Gynecology and Psychiatry, University of
Pennsylvania School of Medicine, Philadelphia, PA; 3VA Medical
Center/University of Minnesota, Minneapolis, MN; 4University of
Washington School of Medicine, Seattle, WA; 5School of Nursing, Indiana
University, Indianapolis, IN
The Menopause Strategies: Finding Lasting Answers for Symptoms and
Health (MsFLASH) clinical trials network, supported by the National
Institute on Aging as a cooperative agreement, is conducting a series of
randomized clinical trials designed to test new interventions for menopausal
symptoms. Our first randomized trial of escitalopram in healthy menopausal
women with hot flashes found that treatment significantly reduced the
frequency, severity, and bother of vasomotor symptoms during 8 weeks of
treatment. Delving further into the effects of escitalopram on vasomotor
symptoms, we then examined the efficacy of escitalopram compared with
placebo for: (1) daytime and nighttime hot flash frequency, severity, and
bother; (2) number of flash-free days and nights; and (3) hot flash interference
(the Hot Flash Related Daily Interference Scale). Escitalopram significantly
reduced both daytime (18%; p=0.001) and nighttime (15%; p=0.003) hot
flashes compared to placebo. The escitalopram group experienced about
one-half more flash-free day (p=0.03) and one-half more flash-free night
(p=0.001) compared to the placebo group. Hot flash interference scores
were reduced by 18.1 points in the escitalopram group compared to 14.6
points in the placebo group over the course of the trial (p=0.01). Despite
these encouraging findings, concerns about the use of SSRIs for hot flashes
include potential side effects, especially related to insomnia and sexual
function. Further evaluation of the effect of escitalopram versus placebo on
insomnia symptoms (Insomnia Severity Index) and subjective sleep quality
(Pittsburgh Sleep Quality Index) revealed that escitalopram at 10-20 mg/day
compared with placebo reduced insomnia symptoms and improved
subjective sleep quality at 4 and 8 weeks of follow-up (p≤0.001 for overall
treatment effect for both sleep measures). Escitalopram did not significantly
impact the overall Female Sexual Function Index, or a single item from the
Female Sexual Distress Scale, although escitalopram decreased lubrication
relative to placebo (-0.6 points difference on a 6-point scale; p=0.02) in
sexually active women. We conclude that escitalopram provides relief for
vasomotor symptoms, does not increase symptoms of insomnia, and does
not affect overall sexual function in non-depressed women with bothersome
hot flashes. Future MsFLASH trials will test several other therapies for
relief of menopause symptoms including yoga, aerobic exercise, omega-3 fatty
acid supplementation, low-dose estrogen, and venlafaxine using designs that
allow for side-by-side comparison of treatment effects relative to placebo
and/or comparison groups.
Learning Objectives:
At the conclusion of this presentation, participants should be able to:
• D
escribe the effects of escitalopram on vasomotor symptoms (frequency, severity, bothersomeness,
daytime hot flashes, nighttime hot flashes, hot flash interference), symptoms of insomnia, and sexual
function in nondepressed women with bothersome hot flashes
• Understand the future trials that will be conducted by the MsFLASH clinical trials network using factorial and
comparative effectiveness trial designs
27
Speakers’ Abstracts & Learning Objectives (continued)
Kenneth W. Kleinman Endowed Lecture
The Role of Genetic Testing & Genetic Information in Research
Thomas H. Murray, PhD. The Hastings Center, Garrison, NY
Spurred in part by Congressional interest in the implications of genetics, the
US Human Genome Project early on established an Ethical, Legal and Social
Implications (ELSI) Program. The ELSI Working Group consulted with many
clinicians, scientists, scholars, advocates and patient organizations in an effort
to learn what most concerned people about mapping and sequencing the
human genome. Two themes quickly emerged: worries that the privacy of
genetic information would be violated, and concerns that genetic information
would be used to discriminate against individuals believed to carry genetic
risks. The ELSI program established a Task Force on Genetic Information
and Insurance, which I chaired. The story of that Task Force carries valuable
lessons for clinicians, researchers and policy makers today. In particular,
claims about the power of genetic information to predict an individual’s life
course were based on a scientifically unjustified belief in genetic determinism.
That belief resulted in policy recommendations that tried to treat genetic
information as distinct from and more important than other forms of health
related information—a stance now known as genetic exceptionalism.
Demystifying genetic information, and reassuring clinicians, patients and
research subjects that it is not as powerful or predictive in most cases as had
been feared (or hoped) can facilitate genetic research and help clinicians
provide better counseling and care for their patients.
Learning Objectives:
At the conclusion of this presentation, participants should be able to:
• Explain the concept of genetic exceptionalism and provide a critical assessment of it
• Evaluate the implications of genetic risk information for health insurance systems
• Accurately appraise for patients and research subjects the risks of genetic discrimination and violations of genetic privacy
28
& County of San Francisco, Trainer, Office for Victims of Crime, Training &
Technical Assistance Center, University of California, Hastings College, San
Bruno, CA
The extent of elder abuse is largely unknown due to the varying degrees of
cognitive and physical abilities of older persons, research design limitations,
and inconsistent definitions among the experts or in publications. However,
most agree that elder abuse, neglect and exploitation of older females may
include physical abuse, rape, sexual abuse, emotional or psychological abuse,
neglect, and financial exploitation where the cost to older persons and society
is greater than $2.9 billion. It is also known that older women experience
sexual, domestic
Plenary Symposium
#10and financial victimization often committed by persons in
trusted and ongoing relationships. In 2010, researchers found that when
cognitively capable, the prevalence rate of victimization in persons over 60
“Abuse, Neglect, & Exploitation
ofage
the
Older
years of
is 11.4%,
andFemale:
that 65% of reported victims were women. The
prevalence of partner
violence is 26.5% and includes physical and
Integrating Healthcare, Legal,lifetime
&
Community
Responses”
sexual violence which are seriously underreported. Low rates of reporting are
associated with family dynamics and values, inability to report, disbelief, and
lack of awareness that the abusive conduct should be reported. Risk
assessments of the older female that evaluate the patient’s ability to
understand and exercise informed consent, respecting the patient’s rights to
autonomy and self-determination, explore the relationships between family
Abuse, Neglect, & Exploitation of the Older Female: Integrating
members and neighbors (which may include the abuser), drug and alcohol
Healthcare, Legal, & Community Responses
use, and the belief that respect for self determination using the least restrictive
Patricia M. Speck, DNSc, APN, FNP-BC, DF-IAFN, FAAFS, FAAN1,
alternatives are characteristics of a thorough health care evaluation that should
Candace J. Heisler, JD2. 1University of Tennessee Health Sciences Center
be completed at every visit. Health care providers must be familiar with local
College of Nursing, Memphis, TN; 2Assistant District Attorney for the City
community agencies available to assist when abuse, neglect and exploitation
& County of San Francisco, Trainer, Office for Victims of Crime, Training &
are suspected or confirmed, including agencies that support safe havens and
Technical Assistance Center, University of California, Hastings College, San
medical treatment of the older person’s ills. The failure of the health care
Bruno, CA
provider to take an active role may subject the vulnerable older woman to
continued violence and exploitation. The impact to those exposed to
The extent of elder abuse is largely unknown due to the varying degrees of
significant childhood or a lifetime of abuse is correlated to diseases that affect
cognitive and physical abilities of older persons, research design limitations,
every biological system and has been shown to contribute to premature death
and inconsistent definitions among the experts or in publications. However,
by as much as 20 years! When older women seek care for vague somatic
most agree that elder abuse, neglect and exploitation of older females may
complaints or when there are implausible explanations for physical trauma,
include physical abuse, rape, sexual abuse, emotional or psychological abuse,
health care providers have the opportunity to identify, evaluate, and refer
neglect, and financial exploitation where the cost to older persons and society
individual victims to specialized care and interventions. That said, research
is greater than $2.9 billion. It is also known that older women experience
reveals that health care providers are ill equipped to identify or manage the
sexual, domestic and financial victimization often committed by persons in
older woman’s needs or the system’s response to the non-medical needs
trusted and ongoing relationships. In 2010, researchers found that when
following abuse, neglect or exploitation. Through case studies of typical
cognitively capable, the prevalence rate of victimization in persons over 60
scenarios following sexual or domestic abuse, neglect or exploitation in the
years of age is 11.4%, and that 65% of reported victims were women. The
older female, this presentation will review the epidemiological data, explain
lifetime prevalence of partner violence is 26.5% and includes physical and
the coordinated community response, identify stakeholder agencies, clarify
sexual violence which are seriously underreported. Low rates of reporting are
legal reporting requirements, and discuss common approaches to the ideal
associated with family dynamics and values, inability to report, disbelief, and
health care provider response of forensic medical management and criminal
lack of awareness that the abusive conduct should be reported. Risk
justice obligations.
assessments of the older female that evaluate the patient’s ability to
understand and exercise informed consent, respecting the patient’s rights to
autonomy and self-determination, explore the relationships between family
members and neighbors (which may include the abuser), drug and alcohol
use, and the belief that respect for self determination using the least restrictive
alternatives are characteristics of a thorough health care evaluation that should
be completed at every visit. Health care providers must be familiar with local
community agencies available to assist when abuse, neglect and exploitation
are suspected or confirmed, including agencies that support safe havens and
medical treatment of the older person’s ills. The failure of the health care
provider to take an active role may subject the vulnerable older woman to
continued violence and exploitation. The impact to those exposed to
significant childhood or a lifetime of abuse is correlated to diseases that affect
every biological system and has been shown to contribute to premature death
by as much as 20 years! When older women seek care for vague somatic
complaints or when there are implausible explanations for physical trauma,
health care providers have the opportunity to identify, evaluate, and refer
individual victims to specialized care and interventions. That said, research
reveals that health care providers are ill equipped to identify or manage the
older woman’s needs or the system’s response to the non-medical needs
following abuse, neglect or exploitation. Through case studies of typical
scenarios following sexual or domestic abuse, neglect or exploitation in the
older female, this presentation will review the epidemiological data, explain
the coordinated community response, identify stakeholder agencies, clarify
legal reporting requirements, and discuss common approaches to the ideal
health care
provider response of forensic medical management and criminal
Learning
Objectives:
justice obligations.
At the conclusion of this presentation, participants should be able to:
•
•
•
•
•
Describe the epidemiology of and latest research addressing abuse, neglect, and exploitation of older/vulnerable persons
Explain the role of coordinated community response, members and roles, and community impact
Discuss the elements of a forensic evaluation of domestic and sexual violence involving the older female
Clarify legal reporting requirements for older/vulnerable person abuse, neglect, and exploitation
Identify common presentations of older/vulnerable person abuse, neglect, and exploitation
29
Speakers’ Abstracts & Learning Objectives (continued)
Plenary Symposium #11
“The Mind-Body Connection: Impact on Health & Disease”
A Healthy Midlife Crisis – Habits That Lead to Wellness
Patricia J. Sulak, MD. Scott & White Healthcare, Texas A&M College of
Medicine, Temple, TX
Despite the numerous life-saving advances in medicine from improved
diagnostic testing to miracle medications to surgical wonders, our waiting
rooms are filled with women who are not healthy, not happy, and even
depressed, often with numerous self-induced medical conditions. Many are
complicating their lives and harming their well being with numerous
unhealthy behaviors including a sedentary lifestyle, dietary indiscretion,
substance abuse, and self-induced stress. These health risk behaviors can lead
to the #l overall killer (cardiovascular disease) and the #l cancer killer (lung
cancer). Then comes the dreaded “midlife crisis”. It’s a fact - - as we age, our
body wants to deteriorate and atrophy. But, the good news is that we can delay
the decay for many years. Another fact - - most disease states can be improved
and sometimes even prevented with a healthy lifestyle. The problem is two
fold. Number one: What is healthy? With the promotion of miracle
supplements, weight loss wonder programs, and even colonics, what is safe,
no less healthy? Number two: How do I institute healthy habits and,
importantly, maintain them? Healthcare professionals and patients need the
facts on components of a healthy lifestyle that can improve the quality and
quantity of their lives. What are some of these lifesaving habits? First and
foremost, make movement mandatory. With our technologically advanced
society, we have become too sedentary necessitating that we become creative
in finding enjoyable ways to put healthy movement into our daily lives. The
American Heart Association has established guidelines for reducing risk of
chronic disease and preventing weight gain. Secondly, critique caloric
consumption. While many diets are promoted as the answer, the
Mediterranean Diet has been the most studied in terms of disease prevention.
Other healthy habits to be discussed include addressing addictions, managing
time and money, the power of forgiveness, and spiritual connection.
Learning Objectives:
At the conclusion of this presentation, participants should be able to:
• State the WHO definition of health
• List dietary and exercise guidelines that prevent disease
• Recognize and prescribe lifestyle modifications that foster health and happiness
30
Plenary Symposium #11
“The Mind-Body Connection: Impact on Health & Disease”
A Mindful Midlife—Understanding the Mind-Body Connection
Herbert Benson, MD. Harvard Medical School, Boston, MA
Stress plays an important role throughout a person’s life. It is related to 6090% of visits to health care professionals. The relaxation response (RR) is
the counterpart of the stress or fight-or-flight response. The RR is
characterized by decreased oxygen consumption, carbon dioxide elimination,
and respiratory rate as well as decreased limbic system activity and
responsivity to plasma norepinephrine. There are coordinated genetic
expression changes in the RR that are opposite to those of the stress response.
The genetic changes of the RR are characterized by decreases in oxidative
phosphoralization (energy metabolism), inflammation activity as well as
apoptotic expression. To the extent that disorders are caused or exacerbated
by stress, regular elicitation of the RR is an effective therapeutic intervention.
These conditions include: premenstrual syndrome, hot flashes of menopause,
infertility, hypertension, depression, anxiety, insomnia, irritable bowel
syndrome, inflammatory bowel disease, and rheumatoid arthritis as well as
other autoimmune conditions. Two steps are usually practiced to evoke the
RR: (1) the repetition of a word, sound, prayer, or physical activity and (2) the
disregard of everyday thoughts with a return to the repetition. The two steps
break the train of everyday thinking and are linked to millennia old practices
that include meditation, yoga, repetitive prayer, tai chi and chi gong. Regular
use of the relaxation response is coordinated with appropriate pharmaceutical
and surgical therapies. It is an essential feature of self-care that includes
nutrition and exercise.
Learning Objectives:
At the conclusion of this presentation, participants should be able to:
• Describe the physiology of the relaxation response
• Identify methods/strategies that elicit the relaxation response
• Demonstrate the role of mind/body medicine with regard to managing menopausal symptoms and stress
31
NAMS11_Regular-LB_Abstracts-2 8/29/11 4:13 PM Page 1
Scientific Sessions
PLENARY SCIENTIFIC ABSTRACT SESSION #1
S-1.
The Effects of Bazedoxifene/Conjugated Estrogens on Breast Density in
Postmenopausal Women
Jennifer A. Harvey1, JoAnn V. Pinkerton2, Kaijie Pan3, John R. Thompson3, Sebastian
Mirkin3, Arkadi A. Chines3. 1Department of Radiology, University of Virginia Health
System, Charlottesville, VA; 2Department of Obstetrics and Gynecology, Division of
Midlife Health, University of Virginia Health System, Charlottesville, VA; 3Pfizer Inc,
Collegeville, PA
Objective: Increased mammographic breast density may be a risk factor for breast cancer,
but the etiology of this relationship is not well understood. Certain medications, including
combined estrogen/progestin therapy, have been shown to increase breast density.
Published phase 3 studies have demonstrated the efficacy and safety of
bazedoxifene/conjugated estrogens (BZA/CE), a tissue selective estrogen complex
(TSEC), in the treatment of menopausal symptoms and prevention of postmenopausal
osteoporosis without an increase in breast pain or breast cancer. The effects of BZA/CE
on breast density were evaluated in a substudy of the Selective estrogens, Menopause,
And Response to Therapy (SMART)-5 trial. Design: In this phase 3, double-blind,
placebo (PBO)-controlled study of postmenopausal women with a uterus (N = 1,843),
subjects were randomized to receive BZA 20 mg/CE 0.45 or 0.625 mg, BZA 20 mg, CE
0.45 mg/medroxyprogesterone acetate (MPA) 1.5 mg, or PBO daily for 12 months to
evaluate efficacy and safety. A subset of these women met inclusion criteria and were
enrolled in a breast density substudy. Breast density changes were assessed by digitized
mammograms that were centrally read by a single radiologist using specifically developed
software. Comparison of the adjusted mean difference in percent breast density at 12
months for each group versus PBO was based on a non-inferiority test with a pre-defined
margin of 1.5%. Results: A total of 940 women (mean age ± standard deviation (SD), 54.0
± 4.0 y; mean years since last menstrual period, 4.4 ± 3.6 y) participated in the breast
density substudy: BZA 20 mg/CE 0.45 mg (n = 231), BZA 20 mg/CE 0.625 mg (n =
247), BZA 20 mg (n = 122), CE 0.45 mg/MPA 1.5 mg (n = 100), or PBO (n = 240). At
12 months (Figure), BZA 20 mg/CE 0.45 and 0.625 mg demonstrated non-inferiority
versus PBO (the upper bound of the 95% confidence interval [CI] was 0.51% and 0.44%,
respectively). However, CE 0.45 mg/MPA 1.5 mg showed a significant increase in mean
percent breast density at 12 months versus PBO (P <0.001; upper bound of the 95% CI,
2.7%). Conclusion: Women treated with BZA 20 mg/CE 0.45 or 0.625 mg for 12 months
showed no differences in breast density compared with those treated with PBO, suggesting
a potential advantage of BZA/CE over conventional estrogen/progestin therapy.
group when the results of WHI were announced are now 57-73 years of age and thus at
greater risk for cardiovascular and other chronic disease. This group started HT at the
normal age of menopause, unlike two thirds of the women in the WHI study(1). Design:
The aim of this retrospective cohort study was to test differences in the incidence of
obesity, hypertension, and hyperlipidemia, as well as the use of medications among
women ages 57 to 73 who used HT for at least 5 years and subsequently stopped its use
compared to those who continued HT use. The study also assessed quality of life and
medical morbidity. The study enrolled women born between 4/1/1938 and 3/31/1953 who
previously used HT for at least five years. Recruitment is ongoing; to date 250 women
have been enrolled of which 209 are considered complete. Interviews and measurements
were conducted at doctors’ offices in the New York City area. Three groups were
compared: women who have remained on HT (“Continued HT,” n= 101), women who
discontinued HT use for a minimum of 6 months and have since resumed HT(“Resumed
HT”, n=33), and women who discontinued HT and have not resumed its
use(”Discontinued HT,” n=75). Results: Of the women who discontinued HT, 67% cited
adverse media as a reason for discontinuation, 29% cited a physician’s recommendation,
and 11% stated other reasons. The overall mean age at interview was 64.8±4.0 years. The
Discontinued HT group was slightly older than the Continued HT group; 65.7±3.9 vs.
64.1±4.0 years (p<.05) but similar to the Resumed HT group (65.1±4.0 years, n.s.). 95%
were Caucasian, and 87% had a college education or greater. Patients started HT at
49.2±5.0 years. Mean weight was 63.2±11.2 kg and mean body mass index (BMI) was
23.8±4.2. No differences were noted between the groups with respect to weight, height,
BMI, waist/hip ratio, blood pressure, triglycerides or cholesterol levels. Women on HT
(Continued HT and Resumed HT) scored higher than the Discontinued HT group on the
115 point Utian Quality of Life scale (87.7±13.3 vs. 81.8±13.3, p<.01). In particular,
women on HT scored higher than the Discontinued HT group on the 35 point occupational
satisfaction scale subset (26.5±7.2 vs. 23.5±7.8, p<.02). The Discontinued HT group
scored higher than those on HT with respect to the Greene climacteric vasomotor scale
(1.2±1.4 vs. 0.7±1.1, p<.02). Vaginal dryness was also greater (1.9±1.1 vs. 1.4±0.6,
p<<.001). Finally, the Discontinued HT group was on significantly more antihypertensive
medications (29.9% of the Discontinued HT group vs. 15.9% of Continued HT group
and 6.5% of Resumed HT group). Combining the groups on HT, 13.8% of women
currently on HT were on antihypertensive medications compared with 29.9% of women
not on HT (p<.01). Conclusion: These results suggest that discontinuation of HT may
place some women at risk for the development of hypertension, which may be an early
indication of the metabolic syndrome and those remaining on HT score higher on scale
of quality of life, particularly that which focuses on satisfaction with profession and
occupation. REFERENCES: 1. Rossouw, JAMA 2002, 2. Grady, Obstet Gynecol 2003,
3. IMS Health, WSJ 2006
S-3.
Hot flashes and lipids in the Study of Women’s Health Across the Nation
Figure. Mean Adjusted Difference (95% CI) in Percent Breast Density Versus
Placebo at 12 Months.
S-2.
Effect of Estrogen and Hormone Therapy Withdrawal on Health and
Quality of Life after Publication of The Women’s Health Initiative in New
York City
Michelle Warren, Olivia Richardson, Sonal Chaudhry, MD, Aimee Shu, MD, Abigail
Chua, Nancy L. Sloan, DrPH, MPH. Ob/Gyn, Columbia University Medical Center, New
York, NY
Objective: Since July of 2002, when the results of the Women’s Health Initiative (WHI)
were published, a large number of women stopped hormone therapy (HT) due to concerns
over risks of heart attacks and breast cancer(1). This sudden discontinuation of therapy is
probably the largest single decrease of a medication over a short period of time in the
history of American medicine. The initial drop in sales amounted to 33% and has
continued at rate of approximately 6% a year(2;3). These events represent an unparalleled
opportunity to answer questions of risk and benefit in women who initiated therapy at
menopause and subsequently chose to stop therapy. Evidence exists that the
hypoestrogenic menopausal state is associated with weight gain and changes in body
composition. Such changes increase visceral fat and the secretion of inflammatory factors
and predispose women to chronic diseases such as diabetes, heart disease and the
metabolic syndrome. The time elapsed since 2002 presents an appropriate interval for
observation of the consequences of this experience, as women who were in the 49-64 age
32
Rebecca C. Thurston, PhD1,2, Samar R. El Khoudary, PhD2, Kim Sutton-Tyrrell, DrPH2,
Carolyn Crandall3, Ellen Gold4, Barbara Sternfeld5, Hadine Joffe, MD, MSc6, Karen A.
Matthews, PhD1,2. 1Psychiatry, University of Pittsburgh, Pittsburgh, PA; 2Epidemiology,
University of Pittsburgh, Pittsburgh, PA; 3Medicine, University of California, Los Angeles,
Los Angeles, CA; 4Public Health Sciences, University of California, Davis, Davis, CA;
5
Research, Kaiser Permanente, Oakland, CA; 6Psychiatry, Harvard, Boston, MA
Objective: Vasomotor symptoms, or hot flashes (HF) and night sweats (NS), reported by
75% of peri- and postmenopausal women, are thought to have quality of life, but few
medical, implications. However, recent findings link HF to cardiovascular disease (CVD)
risk. The reasons for these associations are not fully understood, but evidence suggests that
HF may be associated with an adverse lipid profile. Our aim was to examine the relations
between HF and lipids, controlling for other CVD risk factors, estradiol (E2), and follicle
stimulating hormone (FSH) over a 7 year period. Design: Participants were 3201 women
ages 42-52 years at baseline in the Study of Women’s Health Across the Nation (SWAN).
Participants at entry completed interviews (HF and NS: none, 1-5, ≥6 days in past 2
weeks; affect), physical measures (body mass index (BMI)), and a blood draw (low
density lipoprotein (LDL), high density lipoprotein (HDL), apolipoprotein(a) (apo(a)),
apolipoprotein(b) (apo(b)), lipoprotein(a) (Lp(a)), trigycerides, E2, FSH) at baseline and
approximately yearly for 7 years thereafter. HF were examined in relation to each lipid
with covariates age; site; race/ethnicity; education; BMI; menopausal status; parity;
alcohol use; smoking; physical activity; diabetes status; diagnosed cardiovascular disease;
depression/anxiety symptoms; and anti-hypertensive, anticoagulant, and lipid lowering
medication use. E2 and FSH were added in separate steps. Data from visits with reported
hormone therapy use were excluded. Results: In linear mixed models adjusted for all
covariates except hormones, more frequent HF were significantly associated with higher
levels of all of the lipids assessed except Lp(a): LDL [vs. no HF, 1-5 days: β
B(95%CI)=1.48(0.57-2.40, p=.002); ≥6 days: B(95%CI)=2.13(0.91-3.35, p=.0006)],
HDL [vs. no HF, 1-5 days: B(95%CI)=.30(-0.06-0.65, p=.10); ≥6 days:
B(95%CI)=.77(0.30-1.25, p=.001)], apo(a) [vs. no HF, 1-5 days: B(95%CI)=.92(-0.011.85, p=.05); ≥6 days: B(95%CI)=1.97(0.76-3.19, p=.002)], apo(b) [vs. no HF, 1-5 days:
B(95%CI)=1.41(0.61-2.20, p=.0006); ≥6 days: B(95%CI)=2.51(1.45-3.57, p<.0001)],
and triglycerides [(vs. no HF, 1-5 days: % change (95%CI)=2.91(1.41-4.43, p=.0001);
≥6 days: % change(95%CI)=5.90(3.86-7.97, p<.0001)]. These associations remained
significant for LDL, HDL, apo(a), apo(b), and triglycerides after adjustment for E2, and
for HDL, apo(a), apo(b), and triglycerides after adjustment for FSH. Findings for NS
were consistent with those for HF. Conclusion: HF were associated with higher LDL,
HDL, apo(a), apo(b), and triglycerides during a 7-year follow up period, controlling for
CVD risk factors and E2 concentrations. Lipids should be considered in examining links
between HF and CVD risk. SWAN has support from the NIH, DHHS, through NIA,
NINR and NIH ORWH (NR004061; AG012505, AG012535, AG012531, AG012539,
NAMS11_Regular-LB_Abstracts-2 8/29/11 4:13 PM Page 2
AG012546, AG012553, AG012554, AG012495). The content of this abstract is solely the
responsibility of the authors and does not necessarily represent the views of the NIA,
NINR, ORWH or NIH.
S-4.
Does Route of Administration for Estrogen Hormone Therapy and
Estradiol Transdermal System Dosage Strength Impact Risk of Venous
Thromboembolism
Kristijan H. Kahler, PhD, RPh1, Judit Nyirady, MD, MBA1, Eric Beresford, PharmD1,
François Laliberté2, Katherine Dea, MA2, Mei Sheng Duh, MPH ScD3, Patrick Lefebvre,
MA2. 1Novartis Pharmaceuticals Corporation, East Hanover, NJ; 2Groupe d’analyse, Ltee,
Montreal, QC, Canada; 3Analysis Group, Inc, Boston, MA
Objective: Hormone therapy (HT) is regularly used in the treatment of symptoms
associated with menopause, such as hot flashes and vulvovaginal atrophy. Venous
thromboembolism (VTE) is among the most serious complications associated with HT.
A recent study has showed that transdermal estrogen administration was associated with
a lower risk of VTE relative to oral estrogen administration. The objective of the current
follow-up analysis was to evaluate the impact of high dose estradiol transdermal system
(ETS; Vivelle-Dot®) on the risk of VTE events as compared to the use of oral estrogenonly HT agents. Design: A health insurance claims analysis was conducted using the
Thomson Reuters MarketScan database from January 2002 through October 2009.
Patients ≥35 years old with continuous insurance coverage, newly initiated on an ETS or
oral estrogen-only HT with ≥2 dispensings were analyzed. VTE was defined as ≥1
diagnosis code for deep vein thrombosis (DVT; ICD-9 codes: 451.1x, 451.2, 453.4x,
453.8, 453.9) or pulmonary embolism (PE; ICD-9 codes: 415.1x). Patients with a prior
history of VTE or using any estrogen HT agents within 180 days before the first ETS or
oral estrogen-only HT drug dispensing were excluded. The study observation period
started on the date of ETS or oral estrogen HT treatment initiation (index date) until 90
days following the index treatment interruption or discontinuation (i.e., continuous use of
therapy). Cohorts of ETS and oral estrogen-only HT were matched 1:1 based on both
exact factor and propensity score matching methods to ensure balanced patient
characteristics at baseline. The incidence rates of VTE events were calculated as number
of patients with an event divided by patient-years of observation, censored at the time of
the first event. The incidence rate ratio (IRR), assessed through Poisson regression was
used to compare the rates of VTE events for ETS relative to oral estrogen-only HT cohorts.
ETS dosage strength ranged from 0.025 to 0.1 mg/day. To assess the impact of ETS
dosage, IRRs of VTE were also reported for subgroups of women initiating high dose
ETS based on two definitions: (i) 0.075 or 0.1 mg/day and (ii) 0.1 mg/day, relative to their
corresponding matched oral estrogen-only HT users. Results: Among the 30,547 patients
treated with ETS and 159,281 receiving oral estrogen-only HT, 27,018 ETS users and an
equal number of oral estrogen-only HT users were matched to form the overall study
population. The mean ages of the matched cohorts (SD) were 48.9 (7.1) years; in each
cohort 6,044 (22.4%) and 1,788 (6.6%) patients had a hysterectomy and an oophorectomy
at baseline, respectively. The mean (median) drug exposure for the ETS and oral estrogenonly HT cohorts was 391 (264) and 401 (272) days, respectively. Based on the matched
analysis of the overall study population, a total of 115 ETS users developed VTE
compared to 164 subjects in the oral estrogen-only HT cohort (IRR: 0.72; 95% CI: 0.570.91, P=0.006). Furthermore, the lower risk for VTE events associated with ETS relative
to oral estrogen-only HT remained statistically significant in women initiating high dose
ETS. In the matched cohorts of ETS and estrogen-only HT users where ETS was initiated
at 0.075 or 0.1 mg/day (11,570 women in each cohort), 45 ETS users and 80 oral estrogenonly HT users developed VTE (IRR=0.58; 95% CI: 0.40-0.84, P=0.004), while in the
matched cohorts where high dose ETS was defined as 0.1 mg/day (8,956 patients in each
cohort), 32 ETS users and 65 oral estrogen-only HT users developed VTE (IRR=0.52;
95% CI: 0.34-0.80, P=0.003). Conclusion: This large population-based study of over
50,000 patients based on real-world data suggests that patients receiving ETS (VivelleDot®) have significant lower incidence of VTE of approx 30% compared to patients
receiving oral estrogen-only HT. Data from this study also showed that the lower risk for
VTE associated with ETS remained significant in women initiating high dose ETS relative
to matched oral estrogen-only HT women.
S-5.
Efficacy of a novel SERM, ospemifene, in the treatment of moderate-tosevere vaginal dryness symptoms of vulvovaginal atrophy associated with
menopause
David Portman, MD1, Gloria A. Bachmann, MD2, Steven R. Goldstein, MD, FACOG,
CCD, NCMP3, Vivian Lin4, James Liu5, Shelli Graham6, Michele Giliberti6, James A.
Simon, MD, CCD, NCMP, FACOG7. 1Columbus Center for Women’s Health Research,
Columbus, OH; 2UMDNJ -Robert Wood Johnson Medical School, New Brunswick, NJ;
3
New York University School of Medicine, New York, NY; 4QuatRX Pharmaceuticals
Company, Ann Arbor, MI; 5MacDonald Women’s Hospital, Cleveland, OH; 6Clinical
Development, Shionogi Inc., Florham Park, NJ; 7The George Washington University
School of Medicine, Washington, DC
Objective: Ospemifene, a novel, selective estrogen receptor modulator (SERM) that
exerts estrogenic, pharmacologic activity in the vaginal epithelium, is presently being
studied for treatment of symptoms of vulvovaginal atrophy (VVA) in postmenopausal
women. This study assessed the efficacy, safety and tolerability of ospemifene 60 mg/d
in the treatment of VVA symptoms. Design: A 12-wk, 1:1 randomized, double-blind,
placebo-controlled, parallel-group study enrolling 919 postmenopausal women 40 to 80
years of age with VVA in two strata based on their self-reported most bothersome
symptom (MBS) of vaginal dryness or vaginal pain (dyspareunia). Two study populations
were analyzed: the intent-to-treat (ITT) (primary analysis) and per protocol (PP). Subjects
in each stratum were randomized to receive 60 mg/d ospemifene or placebo and were
provided with a nonhormonal vaginal lubricant to use as needed (PRN). For each stratum,
changes from baseline to Wk 12 (LOCF) for the four co-primary endpoints were assessed:
vaginal pH, percentages of superficial cells and parabasal cells in the maturation index and
the severity of the MBS. This abstract reports the Dryness Stratum results. Results: In the
ITT analysis, at Wk 12 ospemifene demonstrated significant efficacy vs placebo for 3 of
4 co-primary endpoints from baseline. Significant mean changes from baseline to Wk 12
for vaginal pH and percentages of superficial (LS mean) and parabasal cells (Median)
were evident (Table 1). Significant improvement was observed as early as 4 wks.
Improved mean change was observed for the MBS vaginal dryness at Wk 12, which
approached statistical significance (P=0.0803). A higher % of subjects treated with
ospemifene reported no vaginal dryness, and the subjects’ self-reported symptom severity,
which was assessed on a 4-point scale improved by 2 to 3 points in 46.3% ospemifene vs
34.4% placebo subjects. The PP analysis showed statistically significant improvement
for all 4 co-primary endpoints (pH, % superficial and % parabasal cells, all P<0.0001 and
vaginal dryness, P=0.0143) and similar improvements in dryness severity. The main
difference between the ITT and the PP populations was in study drug compliance, which
was higher in the PP population. The numbers of subjects with ≥1 adverse event (AE) at
Wk 12 in both strata combined is summarized in Table 2. Discontinuation rates were
similar in the ospemifene (10.2%) and placebo (11.6%) groups. Endometrial histology
assessments showed no cases of hyperplasia and 2 (1.0%) cases of active proliferation in
the ospemifene group vs 0% in the placebo group. Vaginal bleeding was reported in 2
(0.4%) and 4 (0.9%) subjects in the ospemifene and placebo groups, respectively; 1
subject on ospemifene experienced deep vein thrombosis was discontinued from the study.
There were no cases of myocardial infarction, breast cancer or death. Conclusion: In
postmenopausal women with the self-reported MBS of vaginal dryness, these data
demonstrate that treatment with ospemifene 60 mg/d provides clinically and statistically
significant efficacy and was well tolerated. With greater improvement in symptom severity
scale changes and in markers of vaginal health, this novel SERM may prove to be the
first non-estrogen to effectively treat the symptoms of VVA.
Table 1 Change from BL to Wk 12 LOCF (ITT)*
* Similar results were reported for the PP analysis.
Table 2 Adverse Events
S-6.
Vasomotor Symptoms in Premenopausal Women by Race: the LEAVES
Study
Susan D. Reed, MD, MPH1,2, Katherine M. Newton, PhD3, Johanna Lampe, PhD2, Sharon
Fuller3, Congh Qu, PhD3, Gabrielle Gundersen, MS3. 1Obstetrics and Gynecology,
University of Washington, Seattle, WA; 2Public Health Sciences, Fred Hutchinson Cancer
Research Center, Seattle, WA; 3Group Health Research Institute, Seattle, WA
Objective: Prevalence of vasomotor symptoms among women over age 45 who report
regular periods have not been well described. Prevalence variability by race/ethnicity is
expected. Design: We performed a population-based mailed survey of 18,500 women,
ages 45-58, enrolled at Group Health Cooperative in Washington State, identified from
automated databases as not using hormones (50% response rate). The purpose of this
analysis was to describe self-reported hot flashes and night sweats, by race/ethnicity
among all premenopausal women surveyed who reported regular menses. We excluded
women who had had a bilateral salpingo-oophorectomy. Generalized linear models were
used to calculate differences in vasomotor symptoms by race, adjusted for age (*P<0.05;
†P<0.001). Results: There were 1,575 premenopausal women who responded to the
survey, 73% were white, the mean age was 48.5±2.5 years, 32% reported ever having hot
flashes and 48% reported ever having night sweats. Premenopausal native
Hawaiians/Pacific Islanders were most likely to report ever having hot flashes (46%),
followed by African American women (39%), American Indian (38%), Hispanic nonwhite
(37%), white (34%), Filipino (30%), Vietnamese (29%), Japanese (26%), Asian Indian
(22%), Chinese (19%), and Hispanic white (18%). Controlling for age, Chinese women
were 11% less likely to have ever had hot flashes as compared with white women
(P<0.01). Premenopausal American Indian women were most likely to report ever having
night sweats (62%), follow by African American (61%), white (51%), Hawaiian/Pacific
Islanders (46%), Hispanic nonwhite (41%), Hispanic white (35%), Japanese* and Asian
Indian (33%), Filipino* (30%), and Chinese† and Vietnamese* (24%). Conclusion:
Among women over age 45, who were most likely in the early to mid transition, Asian
women were least likely to report having hot flashes and night sweats. African-American
reported hot flashes and night sweats more commonly than white or Asian women.
33
NAMS11_Regular-LB_Abstracts-2 8/29/11 4:13 PM Page 3
Scientific Sessions (continued)
CONCURRENT SESSION #1
S-7.
Reproductive Safety of Bazedoxifene in Postmenopausal Women With
Osteoporosis: Results of a 7-year, Randomized, Placebo-controlled, Phase
3 Study
Santiago Palacios1, Tobie J. de Villiers2, Fiorenzo De Cicco - Nardone3, Amy Levine4,
Robert Williams4, Teresa Hines4, Arkadi A. Chines4. 1Instituto Palacios, Madrid, Spain;
2
Panorama MediClinic and University of Stellenbosch, Cape Town, South Africa;
3
Università Cattolica del Sacro Cuore, Rome, Italy; 4Pfizer Inc, Collegeville, PA
Objective: Endometrial and breast safety are important considerations in the development
of selective estrogen receptor modulators (SERMs). Bazedoxifene (BZA) has
demonstrated long-term safety and efficacy for the treatment of postmenopausal women
with osteoporosis in a pivotal phase 3 study. Here we describe the reproductive safety of
BZA in women enrolled in this study during 7 years of treatment. Design: In the 3-year
core study, generally healthy postmenopausal women with osteoporosis (N=7,492; mean
age, 66.4 y) were randomized to receive BZA 20 or 40 mg, raloxifene (RLX) 60 mg, or
placebo daily. All subjects were supplemented with elemental calcium (1,000-1,200 mg/d)
and vitamin D (400-800 IU/d). During a 2-year extension (N=4,216; Years 4 and 5), the
RLX 60-mg arm was discontinued, and subjects receiving BZA 40 mg were transitioned
to BZA 20 mg. The study remained double-blinded and was extended for an additional 2
years (Years 6 and 7; N=1,732). All subjects continued to receive BZA 20 mg or placebo.
Endometrial and breast safety findings at 7 years are reported for BZA 20 mg, BZA
combined (BZA 20-mg group plus the group that transitioned from BZA 40 to 20 mg
after 4 years), and placebo. Adverse events (AEs) were recorded throughout the study.
Endometrial thickness as measured by transvaginal ultrasound (TVU) at baseline and at
Year 7 is presented for subjects in the endometrial safety substudy. Results: Overall, the
reproductive safety findings with BZA at 7 years were favorable and generally consistent
with those seen at 3 and 5 years. Transvaginal ultrasound data were available for 90
subjects at baseline and at Year 7 (BZA 20 mg, n=31; BZA combined, n=61; placebo,
n=29). The mean change (± standard error) from baseline in endometrial thickness with
BZA 20 mg (–0.23 ± 0.25 mm) and BZA combined (–0.15 ± 0.18 mm) was not
significantly different from that seen with placebo (0.14 ± 0.56 mm) at 7 years. The
number of subjects with endometrial thickness >5 mm at any time interval on therapy
was similar (range, 5.2%-8.3%) among groups. The incidence of endometrial hyperplasia
with BZA was similar to that with placebo. Fewer cases of endometrial carcinoma were
reported with BZA 20 mg (n=0) or BZA combined (n=3) than with placebo (n=7; P <0.01
and P <0.05, respectively; Table). The incidences of ovarian cyst, uterine hemorrhage, and
vaginal hemorrhage were small and similar among the BZA and placebo groups. There
were numerically more cases of histopathologically confirmed ovarian carcinoma in the
BZA 20-mg (n=3) and BZA combined (n=4) groups than in the placebo group (n=0;
Table); the differences were not statistically significant. The incidence of breast carcinoma
in the BZA 20-mg and BZA combined groups was not different from that in the placebo
group (Table). Other breast-related AEs, including breast cysts, fibrocystic breast disease,
and breast pain were reported with similar frequency among groups (Table). Conclusion:
BZA was associated with a neutral effect on the breast and favorable endometrial safety
profile, including fewer cases of endometrial carcinoma compared with placebo, in
postmenopausal women with osteoporosis over 7 years of therapy.
S-8.
Treatment with the Cathepsin K Inhibitor Odanacatib in Postmenopausal
Women with Low BMD: 5 Year Results of a Phase 2 Trial
Andrew Denker1, N. Binkley2, H. Bone3, N. Gilchrist4, B. Langdahl5, H. Resch6, J.
Rodriguez-Portales7, A. Lombardi1, C. Le Bailly De Tilleghem8, C. DaSilva1, E.
Rosenberg1, A. Leung1. 1Merck, Rahway, NJ; 2U. of Wisconsin, Madison, WI; 3Michigan
Bone & Mineral Clinic, Detroit, MI; 4Princess Margaret Hospital, Christchurch, New
Zealand; 5Aarhus U. Hospital, Aarhus, Denmark; 6Medical U. Vienna, Vienna, Austria;
7
Pontificia Universidad Católica de Chile, Santiago, Chile; 8Merck, Brussels, Belgium
Objective: The selective cathepsin K inhibitor odanacatib (ODN) progressively increased
BMD at the spine and hip during a 2-year trial and 2-year extension. Here we report the
results of an additional year. Design: Postmenopausal women of mean age 63 yrs, with
BMD T-scores -2.0 to -3.5 at the lumbar spine or hip, received weekly placebo (PBO) or
ODN 3, 10, 25, or 50mg for 2 yrs in addition to calcium, if needed, and vitamin D3. In
yr 3, women in each treatment group were re-randomized to ODN 50mg or PBO. For yrs
4-5, women receiving PBO or ODN 3mg in yrs 1-2 and PBO in yr 3 were switched to
ODN 50mg; all others continued with their yr 3 treatments. BMD at the lumbar spine
(primary endpoint), femoral neck, trochanter, and 1/3 radius; bone turnover markers; and
safety were assessed. Results: Women entering the yr 4-5 extension receiving PBO
(n=41) or ODN 50 mg (n=100) had similar baseline characteristics. After 5 yrs, in women
who received ODN 50mg continuously from yr 1 (n=13), mean % changes (SE) in BMD
from baseline were: lumbar spine 11.9 (2.1) (Figure), femoral neck 9.8 (1.9), trochanter
10.9 (1.4), total hip 8.5 (1.0), and 1/3 radius -1.0 (1.3). In women who were switched
from ODN 50mg to PBO after 2 yrs (n=14), BMD mean % changes (SE) from baseline
were: lumbar spine -0.4 (1.3) (Figure), femoral neck -1.6 (1.0), trochanter -1.0 (0.8), total
hip -1.8 (0.8), and 1/3 radius -4.7 (1.7). After 5 yrs, in women continuously receiving
ODN 50 mg (n=9-10), geometric mean % changes from baseline (SE) were -67.4 (10.1)
for urine NTX/creatinine, but only -15.3 (5.9) for serum BSAP. In women switched from
ODN 50mg to PBO after 2 yrs (n=10) these changes were 6.0 (7.6) and -11.9 (3.9).
Administration of ODN over 5 yrs compared to PBO was generally well-tolerated.
Conclusion: Women who received ODN 50mg for 5 yrs had a gain in spine and hip BMD
over 5 yrs and showed a sustained reduction in urine NTX/Cr and a smaller reduction in
serum BSAP. As previously reported, discontinuation of ODN results in reversal of BMD
gains.
Table. Incidence of Gynecologic and Breast-related AEs
S-9.
Low Plasma Concentrations of Vitamin D3 are Associated with Increased
Cardiovascular Risk Factors in a Female Nonhuman Primate Model
AE, adverse event; BZA, bazedoxifene.
P <0.01 vs placebo; Fisher exact test.
b
P <0.05 vs placebo; Fisher exact test.
c
Excludes 2 cases that were not confirmed as ovarian carcinoma by
histopathology.
a
34
Matthew J. Jorgensen, PhD1, Peter F. Schnatz, D.O.2,3, Lawrence L. Rudel4, Matthew
Nudy2, Jay R. Kaplan1, Thomas B. Clarkson1. 1Department of Pathology/Comparative
Medicine, Wake Forest School of Medicine, Winston-Salem, NC; 2Department of ObGyn
and Internal Medicine, The Reading Hospital and Medical Center, Reading, PA;
3
Departments of ObGyn & Internal Medicine, Jefferson Medical College of Thomas
Jefferson University, Philadelphia, PA; 4Department of Pathology/Lipid Sciences, Wake
Forest School of Medicine, Winston-Salem, NC
Objective: Recent studies have suggested that most American women have an adequate
dietary intake of vitamin D. Not understood, however, is whether the rather large
individual differences in plasma concentrations of vitamin D3 have any patho-physiologic
significance. The purpose of this study was to investigate whether, and to what extent,
these individual differences in plasma vitamin D concentrations are associated with
important cardiovascular risk factors such as: age, abdominal obesity (waist
circumference), and high-density lipoprotein cholesterol (HDL-C). Design: A cohort of
155 female vervet/African green monkeys (Chlorocebus aethiops sabaeus), ranging in
age from 3-25 years old, were fed a typical Western diet for 7-8 weeks that provided them
NAMS11_Regular-LB_Abstracts-2 8/29/11 4:13 PM Page 4
with a woman’s equivalent of approximately 1,000 IU/day of vitamin D3. Measurements
of vitamin D3 and HDL-C concentrations, as well as waist circumference were obtained.
Results: Among the entire cohort, the range of vitamin D3 concentrations was 19.6 to
142.0 ng/mL (mean ± SE = 66.4 ± 1.7 ng/mL). Plasma vitamin D3 concentrations were
inversely associated with age (r=-0.35, p<0.0001). Among young monkeys (aged: 3-6
years) mean plasma vitamin D3 concentrations were 82.3 ± 3.2 ng/ml versus 58.6 ± 2.9
in older monkeys (aged: 16-25 years). Plasma vitamin D3 concentrations were inversely
associated with waist circumference (r=-0.19, p=0.016). The females in the lowest quartile
of vitamin D3 concentrations had waist circumferences of 34.1 ± 0.7 cm versus the highest
quartile with waist circumferences of 31.7 ± 0.6 cm. Plasma vitamin D3 concentrations
were positively correlated with HDL-C (r= 0.20, p=0.01). Thus, the lowest quartile of
vitamin D3 had mean HDL-C concentrations that were 13.6 mg/dL less than the highest
quartile. Conclusion: Lower plasma concentrations of vitamin D3 were significantly
associated with older age, increased abdominal obesity, and decreased HDL-C. Therefore,
higher plasma concentrations of vitamin D3 were associated with more favorable
cardiovascular risk factors.
S-11.
Correlation of age, ethnicity and body mass index (BMI) with change in
bone mineral density over serial Dual Energy X-Ray Absorptiometry
(DXA) scans among postmenopausal women
Vitamin D3 concentrations by age.
S-10.
The Quantification of Vitamin D Receptors in the Coronary Vasculature
and Association with Atherosclerosis
Peter F. Schnatz, D.O.1,2, Matthew Nudy1, David M. O’Sullivan, PhD1, J. Mark Cline,
DVM, PhD3, Susan E. Appt, DVM3, Xuezhi Jiang, MD1, Jay R. Kaplan3, Thomas B.
Clarkson3. 1ObGyn & Internal Medicine, The Reading Hospital and Medical Center,
Reading, PA; 2ObGyn & Internal Medicine, Jefferson Medical College of Thomas
Jefferson University, Philadelphia, PA; 3Pathology/Comparative Medicine, Wake Forest
University, Winston-Salem, NC
Objective: The activated vitamin D receptor (VDR) may have an important role in
vascular health. The objective of this study was to evaluate whether there is an association
between the abundance of VDR’s in the coronary vasculature and the degree of
atherosclerosis. Design: Utilizing a cohort of 39 postmenopausal female cynomolgus
monkeys with varying stages of atherosclerosis, transverse sections of the left anterior
descending artery (LAD) were analyzed for cross-sectional area, plaque thickness, and
VDR quantity using immunohistochemical H-score analysis. The quantities of VDR’s
were analyzed as a continuous variable and were divided at the median H-score into higher
vs. lower groupings. Results: In the LAD, a significant negative correlation was observed
between the quantity of VDR and plaque size (both cross-sectional area [p<0.001, see
figure] and plaque thickness [p<0.001]). Monkeys in the low vitamin D receptor group had
a significantly greater cross-sectional plaque area (1.2 mm2) and greater plaque thickness
(0.3 mm) than those in the high VDR group (0.4 mm2, p=0.005; 0.1 mm, p=0.003,
respectively). Conclusion: Lower concentrations of VDR’s in a main coronary artery
were associated with greater arterial plaque size in female postmenopausal monkeys.
Given that coronary artery atherosclerosis is a major cause of coronary heart disease in
postmenopausal women, further research to ascertain the relationship between Vitamin D
and atherosclerosis is warranted.
Sobia Khan, M.D., Devorah R. Wieder, MD MPH, Holly Thacker, MD, Benjamin Nutter.
Women’s Health, Cleveland Clinic Foundation, Cleveland, OH
Objective: Identifying the factors that modify bone health helps determine, the population
most at risk for osteoporosis in order to initiate preventive and treatment measures
accordingly. The primary goal of this study was to analyze the correlation of age, ethnicity
and BMI with change in the Bone Mineral Density (BMD) among postmenopausal
women receiving serial DXA scans. BMI has an independent relationship with BMD
regardless of age or ethnicity and it is postulated and concluded in various studies that
obesity may decrease the risk of osteoporosis by increasing BMD. However, the effect of
age and ethnicity in conjunction with BMI on change in bone mineral density over time
has not been as well established. Design: Study Group : This retrospective, comparative
study was conducted on an initial data set containing 9,727 records for 1,956 patients
who underwent Hologic Dual Energy X-Ray Absorptiometry scans at the Cleveland Clinic
from April 2002 through February 2008. For purposes of analysis, records were kept only
if the patient’s initial scan occurred post-menopause (age ≥ 50 years), and when a followup scan occurred within 2 - 5 years of a previous scan. A significant change in BMD is
denoted by an absolute change of more that 0.03 g/cm2. The final data set contained 609
records for 430 patients. Of these patients, 274 had two scans, 133 had 3 scans, and the
remainder had four scans. The median age of patients was 53.1 years, and the study group
was primarily Caucasian. The median time between scans was 26.22 months and the
median time since the initial scan was 32.66 months. Statistical Methods: Mixed Effects
modeling approaches were employed to estimate the relationship between outcome
variables and age, ethnicity, BMI, and time since initial scan while entering the patient as
a random effect. Inspection of the random effects variances showed that these variances
were very small; suggesting that mixed effects techniques could be abandoned without
altering the results. Typical modeling approaches were used for calculation and
interpretation. Linear regression was used to investigate the relationship of the predictors
with raw BMD change while logistic regression was used to investigate the relationship
with the occurrence of a significant change in BMD. Initially, interaction terms were
included in the models, but were removed when they showed to be non-significant factors.
Variance inflation factors (VIF) were calculated to evaluate the presence of
multicollinearity. Analyses are performed using R 2.12.2 statistical software. Modeling is
performed using the functions in the lme4 and rms packages. Statistical significance is
determined by a p-value ≤ 0.05. Results: Age and ethnicity showed no significant effect
on change in BMD. BMI had a relationship with increased BMD where every unit
increase in BMI was associated with a 0.0004 g/cm2 increase in BMD (p = 0.19), however
BMI showed no significant effect on change in BMD over time. Each month elapsing
since the initial scan was associated with a -0.0004 g/cm2 decrease in BMD (p =0.002;
see Table 1.1). Each month elapsing since the initial scan was associated with a 2%
increase in odds of a significant change (p < 0.001; see Table 1.1). Conclusion: While
BMI does bear a relationship with bone mineral density in postmenopausal women, low
BMI was not associated with significantly greater decreases in BMD over time in this
study. Decrease in BMD over time was also not correlated with age or ethnicity. This
study highlights the need for a more complex risk profile to assist in predicting changes
in BMD for an individual patient.
See table on next page.
35
NAMS11_Regular-LB_Abstracts-2 8/29/11 4:13 PM Page 5
Scientific Sessions (continued)
Table 1.1: Linear Model Summary for Serial BMD Loss in the Hip
S-12.
Efficacy of flibanserin as a potential treatment for Hypoactive Sexual
Desire Disorder in North American postmenopausal women
James A. Simon, MD, CCD, NCMP, FACOG1, Leonard DeRogatis3, Lorraine
Dennerstein2, Michael Krychman4, Brad Shumel5, Miguel Garcia5, Vladimir Hanes5,
Michael Sand, PhD, MPH5. 1George Washington University, Washington, DC; 2University
of Melbourne, Melbourne, VIC, Australia; 3Center for Sexual Medicine at Sheppard Pratt,
Baltimore, MD; 4Southern California Center for Sexual Health and Survivorship
Medicine, Newport Beach, CA; 5Boehringer-Ingelheim, Ridgefield, CT
Objective: To assess the efficacy of 24 weeks’ treatment with flibanserin 100mg qhs for
generalized, acquired Hypoactive Sexual Desire Disorder (HSDD) in postmenopausal
women. Design: This was a double blind, randomized, placebo-controlled trial of
flibanserin 100mg qhs in postmenopausal women (n=949). Co-primary endpoints were
change from baseline to study end in: 1) the number of satisfying sexual events (SSE)
and 2) Female Sexual Function Index (FSFI-d) desire domain, both assessed over a 28 day
period. Secondary endpoints included: Female Sexual Distress Scale-Revised (FSDS-R)
total and FSDS-R Item 13 scores (distress associated with low sexual desire))Efficacy
analyses were based on the full analysis set (FAS), which included all women who were
randomized, received one dose of study medication and had at least one on treatment
efficacy assessment. Intent to treat, last observation carried forward (LOCF) analysis was
used for all efficacy analyses. Results: Mean (SD) baseline data were: SSE 2.1 (2.3) and
FSFI-d 1.8 (0.7). The mean changes from baseline to study end in the efficacy endpoints
are given in the table below. Adverse events leading to discontinuation were experienced
by 3.5% of women receiving placebo and 8.1% of women receiving flibanserin 100mg.
Serious adverse events were reported by 0.8% of women receiving placebo and 1.7% of
women receiving flibanserin 100mg. Conclusion: In this North American trial in
postmenopausal women with HSDD, flibanserin 100 mg qhs was associated with
clinically meaningful and statistically significant improvements in both co-primary
endpoints, the number of SSE and sexual desire (FSFI desire domain), and the secondary
endpoints for distress associated with sexual dysfunction (FSDS-R total) and distress
associated with low sexual desire (FSDS-R Item 13) compared with placebo.
3.6 y) participated in this substudy: BZA 20 mg/CE 0.45 mg (n=115), BZA 20 mg/CE
0.625 mg (n=123), BZA 20 mg (n=49), CE 0.45 mg/MPA 1.5 mg (n=56), or PBO
(n=116). At 12 months, the mean change from baseline at Month 12 in scores for sleep
adequacy, sleep disturbance, sleep problems overall (sleep problems index I and II), and
time to fall asleep was significantly improved with BZA 20 mg/CE 0.625 mg compared
with PBO (P <0.05 for all; Table); significant improvement in sleep disturbance and time
to fall asleep scores was seen with BZA 20 mg/CE 0.45 mg compared with PBO (P <0.05
for each). Mean change from baseline at Month 12 in scores for sleep adequacy, sleep
disturbance, overall sleep problems (sleep problems index I and II), and time to fall asleep
was significantly improved with CE 0.45 mg/MPA 1.5 mg compared with PBO (P <0.05
for all). At 12 months, MENQOL results (Table) showed that women treated with
BZA/CE 0.45 or 0.625 mg had significant improvement in total and vasomotor scores
compared with PBO (P <0.05 for each). In addition, the mean change from baseline in
sexual and physical function scores was significantly improved with BZA 20 mg/CE
0.625 mg compared with PBO (P <0.01 for each) at Month 12. Significant improvement
was also seen in the CE 0.625-mg/MPA 1.5-mg group in the mean change from baseline
in total and vasomotor scores compared with the PBO group (P <0.05 for each) at 12
months. Conclusion: Symptomatic postmenopausal women treated with BZA/CE had
significant improvement in sleep parameters and HR-QoL over 1 year. These results are
consistent with those seen in previous SMART trials, and support BZA/CE as an effective
treatment option for menopausal symptoms while protecting the endometrium in
postmenopausal women.
Table. Mean Change From Baseline in MOS Sleep Scale Measures and MENQOL
Scores at 12 Months (SMART-5)
Mean change from baseline to study end in efficacy endpoints
P <0.05 vs placebo.
a
*p=0.004 versus placebo
**p<0.0001 versus placebo
***p=0.0059 versus placebo
****p=0.0083 versus placebo
CONCURRENT SESSION #2
S-13.
Effects of Bazedoxifene/Conjugated Estrogens on Sleep Parameters and
Health-related Quality of Life in Postmenopausal Women
JoAnn V. Pinkerton1, Kaijie Pan2, Lucy Abraham2, Jill Racketa2, Arkadi A. Chines2,
Sebastian Mirkin2. 1University of Virginia Health System, Charlottesville, VA; 2Pfizer Inc,
Collegeville, PA
Objective: Bazedoxifene/conjugated estrogens (BZA/CE) is a tissue selective estrogen
complex (TSEC) that has been shown in previous studies to be an effective treatment for
vasomotor symptoms (VMS) while ensuring endometrial safety in women less than or
more than 5 years from menopause. The effects of BZA/CE on sleep parameters and
health-related quality of life (HR-QoL) were assessed in the Selective estrogens,
Menopause, And Response to Therapy (SMART)-5 trial. Design: In this phase 3, doubleblind, placebo (PBO)-controlled study (N=1,843), postmenopausal women with an intact
uterus were randomized to BZA 20 mg/CE 0.45 or 0.625 mg, BZA 20 mg, CE 0.45
mg/medroxyprogesterone acetate (MPA) 1.5 mg, or PBO daily for 12 months. Sleep and
HR-QoL were evaluated in a subset of women with bothersome VMS and sleep problems
at baseline. The Medical Outcomes Study (MOS) sleep scale was used to evaluate
individual sleep parameters, including sleep adequacy, sleep disturbance, sleep quantity,
somnolence, snoring, shortness of breath or headache, and time to fall asleep; overall
sleep problems were measured with 2 summary index scores (sleep problems index I and
II). The Menopause-Specific Quality of Life (MENQOL) questionnaire was used to
evaluate HR-QoL; the questionnaire comprises 4 domains (vasomotor, psychosocial,
sexual, and physical function) that were scored individually and averaged for a total score.
Results: A total of 459 women (mean age, 53.4 y; mean years since last menstrual period,
36
S-14.
Effect of Escitalopram on Insomnia Symptoms and Subjective Sleep
Quality in Healthy Menopausal Women with Hot Flashes: A Randomized
Controlled Trial in the MsFLASH Network
Kristine Ensrud, MD, MPH1, Joesph Larson2, Katherine Guthrie2, Hadine Joffe, MD,
MSc3, Andrea LaCroix2, Carol Landis4, Katherine Newton5, Susan Reed4, Barbara
Sternfield6, Nancy Woods4, Ellen Freeman7. 1Medicine, University of Minnesota / VA
Medical Center, Minneapolis, MN; 2Fred Hutchinson Cancer Research Center, Seattle,
WA; 3Harvard Medical School, Boston, MA; 4University of Washington, Seattle, WA;
5
Group Health Research Institute, Seattle, WA; 6Research, Kaiser Permanente, Oakland,
CA; 7Medicine, University of Pennsylvania, Philadelphia, PA
Objective: Determine the effect of escitalopram on insomnia symptoms and subjective
sleep quality in healthy menopausal women with hot flashes. Design: Randomized,
double-blind, placebo-controlled, parallel arm, multicenter trial of escitalopram (10-20
mg/day in a flexible-dose regimen) for 8 weeks in 205 women. By design, nearly half of
the study population was African-American. Insomnia symptoms (Insomnia Severity
Index [ISI]) and subjective sleep quality (Pittsburgh Sleep Quality Index [PSQI]), a priori
specified secondary outcomes, were collected at baseline and week 4 and 8. Of 205
women randomized, 200 (98%) provided ISI data and 198 (97%) provided PSQI data at
week 8. Results: At baseline, mean hot flash frequency was 9.78/day (SD 5.60), mean ISI
was 11.4 (SD 6.3), and mean PSQI was 8.0 (SD 3.7). Treatment with escitalopram reduced
ISI at week 8 (mean difference -2.00, 95% CI: -3.43 to -0.57, p <0.001 overall treatment
effect), with mean reductions of -4.73 (95% CI -5.72 to -3.75) in the escitalopram group
and -2.73 (95% CI -3.78 to -1.69) in the placebo group. Reduction in PSQI was greater
in the escitalopram versus placebo group (mean difference at week 8 -1.31, 95% CI -2.14
to -0.49, p <0.001 overall treatment effect). Clinical improvement in insomnia symptoms
and subjective sleep quality (defined as a 50% or greater decreases in ISI and PSQI from
baseline) was observed more frequently in the escitalopram group versus placebo group
(ISI: 50.0% versus 35.4%, p=0.04; PSQI 29.6% versus 19.2%, p=0.09). Conclusion:
Among healthy menopausal women with hot flashes, escitalopram at 10-20 mg/day
compared with placebo reduced insomnia symptoms and improved subjective sleep
quality at 8 weeks of follow-up.
S-15.
Hot Flashes Recur Rapidly After Discontinuation of the SSRI
Escitalopram: Results from the MsFLASH Research Network
Hadine Joffe, MD, MSc1, Katherine A. Guthrie, PhD2, Lee Cohen, MD1, Janet Carpenter,
PhD, RN3, Joseph Larson, MS2, Andrea LaCroix, PhD2, Ellen W. Freeman, PhD4.
1
Psychiatry, Massachusetts General Hospital, Boston, MA; 2Fred Hutchinson Cancer
Research Center, University of Washington School of Public Health, Seattle, WA; 3School
of Nursing, Indiana University, Indianapolis, IN; 4Department of Obstetrics/Gynecology,
University of Pennsylvania, Philadelphia, PA
Objective: Hot flashes are known to recur after hormonal therapy is discontinued. As
non-hormonal medications such as selective serotonin reuptake inhibitors (SSRI’s) are
used more widely to treat hot flashes, it is important to understand whether hot flashes
similarly recur after SSRI discontinuation. In an 8-week randomized controlled trial of
escitalopram, the Menopause Strategies: Finding Lasting Answers for Symptoms and
Health (MsFLASH) Research Network found that escitalopram was more effective than
placebo in treating bothersome hot flashes (p<0.001). In the current analysis, we examine
the prevalence and predictors of hot flashes recurring 3 weeks after escitalopram was
discontinued under double-blinded conditions. We hypothesized that recurrence of hot
flashes would be common and predicted by menopausal and psychological characteristics
at treatment initiation. Design: Caucasian and African-American peri- and
postmenopausal women with 4+ bothersome hot flashes per day were randomized to
escitalopram (10–20mg/day) vs. placebo for 8 weeks. At the end of the trial, there was a
3-week double-blinded discontinuation phase during which time medication was stopped.
Hot flash frequency was measured continuously with a daily diary during the screening,
treatment, and discontinuation phases of the trial. Hot flash recurrence was defined as hot
flash frequency at the end of 3 weeks within 20% of the level reported at baseline. A
subgroup analysis was conducted among those whose hot flashes responded to
escitalopram (≥30% decrease in hot flashes from baseline to week 8). Logistic regression
models were developed to determine which a priori characteristics predicted recurrence
among all randomized to escitalopram and then among those responding to escitalopram.
Demographic and menopausal characteristics and baseline symptom levels of hot flashes,
insomnia [Insomnia Severity Index], depression and anxiety were included in the
multivariable model if they showed a univariate association. Results: Of 104 assigned to
escitalopram, 97 (93%) completed the 8-week trial, and 93 (89%) provided hot flash data
through the end of the discontinuation phase. The mean hot flash frequency was 9.9 (SD
6.2) per day at baseline and 7.2 (SD 6.3) per day at the end of the discontinuation phase.
Hot flashes recurred in 36 (39%) women after treatment discontinuation, and in 20 (29%)
of 68 women who responded to escitalopram. Univariate models showed that Caucasian
race, postmenopausal status, and higher levels of insomnia symptoms at baseline predicted
hot flash recurrence (all p<0.05). In adjusted models, only higher levels of insomnia
symptoms remained a significant predictor of hot flash recurrence (odds ratio [OR], 95%
confidence interval [CI] for a 5-point increase in the ISI: 1.60, 1.04–2.47, p=0.03).
Analyses restricted to the subgroup of women who responded to escitalopram revealed
that Caucasian race, insomnia symptoms, and BMI were associated with hot flash
recurrence in unadjusted models (all p<0.10). However, in adjusted models, only
Caucasian race showed a trend toward an increased likelihood of hot flash recurrence
(OR 4.76, 95% CI 0.88–25.0 p=0.07). Conclusion: Hot flashes recurred rapidly—within
3 weeks after treatment discontinuation—in approximately one-third of women whose
hot flashes were treated with and responded to the SSRI escitalopram. Women with higher
levels of insomnia symptoms at baseline were most likely to report recurrence of hot
flashes. These results provide the first evidence that hot flashes recur rapidly in a
significant proportion of women after short-term treatment with non-hormonal SSRI
therapies.
S-16.
Depression and Anxiety Is Associated with Non-Restorative Sleep in Periand Post-Menopausal Women
Masakazu Terauchi, MD, PhD1, Shiro Hiramitsu, MD1, Mihoko Akiyoshi1, Yoko Owa1,
Kiyoko Kato1, Satoshi Obayashi, MD, PhD1, Eisuke Matsushima2, Toshiro Kubota, MD,
PhD1. 1Department of Obstetrics and Gynecology, Tokyo Medical and Dental University,
Tokyo, Japan; 2Department of Psychosomatics, Tokyo Medical and Dental University,
Tokyo, Japan
Objective: To investigate the association of depression and anxiety with sleep
disturbances in peri- and post-menopausal women. Design: We retrospectively analyzed
the records of 442 peri- and post-menopausal women who were enrolled in the Systematic
Health and Nutrition Education Program, conducted at the Menopause Clinic of the Tokyo
Medical and Dental University Hospital, between May 2005 and December 2010. In this
program, the physical and mental health of these women was assessed using the
Menopausal Health-Related Quality of Life (MHR-QOL) questionnaire developed in our
clinic, and the Hospital Anxiety and Depression Scale (HADS) questionnaire developed
by Zigmond and Snaith. The MHR-QOL questionnaire contains 9 somatic and 12
psychological items including difficulty in initiating sleep (DIS) and non-restorative sleep
(NRS), while the HADS comprises 7 anxiety and 7 depression items. The subjects
responded to each item in the questionnaires on a 4-point Likert scale. The following
issues were addressed by evaluating the MHR-QOL and the HADS scores of these
women: (1) The prevalence of sleep disturbances; (2) the association of somatic and
psychological symptoms with sleep disturbances; and (3) the association of depression
and anxiety with sleep disturbances. Results: (1) The percentage of women who reported
DIS and NRS more than 3 nights per week was 31.9% and 40.7%, respectively. (2) DIS
and NRS severity scores were correlated better with psychological symptom scores
(depressed mood, panic attacks, etc.) than with somatic ones (hot flashes, night sweats,
etc.) in the MHR-QOL questionnaire. (3) DIS and NRS severity scores were correlated
significantly with most of the depression items (HADS-D) and anxiety items (HADS-A)
in the HADS questionnaire, and the absolute values of correlation coefficients were
generally larger in NRS than in DIS. (4) Multiple linear regression analysis was performed
with the NRS severity score as the dependent variable, and the HADS items #2 (“I still
enjoy the things I used to enjoy.”) and #3 (“I got a sort of frightened feeling as if something
awful is about to happen.”) scores as representative predictors for depression and anxiety,
respectively. Standardized partial correlation coefficients for depression and anxiety was
-0.248 (p = 0.009) and -0.243 (p = 0.011). Conclusion: Sleep disturbances are highly
prevalent in peri- and post-menopausal women, and are closely related with psychological
symptoms rather than somatic ones. Depression and anxiety is more strongly associated
with NRS than with DIS, and the both factors equally contribute to make sleep less
restorative in these women.
S-17.
Plasma Melatonin Circadian Rhythms in Menopausal Depressed vs.
Normal Control Women
Barbara L. Parry, M.D., Charles Meliska, PhD, Diane Sorenson, Ana Lopez, Fernando
Martinez, Henry Orff. Psychiatry, University of California, San Diego, La Jolla, CA
Objective: The aim was to test the hypothesis that the amplitude or phase (timing) of
melatonin circadian rhythms differs in menopausal depressed patients (DP) vs. Normal
Control (NC) women because the constellation of endocrine patterns accompanying
menopausal depression remains incompletely characterized. Design: In a university
hospital setting, we measured plasma melatonin every 30 minutes from 18:00-10:00 h in
dim light (< 30 lux) or dark, serum gonadotropins and steroids (18:00, 06:00 h) and mood
(Hamilton and Beck depression ratings) in 29 (18 NC, 11 DP) peri- or post-menopausal
women. Main outcome measures were plasma melatonin (onset, offset, synthesis offset,
duration, peak concentration, area under the curve) and mood. Results: Multi- and
univariate analyses of covariance (MANCOVA, ANCOVA) showed melatonin offset time
was delayed (P = .045) and plasma melatonin was elevated in DP compared with NC (P
= .044) across time intervals. Multiple regression analyses showed that years past
menopause predicted melatonin duration, and that melatonin duration, body mass index
(BMI), years past menopause, Follicle Stimulating Hormone (FSH) level and sleep end
time were significant predictors of baseline Hamilton (P = .0003) and Beck (P = .00004)
depression scores. Conclusion: Increased melatonin secretion that is phase-delayed into
the morning characterized menopausal DP vs. NC. Years past menopause, FSH, sleep end
time and BMI may modulate effects of altered melatonin secretion in menopausal
depression.
S-18.
Cognition in Perimenopause: How menopause transition stage affects the
trajectory of cognitive change over time
Miriam Weber1, Leah Rubin2, Pauline Maki2. 1Department of Neurology, University of
Rochester, Rochester, NY; 2Department of Psychiatry, University of Illinois at Chicago,
Chicago, IL
Objective: Studies of objective cognitive performance during the menopausal transition
reveal small, but measurable, declines in verbal fluency, verbal episodic memory and
processing speed. The aim of this study was to determine the trajectory of cognitive
function in perimenopausal women over one year. Specifically, we aimed to determine if
cognitive function declines from baseline to one year follow-up and if cognitive change
over time differs according to perimenopausal group status at baseline. Design: 59
perimenopausal women between the ages of 40 and 60 were categorized into early
(changes in menstrual flow amount, duration and/or cycle length) (n=9), middle (≥ 1
episode of cycle irregularity, with no skipping of periods) (n=16) or late (≥ 1 skipped
period) (n=34) perimenopause based on self-reported menstrual patterns, according to
criteria from the Seattle Midlife Women’s Health Study. We adminstered a comprehensive
neuropsychological battery and a self-report inventory of depression. Women were
evaluated at baseline, 6 months, and one year follow-up. We had a 97% retention rate
(n=57) from baseline to 6 months and a 96% retention rate (n=55) from 6 months to 1
year. Two women were evaluated at baseline and 1 year, but were not seen at 6 months.
Women who participated in at least two evaluations were included in the current analyses
(n=59). Composite z-scores were computed for the following cognitive domains: working
memory/attention, executive function, visuospatial function, motor funtion, verbal
learning, and verbal memory. All primary hypotheses were tested using mixed effects
regression models, controlling for age, education and self-reported depressive symptoms.
Results: As a group, women’s performance on all cognitive domains significantly
improved from baseline to follow-up (p<.001). However, the trajectory of change over
time differed as a function of baseline perimenopausal group status. Women in early
perimenopause showed no significant improvement in motor and verbal memory
performance over time, and women in middle perimenopause showed no significant
improvement in verbal learning and verbal memory over time. Women in late
perimenopause significantly improved in all cognitive domains. Women in early
perimenopause showed significantly more improvement in verbal learning tasks than
women in middle perimenopause (p<.001) across time. Conclusion: Cognitive function
in perimenopause may not be linear, but instead may change over the course of the entire
menopusal transition. The trajectory of this change may differ as a result of
perimenopausal group status. The cognitive domains of verbal learning, verbal memory
and fine motor speed and dexterity may be particularly vulnerable during perimenopause.
37
Scientific Sessions (continued)
CONCURRENT SESSION #3
S-19.
Adiposity and hot flashes in midlife women: Timing is everything
Rebecca C. Thurston, PhD1,2, Nanette Santoro, MD3, Karen A. Matthews, PhD1,2.
1
Psychiatry, University of Pittsburgh, Pittsburgh, PA; 2Epidemiology, University of
Pittsburgh, Pittsburgh, PA; 3Obstetrics and Gynecology, University of Colorado, Denver,
CO
Objective: It is a long-held belief that adiposity protects women from hot flashes due to
androgen-to-estrogen sex steroid bioconverstion by adipose tissue. However, recent
findings from epidemiologic investigations suggest that greater adiposity is associated
with increased hot flash reporting. This work is largely based upon questionnaire measures
of hot flashes, without the use of real-time self-reporting or physiologic measures of hot
flashes. Dose-response relations between adiposity and flashes have also been unexplored.
The aim of this study was to use diary and physiologic measures of hot flashes to examine
associations between body size/composition and hot flashes. Variations in these relations
by age were also examined. Design: A subcohort of women in the Study of Women’s
Health Across the Nation (N=52; 25 African American, 27 non-Hispanic Caucasian) who
reported hot flashes in the past two weeks, had an intact uterus and both ovaries, and were
not taking medications impacting hot flashes, were recruited in 2008-2009. Women
completed anthropometric measures (bioimpedence analysis of total percentage of body
fat, body mass index (BMI), waist circumference), and a blood draw (estradiol (E2),
SHBG, FSH). Women also underwent four days of ambulatory sternal skin conductance
monitoring with a diary, such that physiologic and self-reported hot flashes were both
recorded simultaneously. Associations between anthropometrics and hot flashes were
estimated with generalized estimating equations, adjusting for factors associated with hot
flashes (age, race, anxiety). Interactions by age were examined in all models. The
influence of menopausal stage was not examined as 90% of the sample was
postmenopausal. Results: Higher BMI (odds ratio (OR), 95% confidence interval
(CI)=0.97(0.94-0.99), p<0.05) and waist circumference (OR(95%CI)=0.98(0.97-0.99),
p<0.01) were associated with fewer physiologic hot flashes. Interactions by age (p’s<0.05)
indicated that the inverse associations of body fat, BMI, and waist circumference with
hot flashes were most apparent among the oldest women in the sample. Additionally
controlling for E2 and SHBG reduced, but did not eliminate, age-related variations in
relations between body size/composition and hot flashes. Conclusion: Higher adiposity
was associated with fewer physiologic hot flashes among older women with hot flashes,
suggesting that as ovarian estrogen production ceases, the role of peripheral adiposity as
a source of estrogen becomes more important in predicting hot flashes. A modifying role
of age should be considered in understanding the role of adiposity in hot flashes. SWAN
has support from the NIH, DHHS, through NIA, NINR and NIH ORWH (NR004061;
AG012505, AG012535, AG012531, AG012539, AG012546, AG012553, AG012554,
AG012495). This work was also supported by AG029216. The content of this abstract is
solely the responsibility of the authors and does not necessarily represent the views of
the NIA, NINR, ORWH or NIH.
S-20.
Cardiovascular, Cerebrovascular and Hepatic Safety of Desvenlafaxine
Over 1 Year in Women With Vasomotor Symptoms Associated With
Menopause
David F. Archer1, JoAnn V. Pinkerton2, Christine J. Guico-Pabia, MD, MBA, MPH3,
Eunhee Hwang3, Ru-fong J. Cheng3. 1Eastern Virginia Medical School, Clinical Research
Center, Norfolk, VA; 2University of Virginia Health System, Charlottesville, VA; 3Pfizer
Inc, Collegeville, PA
Objective: Clinical data have shown that the serotonin-norepinephrine reuptake inhibitor
desvenlafaxine (administered as desvenlafaxine succinate) is effective for the treatment
of moderate to severe vasomotor symptoms (VMS) associated with menopause. However,
one 12-month study noted cardiovascular events in 5/612 women taking desvenlafaxine.1
The objective of the current study was to examine the safety of desvenlafaxine including
estimated incidence of cardiovascular events, cerebrovascular events, and hepatic events
for desvenlafaxine vs placebo in symptomatic, generally healthy menopausal women
seeking treatment for VMS. Design: This was a multicenter, randomized, double-blind,
placebo-controlled safety and efficacy study in postmenopausal women seeking treatment
for symptomatic VMS. Following a 1 week titration period, desvenlafaxine 100 mg/d was
administered for up to 1 year. Safety was monitored with physical examinations, adverse
events (AEs) collection, vital sign measurements, laboratory evaluations, and
electrocardiogram results. Potential cases of ischemic cardiovascular events (coronary
heart disease-related death, new onset myocardial infarction [MI], or unstable angina
requiring hospitalization, and unscheduled revascularization procedures) and
cerebrovascular events (definite stroke or probable stroke) identified by investigator
reports and periodic adverse event review based on Standardized Queries of the Medical
Dictionary for Regulatory Activities were reviewed by blinded adjudication boards.
Hepatic events (liver function tests [alanine aminotransferase or aspartate
aminotransferase] >5X upper limit of normal) were identified based on central laboratory
data. Results: A total of 2118 participants took ≥1 dose of study medication (mean
therapy duration of 280 days); 1066 received desvenlafaxine and 1052 received placebo.
There was 1 event adjudicated to be a cardiovascular event: 1 placebo-treated participant
had an MI. One desvenlafaxine-treated participant was adjudicated to have a probable
stroke. Two participants in each treatment group had hepatic events. The excess risk of
desvenlafaxine compared with placebo per 1000 woman-years for cardiovascular events
was -1.07 (90% CI -2.86, 0.72), for cerebrovascular events 1.11 (90% CI -0.68, 2.9), and
38
for hepatic events 0.08 (90% CI -3.51, 3.67). Conclusion: There was no evidence of
increased risk of cardiovascular, cerebrovascular, or hepatic events for desvenlafaxine vs
placebo in this study, indicating that desvenlafaxine was safe for use in women with VMS.
S-21.
Pulse Wave Velocity is Positively Correlated with Atherosclerosis Extent
in Midlife Female Nonhuman Primates
Susan E. Appt, DVM1, Kylie Kavanagh, DVM1, Haiying Chen1, Jay R. Kaplan1, Jason
Lazar2, Thomas B. Clarkson1. 1Comparative Medicine, Wake Forest School of Medicine,
Winston Salem, NC; 2Division of Cardiovascular Medicine, State University of New York
Downstate Medical Center, Brooklyn, NY
Objective: To determine whether, in midlife females, a non invasive measure of arterial
stiffness (pulse wave velocity, PWV) is a marker of atherosclerosis extent, and to
investigate the relationships among PWV and plasma cardio-metabolic risk markers.
Design: Subjects were 49 socially housed, female cynomolgus monkeys (Macaca
fascicularis) with an estimated mean age of 19 years (~57 women’s equivalent years).
After consuming a human-like diet containing animal protein and cholesterol for ~two
years, PWV, cardio-metabolic risk markers, and Left common iliac artery atherosclerosis
(LCI, via surgical biopsy) were measured. The iliac artery has been validated as a
surrogate for coronary artery atherosclerosis extent in the cynomologus monkey. Pulse
waveforms were recorded using tonometry (SphygmoCor®) at the brachial and femoral
arteries sequentially. Transit time was calculated using the R wave of a simultaneously
electrocardiography recording and the difference in distance between the brachial artery
site and the supra sternal notch, and the distance between the supra sternal notch and the
femoral artery site. Multivariate regression analysis was used and data are reported as
correlations (r) and mean (±SE). Results: PWV for female monkeys was similar to that
observed in adult human subjects (7.7±0.28, range = 4.4 – 12 meters/second). Significant
associations were observed between PWV and both LCI atherosclerosis extent (r = 0.33,
p=0.02) and systolic blood pressure (r = 0.33, p=0.02). There was a tendency for positive
associations with plasma LDL + VLDL (r = 0.29, p=0.06), BMI (r = 0.27, p=0.06, kg/m2),
HgA1c% (r = 0.22, p = 0.12) and plasma glucose (r = 0.20, p = 0.14). In addition, a
multivariate analysis indicated that plasma glucose was an independent predictor of PWV
(p<0.04). No significant associations were observed with diastolic blood pressure or other
lipid variables. Conclusion: The results of this study suggest that, like women, arterial
stiffness is a significant predictor of atherosclerosis in nonhuman primates. Further studies
are indicated to determine whether measures of insulin resistance are similarly correlated
with PWV, as has been reported in postmenopausal women.
S-22.
Tissue Selective Estrogen Receptor α Agonists Reverse Weight Gain
without Causing Mammary Gland or Uterine Proliferation
Mary Tagliaferri, MD1, Elise Saunier, PhD1, Omar I. Vivar2, Andrea Rubenstein1,
Sreenivasan Paruthiyil1, Scott Baggett1, Richard E. Staub1, Isaac Cohen1, Dale C.
Leitman2,1. 1Bionovo, Emeryville, CA; 2Department of Nutritional Science and
Toxicology, University of California Berkeley, Berkeley, CA
Objective: Long-term estrogen deficiency increases the risk of obesity, diabetes and
metabolic syndrome in postmenopausal women. Menopausal hormone therapy containing
estrogens might prevent these conditions, but its prolonged use increases the risks of
breast cancer, strokes and thromboembolic events. Animal studies indicate that the
beneficial effects of estrogens in adipose tissue and adverse effects in the mammary gland
and uterus are mediated by estrogen receptor alpha (ERα). One strategy to prevent obesity,
diabetes and metabolic syndrome is to improve the safety of estrogens by developing
tissue selective ERα drugs that act as agonists in adipose tissue, but not in the mammary
gland and uterus. To date, tissue selective ERα agonists have not been identified. Design:
We considered plant extracts as a source of tissue selective ERα agonists and screened
multiple extracts using transfection assays. Numerous plant extracts were screened for
ERα activity by transfecting U2OS cells with the classic estrogen responsive element
(ERE) upstream a minimal thymidine kinase promoter linked to the luciferase reporter
gene (ERE tk-Luc) and an expression vector for human ERα. Based on these findings we
selected two plant extracts that we used in a high fat diet fed mouse model to examine if
they reverse weight gain and fat accumulation. Potential adverse proliferative effects of
the plant extracts in the mammary gland and uterus were assessed in a mouse model where
treatment time was 49 days. Last, to examine the tissue specific effects of the plant extracts
at the genomic level, we compared gene expression profiles in gonadal fat, mammary
gland and uterus in response to estradiol and the extracts. Results: Extracts from two
plants, Radix Glycyrrhiza uralensis (RG) and Radix Pueraria lobata (RP) selectively
activated multiple ERα responsive reporters, and reversed weight gain and fat
accumulation comparable to estradiol in ovariectomized obese mice maintained on high
fat diet. Unlike estradiol, RG and RP did not induce proliferative effects on the mammary
gland and uterus. Gene expression profiling demonstrated that RG and RP induced
estrogen-like regulation of genes in abdominal fat, but not in the mammary gland and
uterus. RG and RP also behaved differently than the SERMs, raloxifene and tamoxifen,
because they did not antagonize the effects of estradiol. Conclusion: The compounds in
extracts from RG and RP might constitute the first class of tissue selective ERα agonists
to prevent and/or reverse weight gain, fat accumulation, metabolic syndrome and other
conditions in postmenopausal women.
S-23.
Cortical Thickness Analysis in Depressed,
Perimenopausal and Postmenopausal Women
Medication-free,
Luciano Minuzzi, MD, Ph.D, Benicio N. Frey, Geoffrey B. Hall, Ivan Skelin, Stefanie
Attard, Meir Steiner, Claudio N. Soares, MD, PhD, FRCPC. Department of Psychiatry and
Behavioural Neurosciences, McMaster University, Hamilton, ON, Canada
Objective: The menopausal transition and early postmenopausal years have been
described as a period of higher risk for the development of depressive symptoms or Major
Depressive Disorders (MDD) in a woman’s life. Previous structural imaging studies
conducted in patients with MDD have shown volume reductions in several brain regions
that are involved in emotional regulation. However, the impact of MDD on cerebral grey
matter in midlife women has yet to be determined. In a recent functional magnetic
resonance imaging (fMRI) study, we demonstrated that depressed perimenopausal women
failed to deactivate the rostral anterior cingulate cortex (ACC) during a response inhibition
task. The objective of the present study is to measure grey matter cortical thickness in the
brain of medication-free midlife women with diagnosis of MDD in comparison to healthy
controls by using structural MRI. Furthermore, we aim to investigate at regional level
whether grey matter abnormalities in the ACC correlate with depressive symptoms in this
population. Design: Thirteen medication-free peri/postmenopausal women (mean age =
49.5 ± 3.8 years) diagnosed with a major depressive episode (mean total MADRS
scores=19.2 ± 5.0, mean duration of depressive episode=17.6 months) and 13 healthy
(non-depressed), age-matched controls (mean age=50.1 ± 5.3 years, mean total MADRS
scores=2.6 ± 1.7) underwent high-resolution structural MRI in a 3T scanner. The images
were pre-processed in order to segment the brain into grey, white and CSF tissue classes
and to align cortical structures across the subjects. Grey matter cortical thickness was
measured using the Laplace method. Volume-of-interests (VOIs) corresponding to ACC
subregions (dorsal, rostral, and subgenual) were manually drawn on the three dimensional
image. Voxel-wise statistical analysis was performed between the groups using
BrainVoyager QX software. Results: Voxel-wise analysis revealed decreases in grey
matter thickness in subjects with MDD in the temporal lobe (superior and middle temporal
gyri), angular gyrus, superior frontal gyrus, ACC, anterior midcingulate cortex and
precuneus. Depressed subjects presented thicker grey matter in the right dorsolateral
prefrontal cortex (DLPFC). Moreover, VOI analysis in the ACC showed decreases in
cortical thickness in the left hemisphere of depressed subjects (ANOVA, F=6.4, p=0.01).
Lastly, left dorsal ACC presented higher cortical thinning in subjects with MDD (< 20%,
p=0.02). Depressive symptoms (i.e., MADRS scores) were inversely correlated with
cortical thickness in the left ACC (p=0.01). No effect of age on cortical thickness was
found in subjects with MDD or controls. Conclusion: To our knowledge, this is the first
study examining cortical thickness in medication-free MDD midlife women with
depression. Depressed, unmedicated midlife women showed reduction in cortical
thickness in a number of brain regions, and an increase in cortical thickness in the right
DLPFC compared to healthy age-matched controls. In addition, severity of depressive
symptoms was associated with cortical thinning in the left ACC. These results suggest that
the untreated depressive disorder in perimenopausal and early postmenopausal women
might have a negative impact in discrete brain regions associated with mood and cognitive
control. Future studies should clarify the potential effects of pharmacologic treatments on
cortical brain structure in this population.
S-24.
Circadian Rhythm of Hot Flashes in Symptomatic Postmenopausal
Women and Men Undergoing GnRH Analog Therapy
Lauren L. Drogos, M.A.1, Rhoda Jamadar2, Leah Rubin2, Stacie Geller3, Lee Shulman4,5,
Suzanne Banuvar4, David Walega, M.D.5, Pauline M. Maki1,2. 1Psychology, University of
Illinois at Chicago, Chicago, IL; 2Psychiatry, University of Illinois at Chicago, Chicago,
IL; 3Obstetrics and Gynecology, University of Illinois at Chicago, Chicago, IL;
4
Northwestern University, Chicago, IL; 5Northwestern Memorial Hospital, Chicago, IL
Objective: Hot flashes (HFs) are the most commonly reported and bothersome
menopausal symptom, but can also occur in up to 80% of men undergoing androgen
deprivation therapy (ADT) for prostate cancer. Hot flashes have been associated with
memory changes, loss of bone density, cardiovascular disease and depressive symptoms
in women across the menopausal transition. Previous reports have shown a circadian
rhythm of hot flashes in healthy postmenopausal women, but not breast cancer survivors.
The current study compared and contrasted circadian rhythm of hot flashes in
symptomatic postmenopausal women and men undergoing ADT. Design: Forty-one
subjects provided data, including 14 men (Mean age = 69.7) from a study investigating
HF and cognition in men undergoing GnRH analog therapy for prostate cancer and 54
women (Mean age = 52.7) from a baseline visit for two clinical trials investigating efficacy
of non-hormonal hot flash treatments. Subjects wore an ambulatory sternal skin
conductance monitor (Biolog Model 3991x/2-HFI) for 24 hours. Objective (i.e., > 1.8 or
> 2.0 micromho increase in 45 seconds or 30 seconds for men and women, respectively)
HF were recorded, with specific cut-offs chosen based on prior validation studies. To
reduce inter-individual variability in the time of hot flashes for subjects on different
sleep/wake schedules, data were normalized to each subjects’ wake time. Data were
collated in 30-minute bins, and a repeated measure ANOVA with polynomial contrasts
were used to test for changes in hot flash frequency during the recording period. Curve
estimate regression was used to determine the presence of a circadian rhythm in frequency
of hot flashes across a 24-hour recording period. Results: Women averaged 17 objective
HFs (13.2 daytime, 3.7 nighttime) and men averaged 12.4 HFs (8.9 daytime, 3.5
nighttime) over a 24-hour period. Both men and women showed a circadian rhythm of
HFs evidenced by a significant quadratic contrast (p<.001). No sex differences were
observed in the circadian pattern or the frequency of HFs. Hot flash frequency peaked
over the late afternoon through early evening with a nadir at nighttime. Conclusion: To
our knowledge, this is the first study directly comparing objective hot flashes in women
and men undergoing ADT therapy. The finding that the circadian rhythm was similar
between the sexes, suggests that similar mechanisms might contribute to HF in both
women and men on ADT. Given previous findings of altered circadian rhythms of hot
flashes in breast cancer survivors, our data suggests that HFs in men undergoing ADT
may be more similar to HFs in healthy women than HFs in breast cancer survivors.
Understanding overlap in the physiology and circadian rhythm of HFs across patient
populations might suggest which patient populations might benefit from HF treatments.
CONCURRENT SESSION #4
S-25.
Measurement of Urogenital Symptoms
Lila E. Nachtigall, MD, NCMP1, Gloria A. Bachmann, MD2. 1Department of Obstetrics
& Gynecology, New York University Langone Medical Center, New York, NY;
2
Department of Obstetrics, Gynecology and Reproductive Sciences, UMDNJ-Robert
Wood Johnson Medical School, New Brunswick, NJ
Symptoms of vulvo-vaginal dryness, irritation, itching, and discharge, dyspareunia, dysuria
and frequent urinary tract infections are associated with the hypoestrogenic state, most
notable in menopausal women, regardless of etiology. The SWAN study confirmed clinical
observations that vaginal dryness, especially as it relates to dyspareunia, can be a symptom
during the perimenopausal transition as well. The largest cohort of menopausal women
studied that reports on the prevalence of self-reported urogenital symptoms is derived from
the data of 98,705 postmenopausal women enrolled in the observational study and clinical
trials of the Women’s Health Initiative. These data indicate that as many as one quarter of
menopausal women will report urogenital symptoms (vaginal or genital dryness, 27.0%;
vaginal or genital irritation or itching, 18.6%; vaginal or genital discharge, 11.1%; and
dysuria, 5.2%). In addition to vaginal estrogen therapy, other interventions, including oral
Dt56a a phtoestrogen, and vaginal DHEA are being researched to reverse symptoms and
signs of urogenital atrophy. To measure the response of a studied intervention, a subjective
measurement of severity is often accomplished by patient self report-using a likert scale
grading, which also is applicable in clinical practice. Although attempts have been made
to document and objectively measure severity of atrophic urogenital changes observed by
pelvic examination, none to date have been validated. Also, there are no biomarkers that
can be followed for treatment response. For estrogen therapy, efficacy is also measured by
the objective endpoints of pH and maturation index. Quantitative measurement of increased
vaginal secretions as an efficacy measure for both estrogen and non-estrogen interventions
using calcium alginate nasopharyngeal swabs or nylon-flocked cervicovaginal swabs have
been studied to date only in non-human animal studies.
MsFLASH RESEARCH NETWORK
S-26.
New Clinically Relevant Findings from the MsFLASH Research Network:
The Escitalopram Trial
Andrea Z. LaCroix1, Ellen W. Freeman2, Kristine Ensrud, MD, MPH3, Susan D. Reed,
MD, MPH4. 1Public Health Sciences Division, Fred Hutchinson Cancer Research Center,
Seattle, WA; 2Departments of Obstetrics/Gynecology and Psychiatry, University of
Pennsylvania Medical School, Philadelphia, PA; 3VA Medical Center, University of
Minnesota, Minneapolis, MN; 4School of Nursing, Indiana University, Indianapolis, IN
The Menopause Strategies: Finding Lasting Answers for Symptoms and Health
(MsFLASH) clinical trials network, supported by the National Institute on Aging as a
cooperative agreement, is conducting a series of randomized clinical trials designed to test
new interventions for menopausal symptoms. Our first randomized trial of escitalopram in
healthy menopausal women with hot flashes, found that treatment significantly reduced the
frequency, severity and bother of vasomotor symptoms during 8 weeks of treatment.
Delving further into the effects of escitalopram on vasomotor symptoms, we then examined
the efficacy of escitalopram compared with placebo for: (1) daytime and nighttime hot
flash frequency, severity and bother; (2) number of flash free days and nights; and (3) hot
flash interference (the Hot Flash Related Daily Interference Scale). Escitalopram
significantly reduced both daytime (18%; p=0.001) and nighttime (15%; p=0.003) hot
flashes compared to placebo. The escitalopram group experienced about one-half more
flash-free day (p=0.03) and one-half more flash-free night (p=0.001) compared to the
placebo group. Hot flash interference scores were reduced by 18.1 points in the
escitalopram group compared to 14.6 points in the placebo group over the course of the trial
(p=0.01). Despite these encouraging findings, concerns about the use of SSRIs for hot
flashes include potential side effects, especially related to insomnia and sexual function.
Further evaluation of the effect of escitalopram versus placebo on insomnia symptoms
(Insomnia Severity Index) and subjective sleep quality (Pittsburgh Sleep Quality Index)
revealed that escitalopram at 10-20 mg/day compared with placebo reduced insomnia
symptoms and improved subjective sleep quality at 4 and 8 weeks of follow-up (p≤0.001
for overall treatment effect for both sleep measures). Escitalopram did not significantly
impact the overall Female Sexual Function Index, or a single item from the Female Sexual
Distress Scale, although escitalopram decreased lubrication relative to placebo (-0.6 points
difference on a 6-point scale; p=0.02) in sexually active women. We conclude that
escitalopram provides relief for vasomotor symptoms, does not increase symptoms of
insomnia and does not affect overall sexual function in non-depressed women with
bothersome hot flashes. Future MsFLASH trials will test several other therapies for relief
39
Basic Science Poster Presentations
of menopause symptoms including yoga, aerobic exercise, Omega-3 fatty acid
supplementation, low dose estrogen and venlafaxine using designs that allow for side-byside comparison of treatment effects relative to placebo and/or comparison groups.
of menopause
symptoms
including
yoga, aerobic
exercise, Omega-3 fatty acid
BASIC
SCIENCE
POSTER
PRESENTATIONS
supplementation, low dose estrogen and venlafaxine using designs that allow for side-byside comparison of treatment effects relative to placebo and/or comparison groups.
P-1.
Comparative analysis of estrogenic receptor subtype selectivity of 17βSCIENCE
PRESENTATIONS
estradiol,BASIC
its metabolites,
and POSTER
related compounds
using highly accurate
reporter gene based assay
1
Jan
Chow1, Sylvia Fong1, Isaac Cohen1, Dale Leitman2. 1Bionovo
P-1.Bohuslav, PhD , Sylvia
of Nutritional
Science,
University
of California,
Inc.,
Emeryville,analysis
CA; 2Department
Comparative
of estrogenic
receptor
subtype
selectivity
of 17βBerkeley, CA
estradiol,
its
metabolites,
and
related
compounds
using
highly
accurate
Objective: Estrogen metabolites are known to circulate in the female body and produce
reporter gene
based
assay
biological
responses.
After
the discovery of a second estrogen receptor (ERβ) it is
1
1
2 1
Jan Bohuslav,
PhD1, Sylvia
Chow1,ligands
Sylvia Fong
, Isaac
Cohen
, Daleand
Leitman
. Bionovo
important
to distinguish
if estrogen
produce
similar
activities
pharmacological
of Nutritional
University
of differences
California,
Inc.,
Emeryville,
CA;in2Department
outcomes.
Selectivity
the transactivation
for each Science,
ER subtype
may reveal
Berkeley,
CA
in bio-pharmacological
activities and provide insights into the physiological actions of
Objective:
Estrogen
metabolites
knowntimes
to circulate
in the female
body
selective estrogen
metabolites
atare
different
in a woman’s
life, as
welland
as produce
provide
biological
After thedevelopment
discovery ofofanew
second
estrogen
receptor (ERβ)
it is
informationresponses.
for pharmaceutical
estrogens
for menopausal
hormone
importantDesign:
to distinguish
if estrogen
ligandssensitive
produce similar
activities and
pharmacological
therapy.
We developed
a highly
and reproducible
reporter
gene celloutcomes.
in the transactivation
for each
ER subtype
may reveal
differences
based
assaySelectivity
for the measurement
of ERα- and
ERβ-specific
estrogenic
activities.
This
in
bio-pharmacological
activities
and provide
insightsresponsive
into the physiological
actions
of
assay
is based on transient
expression
of estrogen
element (ERE)
based
selective
estrogen
metabolites
at different
times
in a ERα
woman’s
life, in
ashuman
well ascell
provide
reporter gene
together
with estrogen
receptors
(either
or ERβ)
lines
information
for pharmaceutical
of new of
estrogens
forallows
menopausal
hormone
that
do not contain
endogenous development
ER. Low variability
the assay
us to determine
therapy. Design:
We developed
a highly
sensitive
gene cellconcentration
of estrogens
in unknown
samples
with and
errorreproducible
less than 20%reporter
at sub-nanomolar
based assay
for the
measurement
ERα- and
ERβ-specific
estrogenic
This
range.
Results:
In this
report, weofcompare
activities
of several
naturalactivities.
and synthetic
assay is based
on transient 17α-estradiol,
expression of estrogen
element (ERE) based
estrogens
(17β-estradiol,
estrone, responsive
estriol, 2-hydroxyestradiol,
4reporter gene together
with estrogen receptors
(either ERα in
or four
ERβ)different
in human
cell lines
hydroxyestradiol,
2-methoxyestradiol,
and ethinylestradiol)
mammalian
that
do not
contain
ER.and
Low
variability
the assay
allowspotencies
us to determine
cell lines
(HEK
293,endogenous
U2OS, MCF7,
ECC-1).
The of
relative
estrogenic
(REP)
concentration
of estrogens
unknownassamples
with
error less
thanof20%
at sub-nanomolar
of tested compounds
were in
calculated
the ratios
between
EC50
17β-estradiol
and the
range.
Results:
In this (REP>1
report, we
compare activities
of several
and synthetic
individual
compounds
corresponds
to a potency
highernatural
than 17β-estradiol).
estrogens
estrone, and
estriol,
4Estriol
had (17β-estradiol,
the highest ERβ 17α-estradiol,
specific REP (REP=34)
a low2-hydroxyestradiol,
ERα REP (REP=0.05)
hydroxyestradiol,
2-methoxyestradiol,
andERβ-dependent
ethinylestradiol)
in four
differentas
mammalian
indicating
its strong
preference to activate
gene
transcription
compared
cell17α-estradiol.
lines (HEK 293,
U2OS, MCF7,
and ECC-1).
relative
estrogenic
(REP)
to
In contrast,
ethinylestradiol
hadThe
higher
preference
for potencies
the activation
of
of tested
compounds
werevs.calculated
as the
ratios Based
betweenonEC50
of 17β-estradiol
and the
the
ERα
(ERα
REP = 5.1
ERβ REP
= 0.15).
the ERα
specific REP,
individual compounds
(REP>1
corresponds >>
to a17β-estradiol
potency higher
than 17β-estradiol).
compounds
can be ranked
as ethinylestradiol
>estrone,
estriol > 17αEstriol had
the highest ERβ >specific
REP (REP=34)
and a low ERα REP
(REP=0.05)
estradiol,
2-hydroxyestradiol
4-hydroxyestradiol,
2-methoxyestradiol.
The ERβ
specific
indicating
strong preference
to activateethinylestradiol
ERβ-dependent gene
transcription
as compared
ranking isits estriol
>17β-estradiol>
>estrone
>17α-estradiol,
2to
17α-estradiol. In
contrast, ethinylestradiol
had higher preference
for the activation
of
hydroxyestradiol,
4-hydroxyestradiol,
and 2-methoxyestradiol.
Conclusion:
Our findings
ERα
(ERα REP
= 5.1
vs.abundant
ERβ REP
= 0.15).
Based17β-estradiol,
on the ERα estrone
specificand
REP,
the
demonstrate
that the
most
human
estrogens,
estriol
compounds
can
be ranked
as ethinylestradiol
>> ERβ,
17β-estradiol
estriol >ERα17αhave different
relative
potencies
towards ERα and
and may >estrone,
therefore produce
estradiol,
2-hydroxyestradiol
Themenopause.
ERβ specific
and ERβ-specific
responses >as4-hydroxyestradiol,
their levels change2-methoxyestradiol.
during pregnancy or
A
ranking
is estriol >17β-estradiol>
ethinylestradiol
>estrone
>17α-estradiol,
2greater understanding
of how the differences
in the structures
of metabolites
leads to ER
hydroxyestradiol,
4-hydroxyestradiol,
and 2-methoxyestradiol.
findings
subtype transcriptional
specifity could lead
to the development ofConclusion:
new classesOur
of estrogens
demonstrate
that the most
abundant human estrogens, 17β-estradiol, estrone and estriol
to prevent menopausal
symptoms.
have different relative potencies towards ERα and ERβ, and may therefore produce ERαand ERβ-specific responses as their levels change during pregnancy or menopause. A
P-2. understanding of how the differences in the structures of metabolites leads to ER
greater
subtype
transcriptional
specifity could
lead to the
development
new radicals
classes of estrogens
The ability
of Cyclosporine
(CsA)
induce
oxigenoffree
in a rat
to
prevent menopausal
osteoblast
cell line symptoms.
Hoon Choi1, Heung Yeol Kim2. 1Sanggye Paik Hospital, Inje University, Seoul, Republic
of Korea; 2Kosin University, Busan, Republic of Korea
P-2.
Objective: This study examined the ability of Cyclosporine (CsA) to induce apoptosis in
The
ability of Cyclosporine (CsA) to induce oxigen free radicals in a rat
a rat osteoblast cell line. Design: Rat osteoblast ROS 17/2.8 cells were cultured, and
osteoblast
cell 0.1-40
line μg/mL CsA for 24 hours after plating of cells. Cell viability was
treated with1 with
1
Hoon
Choi ,by
Heung
Yeol assay.
Kim2. Western
SanggyeBlot
PaikAnalysis
Hospital,
Inje
University,
Seoul,antibodies
Republic
determined
the
MTT
was
done
with primary
Busan, Republic
of Korea(ROS) synthesis was measured by
of caspase-3
Korea; 2Kosin
to
and University,
caspase-8. Reactive
oxygen species
Objective:
This study
examined
the abilitydecreased
of Cyclosporine
(CsA) to inducemanner
apoptosis
in
flowcytometry.
Results:
Cell viability
in dose-dependent
with
aincreasing
rat osteoblast
cell line. Design:
Rat osteoblast
ROS
17/2.8
cells
were
concentrations
of CsA. Treatment
of ROS
17/2.8
cells
with
0.1,cultured,
0.5, 1, 5, and
10,
treated
with
with 0.1-40CsA
μg/mL
CsA for
24 80%,
hours after
of cells.
Celland
viability
20, or 40
μg/mLg/mL
caused
85%,
73%,plating
60%, 45%,
40%,
27% was
cell
determined
by the MTTWestern
assay. Western
Blot Analysis
was donecaspase-3
with primary
antibodies
viability,
respectively.
blot analysis
showed reduced
expression
and
to
caspase-3
and
caspase-8.
Reactive
oxygen
species
(ROS)
synthesis
was
measured
induced caspase-8. The ROS in a dose-and time-dependent manner were increased by
by
flowcytometry.
Results:
Cell
viability
decreased
in
dose-dependent
manner
with
CsA. Conclusion: These results suggest that CsA can induce oxygen free radicals which
increasing
concentrations
of
CsA.
Treatment
of
ROS
17/2.8
cells
with
0.1,
0.5,
1,
5,
10,
appears to trigger apoptosis by activating pro-apoptotic signals. CsA plays a role in the
20, ortransplatation
40 μg/mLg/mL
caused
80%, 73%,
60%, 45%,
40%, and 27% cell
postboneCsA
diseases
via85%,
the induction
of apoptosis
in osteoblast.
viability, respectively. Western blot analysis showed reduced caspase-3 expression and
induced caspase-8. The ROS in a dose-and time-dependent manner were increased by
P-3. Conclusion: These results suggest that CsA can induce oxygen free radicals which
CsA.
appears to trigger Responses
apoptosis by activating
signals.
CsA plays a Women:
role in the
Psychological
to Acutepro-apoptotic
Exercise in
Middle-Aged
post- transplatation
bone diseases
via the induction
of apoptosis
in osteoblast.
Contrasting
the Effects
of Vigorous
and Moderate
Intensity
Steriani Elavsky, Ph.D.1, Okan Micoogullari, M.Sc.2. 1Department of Kinesiology, Penn
2
State
P-3. University, University Park, PA; Physical Education and Sports Department, Middle
East Technical University, Ankara, Turkey
Psychological Responses to Acute Exercise in Middle-Aged Women:
Objective: In spite of the multiple health benefits of physical activity, only 47% of
Contrasting
the Effects
of Vigorous
Moderate
Intensity
middle-aged
women
report meeting
current and
physical
activity (PA)
guidelines and nearly
2 1
Steriani
Elavsky,
Ph.D.1, Okanphysical
Micoogullari,
M.Sc.
. Department
of Kinesiology,
27%
report
no leisure-time
activity
at
all
(BRFSS,
2007).
ObjectivePenn
PA
2
Physical
Education
and
Sports
Department,
Middle
State
University,
University
Park,
PA;
surveillance data paint even bleaker picture with less than 3% of females
accumulating
East
Technical
University,
Ankara,
Turkey
sufficient PA levels (Troiano et al., 2008). Additionally, substantial drop-out rates (50%)
Objective:
spite ofactivity
the multiple
health
benefits
of physical
activity,
only with
47%the
of
plague mostIn
physical
programs.
These
statistics
seem to be
in conflict
middle-aged
womennotion
reportthat
meeting
current
physical
guidelines
and nearly
generally accepted
physical
activity
makesactivity
people(PA)
feel good.
One hypothesis
27%
report
no leisure-time
physical
activity
at all
(BRFSS,
2007).
Objective
PA
put forth
to explain
this contradiction
regards
exercise
intensity,
whereby
more
pleasurable
surveillance data paint even bleaker picture with less than 3% of females accumulating
sufficient PA levels (Troiano et al., 2008). Additionally, substantial drop-out rates (50%)
plague most physical activity programs. These statistics seem to be in conflict with the
generally accepted notion that physical activity makes people feel good. One hypothesis
put forth to explain this contradiction regards exercise intensity, whereby more pleasurable
40
responses from exercise are expected to ensue from moderate intensity exercise rather
than vigorous exercise. The main study objectives were (1) to evaluate psychological
(affect, anxiety, self-efficacy) responses to vigorous and moderate intensity exercise in
midlife women; (2) to assess whether responses varied by menopausal, vasomotor
symptom, weight, and fitness status; and (3) to assess whether affective responses to
responseswere
fromassociated
exercise are
expected
ensue frommeasured)
moderate physical
intensity activity
exercise levels.
rather
exercise
with
overall to
(objectively
than vigorous
exercise. The main
study
objectives
were (1)
to evaluate
psychological
Design:
Community-dwelling
midlife
women
of varying
menopausal
status
(age range
(affect,years;
anxiety,
self-efficacy)
to vigorous
andwere
moderate
intensity
in
40-60
M=51.4,
SD=4.2),responses
not on hormone
therapy
recruited
for a exercise
daily diary
midlifeofwomen;
(2) to
whether outcomes.
responses As
varied
vasomotor
study
PA effects
on assess
psychological
partbyof menopausal,
the study, 134
women
symptom, weight,
andintensity
fitness status;
(3)(maximal
to assessgraded
whether
affective
to
completed
a vigorous
exerciseand
bout
exercise
test)responses
and 121 of
exercise
were associated
overall
(objectively
activitypace
levels.
them
completed
a moderatewith
intensity
exercise
bout onmeasured)
a treadmillphysical
at self-selected
but
Design:
Community-dwelling
midliferesponses
women ofwere
varying
menopausal
of
moderate
intensity. Psychological
assessed
before, status
during,(age
andrange
after
40-60bout
years;
SD=4.2),
not onpost
hormone
therapy
recruited
for a bout.
daily Heart
diary
each
andM=51.4,
also 20 and
40 minutes
exercise
for thewere
moderate
intensity
studyperceived
of PA effects
on psychological
outcomes.
As part
of the tostudy,
134 exercise
women
rate,
exertion,
and oxygen uptake
were also
monitored
quantify
completedOverall
a vigorous
intensity
exercise
bout assessed
(maximalobjectively
graded exercise
test)
and 121 of
intensity.
physical
activity
levels were
through
accelerometry
them completed
a moderate intensity
exerciseRepeated
bout on ameasures
treadmillANOVA
at self-selected
pace but
across
a 2-week monitoring
period. Results:
and MANOVA
of moderate
intensity.
Psychological
responses
were assessed
before,
during, and
after
were
conducted
separately
for pre and
post exercise
responses
and responses
during
each bout Overall,
and also 20
andwere
40 minutes
post exercise
for the
moderate
intensitytobout.
Heart
exercise.
there
more general
and more
positive
responses
moderate
rate, perceived
exertion,
andsignificant
oxygen uptake
were alsoinmonitored
to quantify
exercise
intensity
exercise,
including
enhancements
positive affect
(d=.47, p<.001),
intensity.of
Overall
levels
were assessed
objectively
through
accelerometry
feelings
energyphysical
(d=.52,activity
p<.001),
psychological
wellbeing
(d=.62,
p<.001),
and selfacross a 2-week
period. Results:
Repeated
measures
ANOVA
and MANOVA
efficacy
(d=.36, monitoring
p<.001). Responses
to certain
mood states
(anxiety
and tension)
varied
were conducted
separately
for pre and
post with
exercise
responses
and responseswomen
during
significantly
by fitness
and symptom
status,
higher
fit and asymptomatic
exercise. Overall,
there
were more
andmagnitude
more positive
responses
to moderate
experiencing
anxiety
reducing
effectsgeneral
of larger
as compared
to lower
fit and
intensity exercise,
including
significant
enhancements
in positive
affect (d=.47,
p<.001),
symptomatic
women.
Responses
were
more varied
for vigorous
exercise,
with
feelings of energyand
(d=.52,
p<.001),women
psychological
(d=.62, p<.001),
andmood
selfoverweight/obese
symptomatic
generallywellbeing
showing significantly
smaller
efficacy (d=.36,
Responses
certain
mood states
(anxiety
and tension)
varied
enhancing
effectsp<.001).
than normal
weighttoand
asymptomatic
women
(examples
presented
in
significantly
by fitness and symptom
with higher
fit and asymptomatic
women
Figure
1). Overweight/obese
womenstatus,
also showed
significantly
larger decreases
in
experiencing
anxietyvigorous
reducingexercise..
effects ofMore
largeractive
magnitude
compared
to lower
and
calmness
following
womenaschose
to exercise
at fit
higher
symptomatic
women.
Responses
were more
varied
for responses
vigorous during
exercise,
with
intensities
during
the moderate
self-paced
bout but
affective
exercise
overweight/obese
and symptomatic
women generally
showing
significantlyFrom
smaller
mood
were
largely unrelated
to overall physical
activity levels.
Conclusion:
a moodenhancing effects
than normal
weightindicate
and asymptomatic
women
(examples
presented
in
enhancing
perspective,
these results
that moderate
intensity
exercise
should be
Figure 1).for
Overweight/obese
women also showed
significantly
larger decreases
promoted
midlife women. Deconditioned,
overweight
or obese women
are likely in
to
calmnesstofollowing
vigorousless
exercise..
More
activethe
women
chose
exercise atwomen
higher
respond
vigorous exercise
positively,
creating
potential
for to
discouraging
intensities
during
moderateregular
self-paced
boutactivity.
but affective
during
exercise
from
pursuing
and the
maintaining
physical
From aresponses
motivational
perspective,
were largely
to overall physical
levels.forms
Conclusion:
From
a moodwomen
shouldunrelated
be also encouraged
to engageactivity
in enjoyable
of physical
activity
that
enhancing
perspective,
these results indicate that moderate intensity exercise should be
are
personally
meaningful.
promoted for midlife women. Deconditioned, overweight or obese women are likely to
respond to vigorous exercise less positively, creating the potential for discouraging women
P-4. pursuing and maintaining regular physical activity. From a motivational perspective,
from
women
should beskin
also conductance
encouraged to engage
in enjoyable
forms
of physical activity
that
Two sternal
monitors
for the
measurement
of hot
are
personally
meaningful.and evaluation
flashes:
Comparison
William Fisher, MA, Aimee Johnson, Gary Elkins, Ph.D.. Psychology & Neuroscience,
Baylor
P-4. University, Waco, TX
Objective: Hot flashes, the most common and debilitating symptom of the climacteric,
Two
sternal skin conductance monitors for the measurement of hot
are studied utilizing subjective and objective measures. The ‘gold-standard’ objective
flashes:
andmeasurement
evaluation of hot flashes via sternal skin conductance
measure isComparison
the physiological
William
& Neuroscience,
recordingFisher,
(SSC).MA,
ThisAimee
study Johnson,
comparesGary
two Elkins,
devicesPh.D..
for thisPsychology
measurement,
the Biolog®
Baylor
University,
TX by UFI and an experimental hot flash recorder from Bahr™
Hot Flash
Monitor,Waco,
produced
Objective:
Hot
flashes,
the
most
common
and
debilitating
symptom
of
the
climacteric,
Management, Inc. Though these two devices both measure sternal skin conductance,
they
are
studied
utilizing
and Hot
objective
The ‘gold-standard’
objective
do so
at different
rates.subjective
The Biolog®
Flash measures.
Monitor records
sternal skin conductance
measure
is
the
physiological
measurement
of
hot
flashes
via
sternal
skin
conductance
continuously every second for 24 hours at a time, whereas the Bahr™ Monitor records
recording
This study
compares
for this
measurement,
Biolog®
sternal skin(SSC).
conductance
samping
once two
everydevices
10s. Both
device
are attachedthe
sternally
by
Hot
Flash
Monitor, EEG
produced
by UFIplaced
and aninexperimental
flash recorder
Bahr™
means
of standard
electrodes
a proprietaryhot
electrode
gel andfrom
adhesive
to
Management,
Inc.
Though
these
two
devices
both
measure
sternal
skin
conductance,
they
the skin. Design: In a study of 145 post-menopausal women experiencing severe (50+
do
so
at
different
rates.
The
Biolog®
Hot
Flash
Monitor
records
sternal
skin
conductance
week) hot flashes, participants were asked to wear both of these devices at three different
continuously
second for 24
at NIH-granted
a time, whereas
theofBahr™
Monitor
records
points during every
their participation
in hours
a larger
study
a mind-body
treatment
sternal
skin conductance
once every
10s. Both
device
are attached
sternally
by
for hot flashes.
Hot flashessamping
were assessed
subjectively
and
objectively
using the
Biolog®
means
of standard
EEG
electrodes
placed from
in a proprietary
gel and adhesive
to
and Bahr™
monitor.
Data
were collected
participantselectrode
and comparison
of the data
the
Design:
In awere
study
of 145
post-menopausal
women
experiencing
severe
(50+
fromskin.
the two
devices
made.
Results:
Clear differences
were
visible in the
recorded
week)
flashes,
participants
were the
asked
to wear
both ofdata
theseshowing
devices at
three
different
tracks hot
from
the two
devices, with
Bahr™
monitor
less
erratic
skin
points
during presentaiton,
their participation
in a larger
NIH-granted
study of
treatment
conductance
however,
as this
device recorded
at aa mind-body
tenth the rate
of the
for
hot
flashes.
Hot
flashes
were
assessed
subjectively
and
objectively
using
the
Biolog®
Biolog®, the clarity of the data must be viewed with caution as the comparison of the data
and
monitor. Data
wereevents
collected
from participants
and comparison
of thepaste
data
was Bahr™
not standardized.
Adverse
associated
with toleration
of the electrode
from
two devices
made.
Results:with
Clear
visible
in the recorded
was athe
limitation
of thewere
Bahr™
monitors,
14differences
participantswere
(9.65%)
reporting
adverse
tracks
the two
with (3.45%)
the Bahr™
monitor
data showing
lessthe
erratic
skin
events,from
compared
to 5devices,
participants
reporting
adverse
events from
Biolog®.
conductance
however,with
as this
recorded
at a tenth
the the
rateBahr™
of the
Both monitorspresentaiton,
showed challenges
floordevice
and ceiling
effects.
To date,
Biolog®,
theno
clarity
of the
data must
bethus
viewed
with interpretation
caution as the of
comparison
of be
thedone
data
monitor has
scoring
algorithm,
and
the only
the data can
was
not standardized.
associated
withortoleration
the electrode
paste
by exporting
the data toAdverse
alternateevents
analytical
programs
by visual of
clinical
interpretation.
was
a limitation
of the Bahr™
with 14 participants
(9.65%)
reporting
adverse
In contrast,
the Biolog®
monitormonitors,
utilizes FlashTrax©,
a proprietary
software
that analyzes
events,
to 5 participants
reporting adverse
eventsbaseline
from the
Biolog®.
the datacompared
for an change
in change in(3.45%)
skin conductance
activity from
levels.
This
Both
monitors
challenges
floor
and ceiling
effects.
Bahr™
software
utilizesshowed
a default
setting ofwith
2 μmho
change
/ 30 s to
equateTo
andate,
event.the
Further,
it
monitor
has
no
scoring
algorithm,
and
thus
the
only
interpretation
of
the
data
can
be
done
records button-press subjective markers of hot flash events and flags events as either true
by
exporting
the
data
to
alternate
analytical
programs
or
by
visual
clinical
interpretation.
positive or false negative based on the HF event matching temporally with button-press.
In
contrast,
Biolog® has
monitor
FlashTrax©,
a proprietary
software thathot
analyzes
Though
thisthe
algorithm
beenutilizes
criticized
in the literature
as over-reporting
flash
the
datathe
forabsence
an change
in change
in skin for
conductance
from
levels.
This
events,
of such
an algorithm
the Bahr™activity
monitor
is abaseline
limitation.
Head-tosoftware
utilizes
a
default
setting
of
2
μmho
change
/
30
s
to
equate
an
event.
Further,
it
head comparisons were made between the two devices on participants who wore both
records
subjective
hot flash
events on
anda flags
as either
devices button-press
simultaneously
and alsomarkers
reportedoftheir
hot flashes
diary.events
Clinical
scoringtrue
of
positive
or false
based onthe
theBiolog®
HF eventsoftware-derived
matching temporally
with button-press.
the Bahr™
was negative
utilized against
data comparing
results
Though
algorithm
been criticized
in thehot
literature
over-reporting
hotsample
flash
from eachthis
device
againsthas
participant
self-reported
flashes.as
Conclusion:
In our
events,
the
absence
of
such
an
algorithm
for
the
Bahr™
monitor
is
a
limitation.
Head-toof 145 post-menopausal women who experienced a minimum of 50 hot flashes per week,
head
comparisons
wereMonitor
made between
the two
devices
on participant
participantsself-report
who woreofboth
the Biolog®
Hot Flash
results more
closely
match
hot
devices
simultaneously
and also reported their hot flashes on a diary. Clinical scoring of
flashes over
a 24-hour recording.
the Bahr™ was utilized against the Biolog® software-derived data comparing results
from each device against participant self-reported hot flashes. Conclusion: In our sample
of 145 post-menopausal women who experienced a minimum of 50 hot flashes per week,
the Biolog® Hot Flash Monitor results more closely match participant self-report of hot
flashes over a 24-hour recording.
P-5.
Ambient Temperature and Hot Flashes: Does the weather influence hot
flashes in postmenopausal women?
William Fisher, MA, Kathy Amador, Aimee Johnson, Gary Elkins, Ph.D.. Psychology &
Neuroscience, Baylor University, Waco, TX
Objective: The relationship of ambient temperature and its role in influencing the number
and severity of hot flashes is not yet well-understood. Research into this relationship has
been mixed and to date the influence of menopausal stage on this relationship has been
largely overlooked. In this study, the relationship of ambient temperature to the number
of hot flashes in symptomatic post-menopausal women was investigated. Design: This
study consists of 143 post-menopausal women who were recruited as part of a larger NIHgranted study of a non-pharmacological hot-flash treatment. Baseline assessments of hot
flash diaries as well as physiological measurement of sternal skin conductance were taken.
The baseline assessments were collected over a span of three years to investigate whether
or not ambient temperature during the participant’s 24-hour baseline assessment
influenced the frequency or severity of hot flashes. Results: . Results of this study failed
to show a difference between cold-weather or hot-weather groups in the objective
measures of hot flashes or diary report of hot flashes. There was, however, a significant
correlation between membership to the cold-weather group and in perceived impact of hot
flashes as evidenced by scores from the Hot Flash Related Daily Interference Scale (r= .582, p<.05). Membership to the hot-weather group did not show a significant relationship.
Conclusion: It may be, as the apparently incongruous results of this study may indicate,
that in the population of post-menopausal women, ambient temperature’s role in the
genesis of hot flashes is spurious.
P-6.
Effect of Klimaktoplan on the proliferation of breast cancer cells: in vitro
study
Tak Kim, MD, Ph.D1, Byoung Ick Lee2, Ki hoon Ahn1. 1Dept of obgyn, Korea University
Anam Hospital, Seoul, Republic of Korea; 2Dept of obgyn, Inha University, Incheon,
Republic of Korea
Objective: This study was aimed to investigate the effect of Klimaktoplan on the
proliferation of breast cancer (MCF-7) and normal mammary epithelial cells (MCF-10A).
Design: MCF-7 and MCF-10A cells were cultured in 312.5, 625, and 1250 ug/ml
Klimaktoplan for experimental group. Beta-estradiol and medroxyprogesterone 17-acetate
were used for comparison with Klimaktoplan. Beta-estradiol only (0.001, 0.01, and 0.1
uM), and the combination of estradiol and progesterone (0.001, 0.01, and 0.1 uM betaestradiol; 0.01, 0.1, and 1 μM medroxyprogesterone 17-acetate) were treated. Control
cells for Klimaktoplan and beta-estradiol groups were treated by DMSO, and DMSO and
EtOH for combination group. The proliferation and shape of cells were evaluated by MTT
assay after incubation of 4 days. The effect of lactose, an ingredient in Klimaktoplan were
also assessed by treating 1250 ug/ml lactose. Results: Klimaktoplan of 625 and 1250
ug/ml had a concentration-dependent anti-proliferative effect on breast cancer cells,
although there were no differences of cell proliferation between 312.5 ug/ml Klimaktoplan
and DMSO. Klimaktoplan had no effect on the proliferation of normal mammary cells in
any concentrations. Beta-estradiol and lactose increased the proliferation of breast cancer
and normal mammary cells. The effect of combination of estradiol and progesterone on
the proliferation of breast cancer and normal mammary cells were lower than estradiol
only, but higher than control. Conclusion: Klimaktoplan had an anti-proliferative effect
for breast cancer cells, but not for normal mammary epithelial cells unlike the effects of
estradiol only and the combination of estradiol and progesterone
P-7.
Study on microRNA and its target gene expression using in vitro murine
ovarian follicular growth and aging model
Seung-Yup Ku, MD,PhD1,2, Yong Jin Kim2, Yoon Young Kim2, Sun Kyung Oh2, Seok
Hyun Kim1,2, Young Min Choi1,2, Jung Gu Kim1, Shin Yong Moon1,2. 1Obstetrics and
Gynecology, Seoul National University College of Medicine, Seoul, Republic of Korea;
2
Institute of Reproductive Medicine and Population, Medical Research Center, Seoul
National University, Seoul, Republic of Korea
Objective: Cyclic ovarian follicular growth is a key mechanism of estradiol production
in premenopausal period, and in vitro ovarian follicular growth and aging could be an
important research model to understand the ovarian aging and menopause. MicroRNA is
known to play important roles in development and maturation of eukaryotic cell. This
study is to investigate the changes of microRNA and target gene expression using in vitro
murine ovarian follicular growth and aging model. Design: Preantral follicles were
isolated from ovaries of 2-week-old C57BL6 mouse and cultured in 20 μL-drop of culture
media with supplementation of gonadotropin. After full-growth of follicle, oocyte
maturation and ovulation were induced with supplementation of hCG. Using TRIzol, total
RNA was extracted from granulosa cells of follicle at pre-, and post-hCG. MicroRNA
and its candidate target gene (OCT4, BMP15 and GDF9) were measured with real-time
PCR. Results: Maturation rate of oocyte was 45.2% after hCG supplementation.
Granulosa cells of post-hCG expressed lower let-7b, higher miR-30a and similar let-7c,
miR-16, miR-27a, miR-126, compared to those of pre-hCG. The expression of BMP15
and GDF9 were similar in pre- and post hCG. OCT4 was less expressed in post-hCG.
Conclusion: During in vitro growth and aging of mouse ovarian follicle, profiles of
microRNA and its target gene in granulosa cell may change with follicle maturation.
P-8.
Factors affecting level of preparedness for menopause among
premenopausal women in Leo community, Ido Local Government Area,
Oyo State, Nigeria
Felicia O. Ojo, MPH in view, Oyedunni Arulogun, PhD. Health Promotion and Education,
University of Ibadan, Oyo State, Ibadan, Nigeria
Objective: 1. Assess the level of knowledge of respondents about menopause. 2.
Determine the perception of respondents about menopause. 3. Identify factors affecting
the level of knowledge and perception of respondents about menopause 4. Discover the
level of preparedness of the respondents for menopause. 5. Identify factors affecting the
level of preparedness for menopause among respondents. Design: The survey involved the
use of a three-stage random sampling technique in selecting 426 female respondents
across six streets in Leo community. Six Focus Group Discussions (FGDs) were
conducted. A validated semi-structured questionnaire with a 33-point knowledge scale
was used for collecting quantitative data and five questions were used to assess
participants’ level of preparedness. Analysis of the quantitative data was done using
descriptive, Chi-square and ANOVA statistics while the tape-recorded and transcribed
FGD data were subjected to content analysis. Results: The mean age of the respondents
was 36.6 ± 4.5years and 86.9% were married. Nine percent of the participants had no
formal education while 40.6% had secondary education. Majority (89.0%) of the
respondents were Yoruba and 76.0% had ever heard about menopause. Their sources of
information included, mother (20.0%), health care provider (18.1%), radio (13.4%),
friends (12.0%), sister (5.4%), aunt (5.2%) and internet (2.1%). Respondents’ mean
knowledge score on menopause was 11.6 ± 2.5 while the mean knowledge score by level
of preparedness include: not prepared (5.7 ± 2.1), slightly prepared (10.6 ± 2.9) and very
prepared (18.5 ± 2.5) with a significant difference (p<0.05). Most respondents (97.0%)
were of the opinion that menopause brings relief associated with menstruation to women
while 62.4% perceived that menopause reduces physical strength in women. Only 45.8%
of the respondents stated that they were prepared for menopause and of this 97 (49.5%)
viewed themselves as very prepared. Over half (52.8%) of the respondents between the
age of 40-45 years and 28.5% between the age of 30-39 years perceived themselves as
prepared for menopause (p<0.05). Level of education was not significantly associated
with level of preparedness for menopause. A large proportion of the FGD participants
expressed concerns about the health challenges related to menopause. A few of them were
of the opinion that menstrual stoppage is a disadvantage to women who are yet to give
birth as menopause marks the end of conception. Conclusion: Low level of knowledge
about menopause is a key factor that is affecting the level of preparedness for menopause
among premenopausal women. Public enlightenment and community-based education
on menopause are needed to address these challenges especially among young adult
women.
P-9.
Time is critical for beneficial effects of hormone replacement therapy on
working memory above other cognitive functions
Sophie A. Pettit, Psychology. The Department of Psychology, The University of Plymouth,
Plymouth, United Kingdom
Objective: Oestrogen decline during the menopause leads to decline in cognitive
performance because oestrogen receptor sites are found in the pre-frontal cortex,
hippocampus, hypothalamus and cerebellum of the female brain, areas associated with
memory and attention functions. Extensive research over the past two decades has tested
the effects of administering HRT to maintain oestrogen levels (Sherwin, 2005). MRI
studies with humans have shown improvements in hippocampal volume and frontal
functions with HRT, but these changes were not associated with improved performance
on memory tasks. Similar Benefits of HRT on WM and learning have been found in
human studies, with an initial focus on verbal long-term memory (Sherwin, 1988). Some
studies have found benefits of HRT for working memory (WM), the ability to temporarily
store and manipulate information simultaneously (Duff & Hampson, 2001) but overall
the findings are mixed results (Maki & Zonderman, 2001) and some studies have even
found detrimental effects of HRT (Grigorova & Sherwin, 2006). Typically, previous
studies did not control for time of HRT administration until a general pattern was
established; that those with administrated with HRT at the peri menopausal stage or mixed
samples have found cognitive benefits of HRT whereas those where HRT was
administrated post menopause have not. This pattern is consistent with the critical period
hypothesis (Khoo, 2010); that HRT will only have a positive effect on cognition if the
therapy is initiated during the peri menopause. As well as time of administration of the
therapy, inconsistency in the empirical findings may be due to inconsistency in the type
of cognitive function being assessed. Recent research suggests that frontally-mediated
working memory functions may be particularly sensitive to effects of oestrogen (Low,
Mille, 2002; Shaywitz et al 2010). Design: The present study, therefore, tested the effect
of time of HRT administration on WM function and sustained attention in a naturalistic
sample of 121 women who varied in the time they had begun taking HRT, and a sample
of age-matched controls. Participants were allocated into one of four groups. This included
those who begun HRT during their peri menopause, those who begun HRT during their
post menopause, those who had never taken HRT and were peri menopausal and those
who had never taken HRT and were post menopausal. Mood was measured as a potential
covariate and subjective memory function was assessed with items from the Menopausal
Quality of Life Scale. Participants completed a verbal WM task, a second verbal WM
task with mathematical components, a spatial WM task and a sustained attention task.
Results: A MANCOVA showed a significant difference between task score for both the
verbal WM task (p < .001); the verbal WM task with mathematical components (p < .05)
but not the spatial WM task (p = .096). On closer look it was identified that HRT users
post menopausal scored significantly lower than HRT users peri menopause for the verbal
41
NAMS11_Regular-LB_Abstracts-2 8/29/11 4:13 PM Page 11
Basic Science Poster Presentations (continued)
WM task (p < .001), verbal WM task with mathematical components (p < .005) and the
spatial WM task (p < .05). For the verbal WM task; HRT users post menopause also scored
significantly lower than non-users post menopause, suggesting that HRT taken post
menopause could have detrimental effects on WM score. No significant differences were
identified in the sustained attention task yet post menopausal HRT users made the most
mistakes overall. Conclusion: To conclude, it is suggested that HRT can be beneficial to
WM, especially that with verbal components. However, this may be dependant on time
of initiation of the therapy. For optimal results, the therapy should be administrated as
close to the onset of the menopause as possible. It is also suggested that HRT taken at the
post menopausal stage may have detrimental effects on WM. The exact stage at which this
effect may occur has not yet been defined and should be considered when prescribing
HRT.
P-10.
Vitamin D Receptor Quantity and Plasma Concentration of Vitamin D:
Their Association with Atherosclerosis
Peter F. Schnatz, D.O.1,2, Matthew Nudy1, David M. O’Sullivan, PhD1, J. Mark Cline,
DVM, PhD3, Susan E. Appt, DVM3, Xuezhi Jiang, MD1, Jay R. Kaplan3, Thomas B.
Clarkson3. 1ObGyn & Internal Medicine, The Reading Hospital and Medical Center,
Reading, PA; 2ObGyn & Internal Medicine, Jefferson Medical College of Thomas
Jefferson University, Philadelphia, PA; 3Pathology/Comparative Medicine, Wake Forest
University, Winston-Salem, NC
Objective: The objective of this study was to analyze coronary artery vitamin D receptor
(VDR) abundance, plasma concentration of vitamin D3, and their relationship with
coronary artery atherosclerosis [CAA]. Design: Premenopausal cynomolgus monkeys
(n=39) were fed atherogenic diets containing a woman’s equivalent of both 1,000 IU/day
vitamin D3 and 1,200 mg/day of calcium, and derived their protein from either caseinlactalbumin (C/L, n= 20) or soy protein isolate (soy, n=19). After 36 months consuming
the diets, each monkey underwent surgical menopause (oophorectomy). At that time the
entire group of monkeys was re-randomized to one of the two diets. The consequence
was that half of the monkeys consumed the same diet and half different diets throughout
both the pre- and postmenopausal phase. After 24 post-menopausal months, CAA was
measured in the left circumflex artery (LCX) and left anterior descending artery (LAD).
VDR abundance was determined for the LAD and plasma 25-OH vitamin D
concentrations were assessed. Results: Both the cross-sectional area (mm2) and plaque
thickness (mm) in the LCX as well as the LAD were analyzed in these monkeys. Those
with higher plasma vitamin D concentrations and higher VDR were compared with those
with higher plasma vitamin D concentrations and lower VDR. Smaller plaque sizes were
noted with higher plasma vitamin D concentrations and higher VDR [figure]. For the
LCX, there was also a significantly lower plaque size (both cross-sectional area [figure]
and plaque thickness) in those with higher VDR and lower plasma vitamin D3
concentrations versus those with lower quantities of VDR and higher plasma
concentrations of vitamin D3, p=0.009 and p=0.040, respectively. Conclusion:
Cynomolgus monkeys with higher quantities of VDR have significantly less
atherosclerosis than those with lower quantities of VDR and higher plasma vitamin D3
concentrations. The reason there is an increased plasma vitamin D3 concentration with a
decrease in VDR in association with CAA, and which came first, is not known. If these
findings translate to humans, it might explain why some individuals with higher plasma
concentrations of vitamin D3 have more CAA.
P-11.
An Inverse Relationship between Plasma Vitamin D Concentrations and
C-Reactive Protein Provides a Potential Mechanism For Cardioprotection
Peter F. Schnatz, D.O.1,2, Sharon Vila-Wright, M.D.1, Xuezhi Jiang, MD1, Thomas C.
Register, PhD3, Susan E. Appt, DVM3, Jay R. Kaplan3, Thomas B. Clarkson3. 1ObGyn &
Internal Medicine, The Reading Hospital and Medical Center, Reading, PA; 2ObGyn &
Internal Medicine, Jefferson Medical College of Thomas Jefferson University,
Philadelphia, PA; 3Pathology/Comparative Medicine, Wake Forest University, WinstonSalem, NC
Objective: The inflammatory marker C-reactive protein (CRP) has been positively
associated with coronary heart disease (CHD). The purpose of the present study was to
evaluate potential relationships between this inflammatory biomarker and plasma vitamin
D concentrations in monkeys consuming atherogenic diets which contained either soy
protein isolate or casein-lactalbumin (C/L) as the primary protein source. Design:
Throughout the study, adult female cynomolgus monkeys (n=74) were administered
atherogenic diets with a women’s equivalent of both 1,000 IU/day of vitamin D3 and
1,200 mg/day of calcium. After 36 months of consuming the soy (n=35) or C/L (n=39)
based diets, monkeys underwent oophorectomy to induce surgical menopause and each
diet group was then re-randomized to receive soy (n=36) or C/L (n=38). After 24 postmenopausal months, serum inflammatory markers and 25OH vitamin D concentrations
were assessed. Results: The pre and post-menopausal dietary protein sources had no
effect on post-menopausal concentrations of vitamin D (p=0.63). In all monkeys, there
was a statistically significant inverse relationship between vitamin D concentrations and
CRP at necropsy (r=-0.35, p=0.0026), see figure 1. A significant inverse correlation
between vitamin D concentration and the change in CRP, from premenopause to
postmenopause, was also observed (r=-0.32, p=0.0071). The significant associations
identified between plasma concentration of vitamin D and CRP remained after controlling
for postmenopausal diet. Conclusion: Plasma concentrations of vitamin D were inversely
associated with plasma CRP. The association was strong and independent of menopausal
dietary changes. These findings support the hypothesis that circulating vitamin D
concentrations are associated with anti-inflammatory properties and offer a potential
mechanism by which vitamin D could provide cardio-protection.
P-12.
Comparison of Common Menopause-related Comorbidities and
Procedures among Women with and without Diagnosed Menopause
Symptoms
Nathan Kleinman, PhD1, Nicholas J. Rohrbacker, MS1, Andrew G. Bushmakin2, Jennifer
Whiteley2, Wendy D. Lynch1, Sonali N. Shah, MBA, MS, RPh2. 1HCMS Group,
Cheyenne, WY; 2Pfizer, Inc., New York, NY
Objective: To evaluate the prevalence of osteoporosis, insomnia, depression, anxiety, and
specific procedures within a cohort of employed women over age 40 with diagnosed
menopause symptoms compared with a matched cohort without menopause symptom
diagnoses based on their health insurance claims data. Design: The Human Capital
Management Services database of health care, work absence, and payroll data from large
employers in various industries throughout the US was used. There were 17,322
employees age 40+ with diagnoses (ICD-9-CM codes 627.xx) in their medical claims
data for “menopausal and postmenopausal disorders” (“DX” cohort). The date of first
diagnosis was defined as the index date. A group of women from the database without
menopause symptom diagnoses (“NoDX” cohort) was matched (1 to 1) to the DX cohort,
equating index dates and matching on age, employer, length of medical plan enrollment,
and enrollment end date. By 5-year age bands, the post-index enrollment period
prevalence of osteoporosis (ICD-9-CM 733.0x), insomnia (307.41, 307.42, 307.49,
327.0x, 780.52), major depression (296.2x-296.3x, 311.xx), other depression (298.0x,
300.4x, 309.0x-309.1x), and anxiety (293.84, 300.0x-300.3x, 309.21) diagnoses was
compared between cohorts after the index date. Similarly, the percent of each cohort with
chiropractic, acupuncture, and hysterectomy procedures and the number of chiropractic
procedures per person were compared. Results: Condition and procedure prevalence
values and number of chiropractic services were significantly higher in the DX cohort
than in the NoDX cohort in some of the younger age bands from 40 years to 64 years
(Table). As age increased, the differences between cohorts diminished. Those over 65 had
42
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similar prevalences between the cohorts. The prevalence of osteoporosis increased with
age in both cohorts and was significantly higher in the DX cohort than in the NoDX cohort
up to the 60-64 age range. For major depression and insomnia, the diagnosed group had
significantly higher prevalence up to age 55-59. Other depression prevalence and anxiety
prevalence were significantly higher in the DX cohort up to age 50-54. Prevalence of
chiropractic care was significantly higher in the DX cohort up to age 55-59, and the
average number of chiropractic procedures was higher in the DX cohort up to age 50-54.
Conclusion: Employed women seeking treatment for menopause symptoms were
associated with a higher prevalence of related conditions and procedures and higher
employee costs than similar women without menopause symptom diagnoses. These
results highlighting incremental comorbidity, health care utilization, and costs will be
important for employers sponsoring health care and will aid clinicians in the complex
care of these individuals.
Post-Index Condition and Procedure Prevalence between Menopause Symptom Diagnosis
(DX) and No Menopause Symptom Diagnosis (NoDX) Cohorts
P-14.
Effects of metoclopramide-induced hyperprolactinemia on the
hyaluronan acid of murine endometrium after hormonal replacement
Gabriela C. Cristofani Maioral, MSc1, Regina C. Teixeira Gomes, PhD2, Carina Verna,
Dr1, Roberta B. Wolff, MSc2, Ricardo S. Simões, MSc3, Edmund C. Baracat, PhD3, Helena
B. Nader, PhD4, José M. Soares Júnior, PhD1. 1Department of Morphology, Federal
University of São Paulo, São Paulo, Brazil; 2Department of Morphology and Genetics, São
Paulo Federal University, São Paulo, Brazil; 3Department of Gynecology and Obstetrics,
University of São Paulo Medical School of Medicine, São Paulo, Brazil; 4Department of
Biochemistry, São Paulo Federal University, São Paulo, Brazil
Objective: To evaluate the effects of metoclopramide-induced hyperprolactinemia on the
hyaluronan acid in murine endometrium. Design: 80 adult (100 day-old) female virgin
mice were randomly divided into 8 groups of 10 animals each: 1 - group (nonovariectomized animals, non-Ovx); 2. group (ovariectomized animals, Ovx) treated with
the drug vehicle (0.2 ml NaCl 0.9% in distilled water), 3 - group (Ovx); 4 - group (Ovx)
received 200 μg metoclopramide dissolved in 0.2 ml NaCl 0.9% in distilled water; 5.
Group Ovx treated with 17β-estradiol; 6. Ovx animals treated with 17β-estradiol; 7. Ovx
treated with progesterone; and 8. Ovx treated with metoclopramide plus progesterone.
Vehicle and metoclopramide were administered intraperitoneally; the steroid hormones
were administered by gavage once daily at 10 a.m. during 50 consecutive days. In the
50th day, the animals were killed, the middle portions of the uterine horns were removed
and sectioned into 2 fragments; one of them was fixed in 10% buffered formaldehyde and
subjected to routine histologic processing for paraffin inclusion and further sectioning
and haematoxylin-eosin staining. The second fragment was prepared for hyaluronan acid
determination by an ELISA-like assay method. The results were expressed as mean ± SD
and were analyzed by ANOVA. Significance level was set at P<0.05. Results: we found
that the hyperprolactinemic state induced and replacement of estrogen and progestin
significant alterations on HA concentration of mouse uterus. Conclusion: Our results
suggest that replacement of estrogen and progestin may increase the hyaluronic acid in
metoclopromide-induced hyperprolactinemia in mice after castration.
P-15.
Effects of metoclopramide-induced hyperprolactinemia on the gene
expression of hyaluronan synthases in mouse uterine along the different
phases of the estrous cycle
* P<0.05 between DX and NoDX cohorts.
P-13.
Effects of metoclopramide-induced hyperprolactinemia on the on tibial
epiphyseal growth plate of ovariectomized rats after hormonal
replacement
Roberta B. Wolff, MSc2, Regina C. Teixeira Gomes, PhD1, Carina Verna, Dr2, Gabriela C.
Cristofani Maioral, MSc2, Thais C. Rampazo, Graduate Student2, Manuel J. Simões, PhD1,
Ricardo S. Simões, MSc3, José M. Soares Júnior, MD, Ph.D3. 1Department of
Morphology, São Paulo Federal University, São Paulo, Brazil; 2Department of
Gynecology and Climaterium, São Paulo Federal University, São Paulo, Brazil;
3
Department of Gynecology and Obstetrics, University of São Paulo Medical School of
Medicine, São Paulo, Brazil
Objective: To analyse the of metoclopramide-induced hyperprolactinemia on mice
epiphyseal disk after ovariectomy Design: 80 adult (100 day-old) female virgin mice
were randomly divided into 8 groups of 10 animals each: GI group (non-ovariectomized
animals, non-Ovx) and GII group (ovariectomized animals, Ovx) were treated with the
drug vehicle/day (0.2 ml NaCl 0.9% in distilled water), GIII group (Ovx) and GIV group
were treated with 6,7 μg/g metoclopramide/day dissolved in 0.2 ml NaCl 0.9% in distilled
water; GV group (Ovx) was treated with drug vehicle/day and 2ug/day 7β-estradiol; GVI
group (Ovx) was treated with 6,7 μg/g metoclopramide/day and 2ug/day 17β-estradiol;
VII group (Ovx) was treated with drug vehicle/day and 2mg/day progesterone and VIII
group (Ovx). was treated with 6,7 μg/g metoclopramide/day and 2mg/day
progesterone.Vehicle and metoclopramide were administered intraperitoneally; the steroid
hormones were administered by gavage once daily at 10 a.m. during 50 consecutive days.
In the 50th day, following euthanasia the animals were the tibia removed, which was fixed
in 10% formadehyde, decalcified (10% formic acid) and then submitted to histological
processing for inclusion in paraffin. The sections were stained by haematoxylin-eosin
(H.E.) evaluated by morphologic methods. The histomorfometric analysis of the disk
thickness of epiphyseal area was performed using the AxionVision 4.2, RL system (Carl
Zeiss) and AxioLab Standart 2.0 microscope. The results were evaluated through statistical
analysis by ANOVA tests. Results: The animals ovariectomized and treamented with
metoclopramide had significant decrease in the epiphyseal disk thickness when compared
to other groups. Conclusion: the morphologic results suggest that the metoclopramideinduced hyperprolactinemia may decrease the thickness of the ovariectomized epiphyseal
disk.
Regina C. Teixeira Gomes, PhD1, Carina Verna, Dr2, Gabriela C. Cristofani Maioral,
MSc2, Roberta B. Wolff, MSc2, Ricardo S. Simões, MSc3, Vivien J. Coulson-Thomas,
Dr4, Manuel J. Simões, PhD1, José M. Soares Júnior, MD, Ph.D2. 1Department of
Morphology, São Paulo Federal University, São Paulo, Brazil; 2Department of
Gynecology and Climaterium, São Paulo Federal University, São Paulo, Brazil;
3
Department of Gynecology and Obstetrics, University of São Paulo Medical School of
Medicine, São Paulo, Brazil; 4Department of Biochemistry, São Paulo Federal University,
São Paulo, Brazil
Objective: evaluate effects of metoclopramide-induced hyperprolactinemia on the gene
expression of hyaluronan synthases 1, 2 and 3 in mouse uterine. Design: 80 adult (100
days old) female virgin mice were randomly divided into two groups of 40 animals each:
control (Ctr), which received intraperitonela (IP) 0.2 ml of saline solution, and
experimental (HPrl), which received IP 6,7 μg/g metoclopramide. After 50 days the
animals were properly randomly divided into 8 groups of 10 animals, according to the
phase of the cycle: proestrus (Ctr and HPrl), estrus (Ctr and HPrl), metaestrus (Ctr and
HPrl) and diestrus (Ctr and HPrl). In the 50th day, one hour after the last drug or vehicle
injection, a vaginal smears evaluation was performed in order to verify the estrous cycle
phase. Following euthanasia, the uterine horns were removed, sectioned and immediately
frozen in liquid nitrogen for RNA extraction to detect tissue (HAS1, 2 and 3) by
Polymerase Chain Reaction Real Time. Blood was collected for the dosage of prolactin
and serum estrogen and progesterone using ELISA-like assay. The results were expressed
as mean ± SD and were analyzed by the ANOVA. Results: 80 adult (100 days old) female
virgin mice were randomly divided into two groups of 40 animals each: control (Ctr),
which received intraperitoneal (IP) 0.2 ml of saline solution, and experimental (HPrl),
which received IP 6,7 μg/g metoclopramide. After 50 days the animals were properly
randomly divided into 8 groups of 10 animals, according to the phase of the cycle:
proestrus (Ctr and HPrl), estrus (Ctr and HPrl), metaestrus (Ctr and HPrl) and diestrus (Ctr
and HPrl). In the 50th day, one hour after the last drug or vehicle injection, a vaginal
smears evaluation was performed in order to verify the estrous cycle phase. Following
euthanasia, the uterine horns were removed, sectioned and immediately frozen in liquid
nitrogen for RNA extraction to detect tissue (HAS1, 2 and 3) by Polymerase Chain
Reaction Real Time. And another part was fixed in 10% formol for immunohistochemical
evaluation of HAS1, 2 and 3. The results were expressed as mean ± SD and were analyzed
by the ANOVA. Conclusion: The analysis of immunohistochemistry showed that
hyaluronan synthases HAS1 and HAS2 increased in phases of proestrus, estrus and
metaestrus and HAS3 decreased during the proestrus and increased in phases of estrus and
metaestrus. And the gene expression increased HAS1 phases of estrus, metaestrus and
diestrus. And the gene expression of HAS2 and HAS3 was low.
43
Basic Science (continued) & Clinical Poster Presentations
P-16.
Study of gene expression of prolactin and prolactin receptor in the mice
uterus with metoclopramide-induced hyperprolactinemia throughout the
estrous cycle
Regina C. Teixeira Gomes, PhD1, Carina Verna, Dr2, Gabriela C. Cristofani Maioral,
MSc2, Roberta B. Wolff, MSc2, Ricardo S. Simões, MSc3, Edmund Chada Baracat, MD,
Ph.D3, Helena B. Nader, PhD4, José M. Soares Júnior, MD, Ph.D2. 1Department of
Morphology, Federal University of São Paulo, São Paulo, Brazil; 2Department of
Gynecology and Climaterium, São Paulo Federal University, São Paulo, Brazil;
3
Department of Gynecology and Obstetrics, University of São Paulo Medical School of
Medicine, São Paulo, Brazil; 4Department of Biochemistry, São Paulo Federal University,
São Paulo, Brazil
Objective: To evaluate the metoclopramide-induced hyperprolactinemia impact on the
expression of genes prolactin and prolactin receptor in mouse uterus during the estrous
cycle. Design: 80 adult (100 days old) female virgin mice were randomly divided into two
groups of 40 animals each: control (Ctr), which received intraperitonela (IP) 0.2 ml of
saline solution, and experimental (HPrl), which received IP 6,7 μg/g metoclopramide.
After 50 days the animals were properly randomly divided into 8 groups of 10 animals,
according to the phase of the cycle: proestrus (Ctr and HPrl), estrus (Ctr and HPrl),
metaestrus (Ctr and HPrl) and diestrus (Ctr and HPrl). Following euthanasia, the uterine
horns were removed and fixed in 10% formol. After subjected to histological processing
for inclusion in paraffin. The sections were stained by haematoxylin-eosin (H.E.)
evaluated by morphologic methods. The expression genes prolactin and prolactin receptor
was quantitative Reverse Transcriptase Polymerase Chain Reaction PCR Analysis Real
Time. The results were expressed as mean ± SD and were analyzed by the ANOVA.
Results: We found that the hyperprolactinemic state induced decrease at proestrus and
increase estrus the expression of genes prolactin and prolactin receptor, while increase the
expression of genes prolactin and decrease the expression of genes prolactin receptor.
Conclusion: The present results show that hyperprolactinemia induces estral cycledependent alterations on the expression of genes prolactin and prolactin receptor in mouse
uterus. These changes could conceivably help to explain some of the infertility problems
related to high prolactin circulating levels and/or the observed failures of embryo
implantation in hyperprolactinemic states.
P-17.
The gene expression prolactin and prolactin receptor’ study in mice
lactimal gland with metoclopramide-induced hyperprolactinemia
Carina Verna, Dr2, Regina C. Teixeira Gomes, PhD1, Gabriela C. Cristofani Maioral,
MSc2, Roberta B. Wolff, MSc2, Vivien J. Coulson-Thomas, Dr4, Helena B. Nader, PhD4,
Ricardo S. Simões, MSc3, José M. Soares Júnior, MD, Ph.D2. 1Department of
Morphology, São Paulo Federal University, São Paulo, Brazil; 2Department of
Gynecology and Climaterium, São Paulo Federal University, São Paulo, Brazil;
3
Department of Gynecology and Obstetrics, University of São Paulo Medical School of
Medicine, São Paulo, Brazil; 4Department of Biochemistry, Paulo Federal University, São
Paulo, Brazil
Objective: To evaluate the metoclopramide-induced hyperprolactinaemia impact on the
expression of genes prolactin and prolactin receptor in mouse lactimal gland. Design: 20
adult (100 days old) female virgin mice were randomly divided into two groups of 10
animals each: control (Ctr), which received intraperitoneal (IP) 0.2 ml of saline
solution/day, and experimental (HPrl), which received IP 6,7 μg/g/day
metoclopramide.The 50th day of treatment were anesthetized, sacrificed and removed the
lacrimal gland was fixed in Bouin, and then subjected to histological processing for
inclusion in paraffin. The sections were stained by haematoxylin-eosin (H.E.) evaluated
by morphologic methods. The histomorfometric analysis of the lacrimal gland was
performed using the AxionVision 4.2, RL system (Carl Zeiss) and AxioLab Standart 2.0
microscope. And a part of the lactimal gland were removed and the expression genes
prolactin and prolactin receptor was quantified Reverse Transcriptase Polymerase Chain
Reaction PCR Analysis Real Time. The results were submitted statistical analysis
ANOVA. Results: the metoclopramide-induced hyperprolactinemia determined
alterations morphologic and increased the expression of genes prolactin and prolactin
receptor in lacrimal gland. Conclusion: we found that the hyperprolactinemic state
induced increase the expression of genes prolactin and prolactin receptor on proestrus
phases. Possibly, this effect is related to reduction in estrogen and progesterone
production.
P-18.
Effects of metoclopramide-induced hyperprolactinemia on mice uterus
after hormonal replacement
Gabriela C. Cristofani Maioral, MSc2, Regina C. Teixeira Gomes, PhD1, Carina Verna,
Dr2, Roberta B. Wolff, MSc2, Mayara R. Silva, Graduate Studant2, Manuel J. Simões,
PhD1, Ricardo S. Simões, MSc3, José M. Soares Júnior, MD, Ph.D2. 1Department of
Morphology, São Paulo Federal University, São Paulo, Brazil; 2Department of
Gynecology and Climaterium, São Paulo Federal University, São Paulo, Brazil;
3
Department of Gynecology and Obstetrics, University of São Paulo Medical School of
Medicine, São Paulo, Brazil
Objective: To evaluate the effects of metoclopramide-induced hyperprolactinemia on
mice uterus after hormonal replacement with progesterone and 17β-estradiol. Design: 80
adult (100 day-old) female virgin mice were randomly divided into 8 groups of 10 animals
each: GI group (non-ovariectomized animals, non-Ovx) and GII group (ovariectomized
animals, Ovx) were treated with the drug vehicle/day (0.2 ml NaCl 0.9% in distilled
water), GIII group (Ovx) and GIV group were treated with 6,7 μg/g metoclopramide/day
44
dissolved in 0.2 ml NaCl 0.9% in distilled water; GV group (Ovx) was treated with drug
vehicle/day and 2ug/day 7β-estradiol; GVI group (Ovx) was treated with 6,7 μg/g
metoclopramide/day and 2ug/day 17β-estradiol; VII group (Ovx) was treated with drug
vehicle/day and 2mg/day progesterone and VIII group (Ovx). was treated with 6,7 μg/g
metoclopramide/day and 2mg/day progesterone. Vehicle and metoclopramide were
administered intraperitoneally; the steroid hormones were administered by gavage once
daily at 10 a.m. during 50 consecutive days. In the 50th day, the animals were killed, the
middle portions of the uterine horns were removed them was fixed in 10% buffered
formaldehyde and subjected to routine histologic processing for paraffin inclusion and
further sectioning and haematoxylin-eosin staining.The results were expressed as mean
± SD and were analyzed by ANOVA. Significance level was set at P<0.05. Results: we
found that the hyperprolactinemic state induced and replacement of estrogen and progestin
significant alteration mice uterus Conclusion: It was observed comparing the groups
treated with metoclopramide and / or hormones in the control group: treatment with
estrogen promoted the proliferation of the endometrium as the uterus of the other groups
were atrophied.
CLINICAL POSTER PRESENTATIONS
P-19.
How Do Breast Pain and Breakthrough Bleeding Associated with
Hormonal Treatments for Menopausal Symptoms Impact Postmenopausal Women’s Lives: Qualitative Interviews with Post-menopausal
Women in the USA, China, Mexico and Italy
Lucy Abraham1, Rob Arbuckle3, Lorraine Dennerstein4, Louise Humphrey3, Laura
Maguire3, Sebastian Mirkin2, James A. Simon, MD, CCD, NCMP, FACOG5, Tara
Symonds1, Steven Walmsley3. 1PRO Centre of Excellence, Pfizer Ltd, Tadworth, United
Kingdom; 2Clinical Sciences, Pfizer Inc, Collegeville, PA; 3Patient Reported Outcomes,
Mapi Values Ltd, Bollington, United Kingdom; 4Dept of Psychiatry and National Aging
Research Institute, Melbourne University, Parkville, VIC, Australia; 5Department of
Obstetrics and Gynecology, George Washington University, Washington, DC
Objective: Estrogen plus progestin therapies (EPT) represent the current standard of care
for post-menopausal women with a uterus for the treatment of symptoms associated with
menopause. While successfully treating climacteric symptoms, the presence of progestin
is necessary to prevent endometrial proliferation. Progestins contained in EPT are
associated with side effects such as breast pain/tenderness and vaginal spotting/bleeding.
The objective of this study was to conduct qualitative interviews with post-menopausal
women to better understand the patient experience of breast pain and vaginal bleeding
symptoms associated with EPT and to assess the impact of these symptoms on postmenopausal women’s health-related quality of life (HRQoL). Design: 59 post-menopausal
women in the USA (n=14), China (n=15), Mexico (n=15) and Italy (n=15) (aged 40-63)
taking EPT and experiencing breast pain and/or vaginal bleeding/spotting (47/59 were
experiencing both) participated in in-depth interviews concerning their experiences of
EPT and impact on HRQoL. Thematic analysis was conducted to identify concepts
describing the experiences of the participants using Atlas Ti. Results: In all 4 countries,
women described a variety of impacts that breast pain and breakthrough bleeding had on
their HRQoL. The largest impact was on sex life with many women avoiding sex or
limiting foreplay when experiencing symptoms, particularly in the USA and China. As
one women explained “They want to touch you…and you can’t let them do that because
of the pain that you’re in”. In terms of psychological wellbeing, some described feeling
angry or annoyed that they were experiencing these symptoms now they were postmenopausal, while a minority said bleeding made them feel normal “called ‘the old friend’
in Shanghai dialect, menses give me a cheering message that I won’t get old”. Of concern
to some women was that breast pain or bleeding was a sign of an underlying health
problem, such as cancer “what’s wrong with me? Maybe I - my two aunts died in one year
of breast cancer, so I say maybe I have cancer.” While some felt their symptoms had no
impact on their daily life, others described how symptoms limited their social life, ability
to exercise and do chores, and even their choice of clothing “I liked to wear white pants
a lot and since I take these kind of pills, and I started bleeding, well, I don’t wear them”.
Conclusion: In-depth interviews with a geographically diverse sample revealed how
breast pain and bleeding associated with taking EPT can impact HRQoL. The impact of
these side effects of EPT on post-menopausal women’s HRQoL should be a consideration
when reviewing treatment options for menopausal symptoms.
P-20.
Prediction of Osteoporosis & fracture risk in postmenopausal Emirate
women. Wafa Al Omari, Anna Karkanis, Jenan Rashid and N Nagelkerke
Tawam Hospital,Al Ain,UAE
Wafa R. Al Omari, MD, FRCOG1, Anna Karkanis1, Jenan Rashid1, Nickolas Nagelkerke2.
1
OBG, Tawam Hospital, Al Ain, United Arab Emirates; 2Community medicine, Faculty
of medicine, Emirates university, Al Ain, United Arab Emirates
Objective: To explore public awareness of osteoporosis and willingness to manage the
problem,with reference to a variety of socio-economic factors. To look for predictors &
associates of osteoporosis& high fracture risk in postmenopausal emirate women with
special reference to social factors in UAE,e.g high parity,birth spacing and sun exposure.
Design: Cross-sectional questionnaire study. The study was carried out in Tawam
hospital,Menopause clinic. The study involved 180 post menopausal Emirates women .
Interventions involved: Questionaire,blood tests, BMD, Fore FR calculator and
measurement of weight,height. Results: Age and Osteoscale: There is a positive relation
between Age and risk of lower BMD in postmenopausal women. Years after menopause
and Osteoscale: The earlier the menopause take place,the more increase in the risk of
NAMS11_Regular-LB_Abstracts-2 8/29/11 4:13 PM Page 14
lower BMD. Parity and osteoporosis: Increased parity lead to increase the risk of
osteoporosis. Duration of breast feeding and osteoscale: There is no relation between
duration of breast feeding and bone density. BMI and osteoscale: Obesity is common
among postmenopausal Emirati women with a total mean of BMI of 30.osteoporosis
decreased with increase in wt . Medical disorder and Osteoscale: From all medical
disorder, chronic renal disease is the most common disease that affect bone density
adversily. Medication and Osteoscale: Steriods is the most common medication that affect
bone density adversily. Cancer drugs has no significant effect on bone density. Sun
Exposure,Habits and Osteoscale: All women did not smoke,and have a relatively short
duration of exposure to sun light and even upon exposure they were heavily covered.
However no relation found between duration of sun exposure and Osteoscale. Biochemical
markers and Osteoscale There is no correlation between the serum concentration of 25
OHD,calcium level and alkaline phosphatase when related to osteoscale. Conclusion: In
postmenopausal Emirate Women abnormal bone health was present in 66 % of patients.
More attention to be paid to build up peak bone density before the age of 20. Modifiable
factors has to be looked at from a different angle as duration of sun exposure was not
related to bone health. Type of culture & costume limit sun exposure benefit.
P-21.
Prevalence of depression and associated factors in climacteric in the
“Health Project of Pindamonhangaba” (PROSAPIN)
Wendry M. Pereira, master1, Débora P. Rezende1, Elaine A. Pereira1, Ana Carolina B.
Schmitt2, Maria Regina A. Cardoso1, José M. Aldrighi, PhD1. 1School of Public Health,
University of São Paulo, São Paulo, Brazil; 2School of Medicine, University of São Paulo,
São Paulo, Brazil
Objective: To estimate the prevalence of depression and to identify its associated factors
among women in climacteric. Design: The study was cross-sectional, including 875
women aged 35 - 65 years selected by a probabilistic sampling technique in
Pindamonhangaba city, Brazil. A self-reported questionnaire was applied including
variables related to socio-demographics characteristics, lifestyle, gynecological and
obstetric history, morbidity and depression, investigated by the Beck’s Inventory. The
prevalence of depression was estimated and a multiple logistic regression model was used
to identify its associated factors. Stata, version 10.1, was used in the analyses. Results:
The prevalence of the depression was 33.7% (95%IC: 30.4% – 37.3%). The associated
factors found were: poor sleep quality (p<0.001), anguish feelings (p<0.001) and
insecurity (p<0.001), obstructive sleep apnea (p=0.002), hypertension (p=0.01), referred
cardiac problem (p=0.03) and falls in the last six months (p=0.04). Conclusion:
Depression affected more than a third of women and its associated factors were sleep
quality, morbidities and feelings of anguish and insecurity.
P-22.
Associated Factors With Insomnia in Climateric Women: PROSAPIN
(Pindamonhangaba Project Health)
Elaine A. Pereira1, Ana Carolina B. Schmitt2, Wendry P. Pereira1, Debora P. Rezende1,
Maria Regina A. Cardoso1, José M. Aldrighi, PhD1. 1School of Public Health, University
of São Paulo, São Paulo, Brazil; 2School of Medicine, University of São Paulo, São Paulo,
Brazil
Objective: To estimate the prevalence of insomnia and to identify associated factors in
climacteric women. Design: Cross-sectional study with 875 women aged 35 to 65 years
registered at the Family Health Strategy from Pindamonhangaba city (São Paulo, Brazil)
selected by a probabilistic sampling technique. The study estimated the prevalence of
symptoms suggestive of insomnia through information contained in the Beck Depression
Inventory. Thus, insomniacs were considered women who referred difficulty falling
asleep, keeping asleep or early awakening. To evaluate the associated factors, the women
were asked to respond a questionnaire on socio-demographic characteristics, lifestyle,
gynecological history and clinical morbidity and medication and their weight, height and
waist circumference were measured. Analysis was performed by a multiple logistic
regression model using Stata 10.1. Results: Insomnia was reported by 36.6% (95%IC:
33.1 – 40.1) of the study women and the factors associated were: sleeping less than six
hours per night (p=0.043), the presence of poor sleeping quality (p<0.001), polycystic
ovary syndrome (p=0.002) and occupational physical activity above the average
population (p=0.002). Conclusion: The prevalence of insomnia was high in climacteric
women and it was associated with sleeping less than six hours and with poor sleeping
quality, the presence of polycystic ovary syndrome and physical activity.
P-23.
Over- and Under-Reporting of Diabetes Mellitus and Hypertension in
Climacteric Women in the “Health Project of Pindamonhangaba”
(PROSAPIN)
Ana Carolina B. Schmitt2, Maria Regina A. Cardoso1, Wendry P. Pereira1, Elaine A.
Pereira1, Debora P. Rezende1, Rubia G. Guarizi1, Mayra C. Dellu1, Erika Flauzino1, José
M. Aldrighi, PhD1. 1School of Public Health, University of São Paulo, São Paulo, Brazil;
2
School of Medicine, University of São Paulo, São Paulo, Brazil
Objective: To estimate and compare the prevalence of hypertension and diabetes mellitus
referred and measured in climacteric women. Design: The study was cross-sectional and
investigated a probabilistic sample of 875 women aged 35 to 65 years from
Pindamonhangaba city, Brazil. It was asked if they were aware of suffering from
hypertension and diabetes mellitus. In addition, both the blood pressure and blood glucose
were measured. Women were considered hypertensive when their pressure levels were
greater than or equal to 130x85 mmHg, and were considered diabetic those with glucose
levels greater than or equal to 100mg/dl, or even the ones under drug therapy. The
prevalence of hypertension and diabetes were estimated with their 95% confidence
intervals (95%CI) and the Kappa statistic was used to evaluate the agreement between the
morbidities referred and measured. Results: Measured hypertension was present in
36.69% of women (95%CI: 33.24 - 40.13%) and it was referred by 40.91% (95% CI:
37.37 – 44.46%). Diabetes was measured in 22.82% of women (95%CI: 19.27 – 26.37%)
and 10.84% (95%CI: 8.57 – 13.10%) referred suffering from it. The Kappa coefficient for
hypertension was 34.54% (95%CI: 27.37 – 41.71%) and for diabetes was 42.89%
(95%CI: 34.89 – 50.89%). Conclusion: Hypertension was overestimated in this
population while diabetes was underestimated. Thus, many women may be missing
opportunities for receiving adequate health care assistance.
P-24.
Transdermal estradiol gel for the treatment of symptomatic
postmenopausal women
David F. Archer, MD1, James H. Pickar2, Dipali C. MacAllister3, Michelle Warren2. 1Jones
Institute for Reproductive Medicine, Eastern Virginia Medical School, Norfolk, VA;
2
Columbia University Medical Center, New York, NY; 3ASCEND Therapeutics, Herndon,
VA
Objective: To determine the efficacy, safety, and lowest practical dose of a transdermal
estradiol gel for the treatment of symptomatic, postmenopausal women. Design: Healthy,
postmenopausal women with at least 7 moderate to severe hot flushes per day or at least
an average of 50 or 60 per week (depending on the trial) were randomized to 1.5 mg
(n=73) or 0.75 mg (n=75) of estradiol in a transdermal 0.06% gel or placebo (n=73) in a
phase 3 study, or to 0.375 mg (n=119) or 0.27 mg (n=118) of estradiol in a transdermal
0.03% gel or placebo (n=114) in a phase 4 study. Hot flush frequency and severity,
responders for frequency, vaginal maturation index (VMI), and adverse events (AEs) were
evaluated. A lower concentration of estradiol gel (0.03%) was used in the phase 4 study
instead of the currently approved 0.06% concentration used in the phase 3 study, so that
lower amounts of estradiol (0.375 mg and 0.27 mg) could be dispensed. Results: A total
of 89% (196/221) and 79% (277/351) of subjects completed the phase 3 and 4 studies,
respectively. Demographics and baseline hot flush number and severity were not notably
different between groups within each study. Estradiol and estrone levels increased with
estradiol gel application. Frequency of moderate to severe hot flushes and severity of all
hot flushes significantly decreased compared with placebo at weeks 4 and 12 with 0.75
mg and 1.5 mg estradiol in the phase 3 study and with 0.375 mg estradiol in the phase 4
study. The placebo response was different between the two studies, and the percentages
of responders with the estradiol gel doses studied were higher than with placebo. The
overall subject responder rates were generally lower in the phase 4 study than those in the
phase 3 study with the approved gel with 0.75 mg estradiol (Table). Significant shifts
(P<0.001) in the VMI from baseline to week 12 compared with placebo were also
observed with 0.75 mg and 1.5 mg estradiol in the phase 3 study; and significant
improvements in the VMI (P<0.001), increases in superficial cells (P=0.005), and
decreases in parabasal cells (P=0.002) were seen with 0.375 mg estradiol compared with
placebo in the phase 4 study (no significant changes with 0.27 mg estradiol). The
percentages of subjects who experienced at least 1 treatment-emergent AE (TEAE) were
78.7%, 83.6% and 69.9% with 0.75 mg estradiol, 1.5 mg estradiol, and placebo,
respectively (phase 3); and 49.6%, 54.3% and 54.0% with 0.375 mg estradiol, 0.27 mg
estradiol, and placebo, respectively (phase 4). The most frequently reported TEAEs (in
≥5% of subjects) were headache, infection, breast pain, and nausea in the phase 3 study;
and (in ≥2% of subjects) were insomnia and headache in the phase 4 study. A similar
number of patients discontinued due to AEs in both studies. Three serious AEs not
considered related to treatment were reported with estradiol in the phase 3 study, whereas
3 serious AEs were reported with placebo and none with estradiol in the phase 4 study.
No deaths occurred in either study. Conclusion: A transdermal estradiol gel with 0.75 mg
estradiol effectively reduced the frequency and severity of moderate to severe hot flushes,
improved VMI, and was well tolerated. Transdermal gel with 0.75 mg of estradiol
(EstroGel® 0.06%, 1.25 g of gel) is currently indicated in the treatment of moderate to
severe vasomotor symptoms and moderate to severe symptoms of vulvar and vaginal
atrophy due to menopause. The overall efficacy, safety, and responder rates of the 4 studied
estradiol doses considered with the currently available formulation, confirm that the
transdermal gel with 0.75 mg of estradiol is the lowest practical dose for treatment of
symptomatic, postmenopausal women. The data from the Phase 4 study do not preclude
further investigation of a lower-dose estradiol gel than what is currently available.
Table. Percentage of Responders for Hot Flush Frequency*
*Responders were subjects with ≥50% reduction from baseline in moderate to
severe hot flushes.
45
NAMS11_Regular-LB_Abstracts-2 8/29/11 4:13 PM Page 15
Clinical Poster Presentations (continued)
P-25.
Safety and Tolerability of Bazedoxifene/Conjugated Estrogens in
Postmenopausal Women: Findings From a 1-Year, Randomized, Placeboand Active-controlled, Phase 3 Trial
David F. Archer, MD1, Rogerio A. Lobo2, Kaijie Pan3, Arkadi A. Chines3, Sebastian
Mirkin3. 1Clinical Research Center, Eastern Virginia Medical School, Norfolk, VA;
2
Columbia University Medical Center, New York, NY; 3Pfizer Inc, Collegeville, PA
Objective: The tissue selective estrogen complex (TSEC) pairing bazedoxifene (BZA)
with conjugated estrogens (CE) has been shown to be effective in treating menopausal
symptoms and preventing osteoporosis while protecting the endometrium in women with
a uterus. This randomized, double-blind, placebo- and active-controlled, phase 3 study
(Selective estrogens, Menopause, And Response to Therapy [SMART]-5 trial) was
conducted to evaluate the efficacy and safety of BZA/CE compared with placebo,
medroxyprogesterone (MPA)/CE, and BZA monotherapy in nonhysterectomized
postmenopausal women. Here we report findings related to the endometrial safety and
overall safety/tolerability profile of BZA/CE during 1 year of treatment. Design:
Postmenopausal women (aged 40-65 years) with an intact uterus were randomized to
receive daily oral doses of BZA 20 mg/CE 0.45 mg (n = 335), BZA 20 mg/CE 0.625 mg
(n = 368), BZA 20 mg (n = 169), MPA 1.5 mg/CE 0.45 mg (n = 149), or placebo (n =
354). Endometrial safety was evaluated by the incidence of endometrial hyperplasia as
measured by endometrial biopsy at 1 year. Adverse events (AEs) were recorded
throughout the study. Breast tenderness and uterine bleeding (sanitary protection required)
or spotting (light or no sanitary protection required) were recorded in daily dairies. Noncumulative and cumulative rates of amenorrhea (no bleeding or spotting) for 4-week
periods over a year were summarized. Results: At Year 1, the incidence of endometrial
hyperplasia with BZA 20 mg/CE 0.45 mg (0.30%) and BZA 20 mg/CE 0.625 mg (0.27%)
was similar to that with BZA 20 mg (0%), MPA 1.5 mg/CE 0.45 mg (0%), and placebo
(0.28%). The overall incidence of AEs, treatment-emergent AEs (TEAEs), and serious
AEs was similar among treatment groups. There was a higher incidence of AEs leading
to study discontinuation in the MPA 1.5-mg/CE 0.45-mg group (14.1%) than in the BZA
20-mg/CE 0.45-mg (7.6%), BZA 20-mg/CE 0.625-mg (7.0%), BZA 20-mg (7.0%), or
placebo groups (7.0%; overall P = 0.012). During Year 1, the percentage of subjects who
reported at least 1 day of breast tenderness during 4-week cycles with BZA 20 mg/CE 0.45
mg (3.0%-9.4%) and BZA 20 mg/CE 0.625 mg (2.6%-9.1%) was similar to that with
placebo (2.0%-8.6%) and lower than that with MPA 1.5 mg/CE 0.45 mg (9.4%-24.3%).
For both BZA/CE doses, the rates of spotting (0.5%-5.8%) and bleeding/spotting (0.5%6.2%) during 4-week cycles were generally low and similar to those with placebo
(1.3%-4.8% and 1.6%-4.8%, respectively). MPA 1.5 mg/CE 0.45 mg was associated with
higher rates of spotting (8.2%-24.1%) and bleeding/spotting (8.8%-25.6%) compared
with the BZA/CE and placebo groups. Cumulative rates of amenorrhea for consecutive
4-week cycles in women treated with BZA 20 mg/CE 0.45 mg (87.9%-98.3%) and BZA
20 mg/CE 0.625 mg (84.9%-98.7%) were similar to those in women treated with placebo
(83.9%-98.4%) and higher than those in women treated with MPA 1.5 mg/CE 0.45 mg
(54.4%-91.2%). Conclusion: BZA 20 mg/CE 0.45 and 0.625 mg were associated with a
favorable endometrial safety and overall safety profile over 12 months. The tolerability
profile of BZA/CE as measured by rates of amenorrhea and breast tenderness was not
different from placebo and more favorable than MPA/CE.
P-26.
Efficacy of a novel SERM, ospemifene, in the treatment of dyspareunia
symptoms associated with postmenopausal vulvovaginal atrophy
Gloria Bachmann, Dr.1, Steven R. Goldstein, MD, FACOG, CCD, NCMP2, Vivian Lin3,
David Portman, MD4, James Liu5, Shelli Graham6, Michele Giliberti6, James A. Simon,
MD, CCD, NCMP, FACOG7. 1UMDNJ-Robert Wood Johnson Medical School, New
Brunswick, NJ; 2New York University School of Medicine, New York, NY; 3QuatRX
Pharmaceuticals Company, Ann Arbor, MI; 4Columbus Center for Women’s Health
Research, Columbus, OH; 5MacDonald Women’s Hospital, Cleveland, OH; 6Clinical
Development, Shionogi Inc, Florham Park, NJ; 7The George Washington University
School of Medicine, Washington DC, DC
Objective: Currently, only estrogen-based preparations have received regulatory approval
for prescription treatment of vulvovaginal atrophy (VVA) in postmenopausal women;
therefore, exploring alternative treatments for VVA is imperative. Ospemifene, a novel,
selective estrogen receptor modulator (SERM), is unique compared with other SERMs
due to its estrogenic activity in the vaginal epithelium and is under investigation in
postmenopausal women with VVA symptoms. This study assessed the efficacy, safety,
and tolerability of ospemifene 60 mg/d in the treatment of VVA symptoms in
postmenopausal women. Design: This 12-wk, randomized, double-blind, placebocontrolled, parallel-group study included 919 subjects. Two study populations were
analyzed: intent-to-treat (ITT), the primary analysis, and per protocol (PP). Women (4080 years of age) were assigned to one of 2 VVA symptom strata (vaginal dryness or
dyspareunia) based on their self-reported most bothersome VVA symptom (MBS);and
within each stratum were randomized 1:1 to receive either ospemifene 60 mg/d or placebo.
Data from each stratum were independently analyzed. All subjects were provided with a
nonhormonal vaginal lubricant to be used as needed (PRN). For each stratum, co-primary
efficacy endpoints were measured for change from baseline to Wk 12 (LOCF) in: vaginal
pH, % superficial cells and % parabasal cells in the maturation index, and the severity of
the MBS. This abstract reports the dyspareunia stratum results. Results: At Wk 12
ospemifene demonstrated significant efficacy vs placebo for each co-primary endpoint.
Changes in the ITT population for vaginal pH (LS mean),% of superficial cells (median),
and % of parabasal cells (LS mean) all were p<0.0001 (Table 1); a significant effect was
observed as early as 4 wks. Significant mean improvement was also observed for the
MBS, dyspareunia (p=0.0001) at Wk 12. A higher percentage of subjects treated with
46
ospemifene reported no, or mild dyspareunia and self-reported symptom severity that
improved by 2-3 points on a 4-point Likert scale in 52.8% of ospemifene vs 38.8% of
placebo subjects. The PP analysis also demonstrated statistically significant findings for
each co-primary endpoint, confirming ITT analysis. The % of subjects with at least 1
adverse event (in the ITT population) at Wk 12 for both strata combined is summarized
in Table 2. Discontinuation rates were similar in the ospemifene and placebo groups,
10.2% vs 11.6%, respectively. Endometrial histology assessments showed no cases of
hyperplasia and 2 (1.0%) cases of active proliferation in the ospemifene group vs 0% in
the placebo group. Vaginal bleeding was reported in 2 (0.4%) and 4 (0.9%) subjects in the
ospemifene and placebo groups, respectively. One subject in the ospemifene group
experienced a deep vein thrombosis following an 8-hour car ride and was discontinued
from the study. Conclusion: In postmenopausal women with self-reported MBS of
dyspareunia, this unique study demonstrated that, despite the PRN use of lubricants,
treatment with ospemifene 60 mg/d demonstrated clinically and statistically significant
efficacy and was well tolerated.
Table 1 Change from BL to WK 12/LOCF (ITT Analysis)*
* Similar results were reported for the PP analysis
Table 2 Adverse Events
P-27.
Hot Flashes, Sleep Complaints and Depressed Mood in Midlife Women
Jessica P. Brown1, Patti E. Gravitt2, J. Kathleen Tracy1. 1Epidemiology and Public Health,
University of Maryland School of Medicine, Baltimore, MD; 2Epidemiology, Johns
Hopkins School of Public Health, Baltimore, MD
Objective: Prior research has shown that 20% of midlife women report sleepiness
consistently interferes with daily life, including augmenting symptoms of depression and
anxiety. Menopausal women with chronic nighttime awakening report significantly lower
health related quality of life in both physical and mental health domains. Here we
examined the relations among hot flashes, sleep complaints and depressed mood as part
of a larger study on midlife women’s genital health. Design: Cross-sectional data were
obtained from 179 women (ages 35-60, 79% white). Hot flash experience was obtained
from a comprehensive menopausal symptom checklist; it was coded as ever/never as well
as ever/never within the past year. Sleep complaints were assessed by the Pittsburgh Sleep
Quality Index (PSQI) and depressed mood was assessed with the Center for
Epidemiological Studies-Depression scale (CES-D). A PSQI total score of 5 or greater
suggests clinically meaningful sleep complaints. A CES-D score of 16 or greater indicates
depressed mood. Results: The experience of hot flashes was significantly related to the
total PSQI score for both ever having experienced a hot flash (t=3.60, p<.001) and for
having hot flashes within the past year (t=3.24, p=.001). Depressed mood was not
significantly related to hot flashes, but was strongly correlated with PSQI total score
(r=.64, p<.001), with 25% of the sample reporting both elevated PSQI and CES-D scores.
Self-rated sleep quality, somnolent medication use, and habitual sleep efficiency did not
vary by hot flash experience either ever or within the past year (all p’s>.05). However, ever
experiencing hot flashes was related to shorter sleep duration (chi-square=9.55, p = .023),
longer sleep latency (chi-square=8.26, p=.041), more frequent daytime dysfunction (chisquare = 11.86, p= .008), and greater sleep disturbance (chi-square = 8.46, p=.015). When
examining participants with hot flashes within the past year, sleep duration and daytime
dysfunction were no longer significant (p’s>.05), whereas longer sleep latency and sleep
disturbance remained significantly more likely in women who reported hot flashes in the
past year. Among hot flash sufferers, those reporting less than 7 hours of sleep per night
were significantly more likely to report an elevated CES-D score, (chi-square = 7.29,
p=.007). Women who reported ever having hot flashes and who experienced daytime
dysfunction somewhat or at least weekly were significantly more likely to have an elevated
CES-D score (chi-square=8.68, p=.003). Among women who reported hot flashes within
the past year, however, there was no relation between sleep latency or sleep disturbance
and elevated CES-D score (p’s>.05) Conclusion: Midlife women with hot flashes
reported numerous sleep complaints, but not all these sleep complaints were related to
depressed mood. In fact, there was no association with difficulty falling asleep or frequent
trouble sleeping and depressed mood in women with recent hot flashes. Clinically, the
experience of hot flashes could be used to prompt a discussion of good sleep hygiene to
mitigate the potential for future sleep or mood disturbance.
P-28.
Perimenopause and Menopause Support Program
Carol Caico, Ph.D., N.P.. Nursing, NYIT, Seaford, NY
Objective: The hypothesis was that women who go through a structured support group
will be better prepared to cope with symptoms and be better informed on what health
care choices they would make. The findings supported the benefits of being part of a
perimenopause and menopause support group and the information learned during the 10
weeks helped women to feel they are not unique in the way they are coping with this
period of a woman’s life. Design: Perimenopause and menopause is a period in a womens’
lives associated with many physical and emotional changes. The severity of the symptoms
range from mild to severe and can affect relationships with partners, friends, and
coworkers. Symptomatic women often try to suffer alone or do not feel supported during
this sometimes long period of transition. This study will provide a forum of support for
these women which will increase their knowledge and power to effectively cope with this
transition of life. The support program was conducted by a Women’s Health Nurse
Practitioner who holds a certificate as a Menopause Clinician as well as a Specialist in
Adult and Psychiatric Mental Health. Two questionnaires were completed at the first
support group. One of the questionnaires used was developed by the PI when she
completed her doctoral dissertation. The other questionnaire is the Quality of Life
questionnaire developed by Wulf H. Utian. Subjects were invited to attend the support
program with inclusion criteria that they be English speaking women between the ages of
45-60 who are currently experiencing symptoms or difficulty coping with perimenopause
or menopause. Fliers were distributed to many OB-GYN offices as well as local hospitals
and advertisement was be put in local papers. The program was held weekly for 10
consecutive weeks and participants signd a consent which stated that they attend at least
7 or the 10 sessions and that the information attained from the meeting would be used for
research. The consent also informed the women that any information used in research
would assure anonymity. The venue for the support program was at a large community
hospital education center who agreed to provide refreshments for all sessions. The same
questionnaires were answered by participants at the end of the sessions. This was a
phenomenological study of women living through symptoms of perimenopause and
menopause.The researcher also started each meeting with a topic that was used as
education for the women, utilizing NAMS slides, and then women were free to talk about
any topic pertaining to what they were experiencing. This was to be a triangulated study
as there was a qualitative study based on themes from the sessions and a quantitative
analysis of questionnaires from the start of the program correlated with the questionnaires
at the end. Results: The findings supported the benefits of being part of a perimenopause
and menopause support group and the information learned during the 10 weeks helped
women to feel they are not unique in the way they are coping with this period of a
woman’s life. Another form which asked for the women to make comments on the
program as the researcher found that the during the program, questionnaires that were
used would not show significant change due to the support groups therefore the
quantitative piece did not indicated significance. The information gleaned from the field
notes from each sessionand the form that allowed the participants to anonymously fill out
the comment form demonstrated overwhelmingly positive results. Conclusion: The
information from this research confirmed that support groups are very important during
this period in women’s life and the research on the topic found many on-line lay support
but not many face to face support groups let by experts.
P-29.
Needs Assessment of American and Canadian Obstetrics and Gynecology
Residents Regarding Menopause Education: Areas for Improvement and
Learning Preferences
Mindy S. Christianson, MD1, Jennifer A. Ducie, M.D.1, Kristiina Altman, M.D.2,1, Wen
Shen, M.D.1. 1Gynecology and Obstetrics, Johns Hopkins University School of Medicine,
Baltimore, MD; 2Obstetrics and Gynecology, Johns Hopkins Bayview Medical Center,
Baltimore, MD
Objective: To understand the current teaching of menopause medicine in American and
Canadian Obstetrics and Gynecology (OB/Gyn) residency programs. In particular, as
curriculum developers, we sought to identify specific areas for improvement and assess
learner preferences for different educational methods. Design: Our team developed and
piloted a 24-item web-based survey. We then sent an e-mail message to all American and
Canadian OB/Gyn residency directors in April, 2011, inviting them to complete the webbased survey and forward it to their current residents. While program directors were
supplied with the web-link to the survey, they were requested to reply with how many
residents were forwarded the survey link. This survey is still actively in progress with
planned reminders scheduled at two- and four-week intervals prior to closing the survey.
Results: Of 311 residency program directors contacted via e-mail, 34 (10.9%) confirmed
forwarding the survey to their residents. Based on program director responses, 693
residents received the survey with 306 residents completing the survey for a response rate
of 44.1%. Of those completing the survey, 28.3% were first-year residents, 19.8 % secondyear, 25.4% third-year, 15.9% fourth-year residents and 10.6% program directors. When
asked to rank their experience during residency among the areas of gynecology, obstetrics,
reproductive endocrinology, menopause medicine and gynecologic oncology, 59.4% of
residents reported they had the least amount of experience in menopause. The majority of
residents reported they had limited knowledge and needed to learn more about these
aspects of menopause medicine: pathophysiology of menopause symptoms (62.2%),
hormone therapy (60.8%), non-hormone therapy (73.9%), bone health (60.0%),
cardiovascular disease (64.1%) and metabolic syndrome (62.3%). Similarly, a majority of
residents reported being not comfortable/barely comfortable in managing patients in these
areas: pathophysiology of menopause symptoms (59.3%), hormone therapy (66.4%), nonhormone therapy (67.9%), bone health (60.6%), cardiovascular disease (62.1%) and
metabolic syndrome (60.7%). When asked to rate the most preferred modalities to learn
about menopause, the top choice was supervised clinics (53.7%), followed by formal
lectures (21.9%), case presentations (21.4%), small groups (16.4%), web-based learning
(8.4%) and independent reading (6.0%). Only 15.2% of residents reported their program
had a formal menopause medicine learning curriculum and 15.6% have a defined
menopause clinic as part of their residency. Conclusion: Current American and Canadian
OB/Gyn residency training is deficient in menopause medicine education. Based on
preliminary results of our survey, most residency programs are not fulfilling the
educational goals of their residents in key menopause issues. A majority of residents
indicated they have only limited knowledge of common clinical menopause topics and are
barely comfortable in managing patients with menopause-specific problems. A curriculum
is needed to increase knowledge in the areas of pathophysiology of menopausal
symptoms, hormone and non-hormone therapy, bone health, cardiovascular disease and
metabolic syndrome. While supervised clinical experience is preferred by most residents
as a means to learn how to manage menopausal patients, this opportunity is lacking with
approximately 15% of residents reporting a defined menopause clinic as part of their
curriculum.
P-30.
Reductions in Brain Blood Flow During Hot Flashes in Postmenopausal
Women
Craig Crandall, Ph.D.1,2, Rebekah A. Lucas, Ph.D.1,2, Matthew S. Ganio, Ph.D.1,2, James
Pearson, Ph.D.1,2. 1Internal Medicine, University of Texas Southwestern Medical Center,
Dallas, TX; 2IEEM, Texas Health Presbyterian Hospital Dallas, Dallas, TX
Objective: Lightheadedness is occasionally reported during hot flashes. Such a response
may be due to reductions in brain blood flow during the hot flash, although it is unknown
whether this occurs. This study tested the hypothesis that hot flashes are accompanied by
a reduction in brain blood flow in postmenopausal women. Design: Eleven healthy,
normotensive, postmenopausal women prone to having frequent hot flashes (Age: 53±3
years, Weight: 62±6 kg; BMI: 24±2 kg; mean±SD) rested in the supine position in a
temperature-controlled laboratory (~25°C) for approximately 120 minutes while waiting
for hot flashes to occur. The onset of each hot flash was objectively identified by an abrupt
increase in sternal skin blood flow (laser Doppler flowmetry) and/or sternal sweat rate
(capacitance hygrometry), and was subjectively identified by the subject pressing a switch
at the beginning and end of each hot flash. Brain blood flow was evaluated via transcranial
Doppler of middle cerebral artery blood velocity (MCAvmean) prior to and throughout
hot flashes. Each hot flash was divided into 8 segments of equal duration, with the average
MCAvmean being obtained for each segment. For each hot flash, the segment with the
lowest MCAvmean was identified and was quantified as a percent reduction relative to
MCAvmean prior to that hot flash. Hot flashes were categorized as either “responders”
or “non-responders”, with the criterion for a responder being ≥10% reduction in
MCAvmean, relative to pre-hot flash baseline, in at least one segment during the hot flash.
Results: Twenty-eight hot flashes were evaluated amongst these 11 subjects. Seventeen
of these hot flashes exhibited at least a 10% reduction in MCAvmean and thus were
categorized as responders. The average decrease in MCAvmean for the responder group
of flashes was 19±5% (mean±SD; range: 10 to 31%), while the average decrease in
MCAvmean for the non-responder group of flashes was only 4±3% (range: 0 to 8%;
P<0.001 between responder and non-responder flashes). Conclusion: These data
demonstrate that approximately 60% of hot flashes are accompanied by a clear reduction
in brain blood flow. Based upon these findings, it is possible that lightheadedness during
hot flashes is due to inadequate cerebral perfusion and thus cerebral oxygenation. The
mechanism(s) responsible for the reduction in brain blood flow during the postmenopausal
hot flash warrants further investigation. Supported by NIH Grant AG030189
P-31.
Symptom clusters across the menopausal transition and postmenopause:
observations from the Seattle Midlife Women’s Health Study
Lori A. Cray, PhD1,2, Ellen S. Mitchell, PhD2, Jerald R. Herting, PhD3,2, Nancy F. Woods,
PhD2. 1College of Nursing, Seattle University, Seattle, WA; 2School of Nursing, University
of Washington, Seattle, WA; 3Sociology, University of Washington, Seattle, WA
Objective: To differentiate subgroups of women across the menopausal transition stages
and postmenopause who experience similar symptom clusters. Design: A secondary data
analysis of the Seattle Midlife Women’s Health Study. Sample: participants who provided
self-report data on symptoms experienced between 1990 and 2005. Latent class analysis
(LCA) two-level mixture modeling was used to identify subgroups of women who
experienced similar clusters of vasomotor, sleep, pain, cognitive, mood and tension
symptoms. Results: Three subgroups of women were identified: 1) asymptomatic
subgroup (80.2%); 2) highly symptomatic hot flash subgroup (5.2%); 3) low symptomatic
hot flash subgroup (14.7%). Women in the highly symptomatic hot flash subgroup also
experienced moderate sleep and pain symptom clusters, while women in the low
symptomatic hot flash subgroup experienced moderately higher clusters of sleep, pain,
mood, cognitive and tension symptoms. Conclusion: Although intervention studies tend
to target only one symptom, this analysis demonstrates that women experience clusters of
symptoms with varying degrees of severity. Shifting the focus from single symptoms to
symptom clusters will facilitate the identification of the unique symptom experience for
individual women.
47
NAMS11_Regular-LB_Abstracts-2 8/29/11 4:13 PM Page 17
Clinical Poster Presentations (continued)
P-32.
Effectiveness of Two Doses of a Monthly Oxybutynin Vaginal Ring in
Menopausal Women with Symptoms of Overactive Bladder
Sue E. Dasen, MS1, Kathleen Z. Reape, MD1, Howard I. Hait, MS2. 1Teva Women’s Health
Research & Development, Horsham, PA; 2Edenridge Associates, LLC, Wilmington, DE
Objective: As part of a larger Phase 2 clinical trial in adult women with overactive bladder
(OAB) and symptoms of predominant or pure urge incontinence, urinary urgency, and
elevated urinary frequency, a targeted subset analysis of menopausal women was
conducted to evaluate the effectiveness of two doses of a monthly oxybutynin (oxy)
vaginal ring (VR) compared to placebo. Design: In this Phase 2, multicenter, randomized,
double-blind, placebo-controlled study of both pre- and post-menopausal women aged
21.3 to 85.7 years, subjects were randomized to one of three treatment groups (placebo
VR, 4 mg/day oxy VR, or 6 mg/day oxy VR) at 68 investigational sites in the US and
Canada. Randomized subjects entered a three-week placebo VR run-in period, during
which they completed a 3-day OAB voiding diary. Upon successful completion of the
run-in phase, eligible subjects entered a 12-week treatment period, during which OAB
voiding diaries were completed prior to study visits at Weeks 4, 8, and 12. Vaginal rings
were changed once a month during the treatment period. The primary measure of efficacy
was the change from baseline to Week 12 (end-of-treatment) in the total weekly number
of incontinence episodes, with the two active treatment groups each being compared to
placebo. Among the 719 randomized participants was a subset of 249 post-menopausal
subjects (87 received placebo VR, 87 received oxy 4 mg/day VR, and 75 received oxy 6
mg/day VR) who met the following criteria at the end of the run-in period: >10 urge
incontinence episodes per week, average urinary frequency of > 8 voids/24 hours and
average total void volume of < 3.0 L/24 hours. The purpose of this analysis was to evaluate
the consistency of treatment effects in a post-menopausal subject population with a most
rigidly defined baseline symptomatology. Results: Both active treatment groups
demonstrated statistically significant reductions in the total weekly number of
incontinence episodes from baseline to the end-of-treatment, when compared to placebo.
The mean change for the oxy 4 mg/day VR was -16.90, p=0.0172; the mean change for
the oxy 6 mg/day VR was -16.36, p=0.0246, while the mean change for those women on
placebo was -12.63. These results were similar to what was observed in the overall study
population, i.e., regardless of menopausal status. Conclusion: In this Phase 2 study, both
the 4 mg/day and 6 mg/day doses of a monthly oxybutynin vaginal ring demonstrated
statistically significant treatment effects and similar efficacy when compared to placebo
for the primary outcome measure of reduction in the weekly number of reported
incontinence episodes in menopausal women with symptoms of predominant or pure urge
incontinence, urinary urgency and elevated urinary frequency. That such effects were
similar to the results demonstrated in the overall study population implies that the
treatment effect is maintained when considering post-menopausal women as candidates
for therapy.
Menopausal Subjects: MITT Cohort - Total Number of Incontinence Episodes: Change
from Baseline to End-of-Treatment
*Change = Change in total number of incontinence episodes from initiation of
treatment to end-of-treatment
**Difference = Difference between active treatment groups and placebo
***P-Value: Significance between active treatment groups and placebo was tested
on raw data analysis
P-33.
Vaginal estrogen therapy with promestriene in oncology patients
Lino Del Pup, Medicine. Gynecological Oncology, National Cancer Institute, Aviano,
Italy
Objective: The estradiol diether derivative, promestriene, was tested in oncology patients
suffering from severe vaginal dryness and dyspareunia because of its presumed absence
of significant absorption. Labrie (1) reported a relevant increase in serum estrone of about
500% and 150% folds with vaginal estrogens (CEE and with E2 tablets respectively). As
compared to both E1 and E2 precursors, E1S is present at 10-50 fold higher plasma
concentration that enables its more sensitive quantification with a better inter-assay
variation. Futhermore it is characterized by a prolonged half-life that makes its
measurement independent from the blood sampling time and from the problems
associated to the diurnal variations suffered by E1 and E2. The circulating pool of E1S can
thus be considered as a “reservoir” and a marker for assessing changes in women’s overall
estrogen pool during promestriene therapy. Design: 15 menopausal patients followed in
a gynecological oncology department used promestriene 10 mg soft vaginal capsules daily
for at least one month. Mean age was 51.9 years. Symptoms, vaginal pH, colposcopy
were assessed at the beginning and one month later together with estrone sulfate plasma
levels, used as a marker of overall estrogenicity and measured with very sensitive and
precise liquid chromatography-tandem mass. Results: vaginal lubrication [3 (2-4) to 5 (48)] (p= 0.008) and dyspareunia improved [3 (2-5) to 6.4 (6-8)] (p=0.007). Mean vaginal
pH decreased [5.5 (4.8-6.2) to 4.4 (4.2-5.4)] (p= 0.043). Colposcopic evaluation of atrophy
improved. Estrone sulfate plasma levels, did not change significantly [362 (22-1220) to
393 (81-856) pg/ml] (p=0.22). Conclusion: promestriene was very effective to cure
vaginal dryness and dyspareunia and to restore vaginal trophism, while plasma estrone
sulfate levels did not change significantly.
48
P-34.
Validation of the MENQOL for use with Women who have been treated
for Gynaecological Cancer or Breast Cancer
Catherine Doyle, Lauran Adams, Tracey Das Gupta, Margaret Fitch, Alison McAndrew,
Stephanie Burlein-Hall, Jennifer Blake. Sunnybrook Health Sciences Centre, Toronto,
ON, Canada
Objective: To determine if the Menopause Quality of Life (MENQOL) is a valid and
reliable instrument for use in a population of women whose menopause is a consequence
of treatment for gynaecological or breast cancer. Validation will allow the use of this tool
to measure the effect of menopause on the quality of life of these women. Design: This
is a psychometric evaluation of the MENQOL. To determine face validity, a purposively
selected sample of 10 women who met the inclusion criteria reviewed the MENQOL in
order to assess how well it measures quality of life after cancer treatment. To determine
content validity, a purposively selected group of ten experts in gynaecological or breast
cancer, menopause or quality of life reviewed the MENQOL for omissions and
appropriateness. To determine reliability and construct validity, a cross-sectional
convenience sample of 80 women who met the eligibility criteria completed:
Demographic items, MENQOL, EORTC-30, SVQ-Extended Version, and a Visual Analog
Scale for Hot Flashes. The same women completed the MENQOL and the Visual Analog
Scale for Hot Flashes two weeks later Results: Women with a confirmed diagnosis of
breast or gynaecological cancer who experienced menopause as a result of their cancer
treatment were asked to participate in this study. Women who were taking hormone
replacement therapy were excluded. Accrual for this study is ongoing. This abstract will
report the characteristics of the first 54 participants. We anticipate accrual will be
completed by July 2011. The women’s ages ranged from 29 to 58 with a mean of 47 years.
81% reported a breast cancer diagnosis; 19% were diagnosed with a gynaecological
cancer. 78% of the women were married or in a common law relationship and 72%
reported completing college or university. The items on the MENQOL that had the highest
number of ‘yes’ responses included those items measuring vasomotor symptoms. 85% of
women reported experiencing hot flashes; 75% reported night sweats and 79% reported
sweating. 83% of women reported feeling tired or worn out and 83% of women reported
trouble sleeping. 75% of women reported feeling a lack of energy. Mean scores for
symptoms indicate the level of bothersome. Participants indicated on scale of 0 (not at all
bothered) to 6 (extremely bothered) for each symptom. Reported are mean and standard
deviation for each symptom. Vasomotor symptoms were among the highest, including
hot flashes 4.07(1.68), night sweats 3.88(1.86); and sweating 4.00 (1.65). Weight gain
was the item that women were most bothered by, with a mean score of 4.62(1.79). Other
items that women ranked as bothersome were the items measuring sexual and intimacy
changes including change in sexual desire 4.24(1.99); vaginal dryness during intercourse
4.20 (1.98), and avoiding intimacy 4.12(2.09). Feeling tired or worn out also scored high
at 4.02(1.59). Conclusion: The consequences of cancer treatment, including menopause,
has a significant effect on the quality of life for women diagnosed with breast or
gynaecological cancer. In particular, women were bothered by vasomotor symptoms,
changes in sexuality and vaginal dryness. The high incidence and interrelationship of
night sweats, feeling tired, difficulty sleeping, and a lack of energy, in conjunction with
how high women rank these items in terms of affecting their quality of life may provide
a focus for directing interventions at this group of cancer survivors.
P-35.
There is a Sustained Decrease in Pap Smear and HPV Concordance with
Increasing Age: When Should we Stop Screening the Low Risk
Perimenopausal Patient?
Cindy M. Duke, BS, MS, MD, PhD1, Wen Shen, M.D.1, Kathryn Chang2, Michelle Silver2,
Raphael Viscidi4, Anne Burke1, Patti E. Gravitt2,3. 1Department of Gynecology &
Obstetrics, Johns Hopkins Medical Institutions, Baltimore, MD; 2Department of
Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD;
3
Department of Molecular Microbiology & Immunology, Johns Hopkins Bloomberg
School of Public Health, Baltimore, MD; 4Department of Pediatrics, Johns Hopkins
Medical Institutions, Baltimore, MD
Objective: The majority of women participating in cervical cancer screening programs
in the United States today are over age 35 and have generally been well screened in the
past. Despite their low risk (and no new risk factors) many women and their providers are
reluctant to deviate from the tradition of ‘Annual Pap Smears’. Current pap testing
guidelines for the perimenopausal woman, even when she is low risk, recommend
screening every three years after a documented history of three consecutively negative
paps and reflex human papillomavirus (HPV) testing if abnormal cytology on pap screen.
We conducted a study to evaluate HPV and cytological abnormalities in a population of
perimenopausal women (age 35-60) attending routine screening at gynecologic clinics to
assess the concordance between ASCUS (or worse) pap and high risk HPV (HR-HPV)
prevalence to determine whether current practice guidelines, as they relate to the
perimenopausal woman, should be revised. Design: A prospective cohort of women age
35-60 years who received routine care at one of four primary Baltimore, Maryland GYN
clinics was enrolled according to institutional IRB guidelines. Participants were seen at
semi-annual clinic visits from 2008 to 2011. Exclusion criteria included previous
hysterectomy, current pregnancy, history of organ transplant or HIV infection, unwilling
to provide contact information, non-English speaking, or inability to provide informed
consent. Demographic data including socioeconomic status, menstrual history,
reproductive history, past pap history, use of exogenous hormones, sexual history, smoking
and alcohol use were collected. HPV genotyping was performed using Roche Linear
Array VLP serology for HR-HPV and pap smear data including reflex HPV testing was
retrieved from the medical record. After adjusting for age, race, education, marital status
and clinic, statistical analyses were performed using chi squared analysis. Results: A
NAMS11_Regular-LB_Abstracts-2 8/29/11 4:13 PM Page 18
total of 882 women were enrolled. The majority of study participants have a college
degree. Median household income was $80,000-$100,000. Approximately 70% of
participants were white and approximately 20% were black. 46.7% reported having an
abnormal pap in the past, and in over half of these women, the last abnormal pap was
over 10 years ago. Only 6.0% reported having an abnormal pap within the last year. 18.7%
of women reported having had treatment for abnormal pap in the past (laser, cryotherapy,
cone or leep). At baseline, 9.0% of women tested positive for HR-HPV and 18.8% tested
positive for any HPV. The prevalence of any pap abnormality >= ASCUS was 4.7%. Of
these, 62.5% were ASCUS, 5% were ASC-H, and 32.5% were LSIL. The overall
concordance between HR-HPV positivity and pap abnormality was 89.9% (p<0.001) with
a low positive concordance of 13.9%. The ratio of HR-HPV positive to normal pap
discordant results were significantly more common than the ratio of HR-HPV negative to
abnormal pap results (test for symmetry p=0.0002). Seven out of twenty-six women with
a HR-HPV negative abnormal pap result (26.9%) had low risk HPV infection, but the
majority of pap+/HR-HPV negative results were completely negative for HPV. The
concordance of pap abnormality and HR-HPV status among women positive by either or
both methods declined with increasing age: age 35-39 =22.6%, age 40-44 =16.0%, age
45-49 =8.0%, age 50-54 =6.3%, age 55-60 = 0% (all HR-HPV positive patients in this age
group had a normal pap). Conclusion: In a population of 882 women participating in
routine pap screening, no high-grade disease was detected suggesting that perimenopausal
women with a history of negative cervical cancer screening are at low risk for developing
cervical cancer. The relatively high prevalence of HR-HPV and the declining concordance
between pap and HPV test results with increasing age suggests a re-evaluation of the
meaning and risk of positive screening test results in well-screened perimenopausal
women is needed.
Society to questions about their use of compounded and off-label hormone therapy.
Design: A brief survey was distributed to all attendees of the 2010 Annual Meeting of The
North American Menopause Society at the time of registration. In addition to age and
gender, the questions included the following: Do you ever prescribe compounded hormone
products? If no, do you prescribe FDA-approved testosterone products off-label for
women? Please indicate which compounded hormones you prescribe: estradiol, estrone,
estriol, progesterone, testosterone, DHEA. Does your compounding pharmacist include
a list of hormone risks and benefits for the patient? What percentage of your hormone
prescriptions is compounded? Do you personally use compounded hormones? Results:
Of 1,299 attendees, 576 were clinicians; 318 attendees (235 of whom were female)
completed the survey (24% of the total in attendance, 55% of clinicians). Among the
respondents, 69% indicated they had prescribed compounded hormones. Among those
who answered no (91), 45% indicated they had prescribed FDA-approved testosterone
off label for women. Testosterone was the most frequently compounded hormone. 53%
were not sure if their compounding pharmacist provided product information
(risks/benefits) to the patient; 15% indicated the pharmacist did not. More than 1/3
(n=135) reported compounding represented 10% or more of their prescriptions. Only 8%
personally used compounded hormones. Sixty-five comments provided by respondents
indicated compounding is an important issue in their practice: “Only prescribe for patients
who insist or come to me already on them.” “Please have FDA approve testosterone
transdermal for women!” “For HT, only for patients that really push for this.” “ I will be
very interested in these results.” “ I look forward to not needing to use compounded
anything!” Conclusion: The results of this survey indicate that among clinicians seeing
menopausal women, compounding hormones is a significant issue. More data are required
to determine the extent of this practice, the need that it fills, and the efficacy, safety and
financial impact in our society.
P-36.
Escitalopram Treatment of Menopausal Hot Flashes
Robert R. Freedman, Ph.D.1,2, Michael L. Kruger, M.S.2, Manuel E. Tancer, M.D.1.
1
Psychiatry, Wayne State University School of Medicine, Detroit, MI; 2Obstetrics and
Gynecology, Wayne State University School of Medicine, Detroit, MI
Objective: To determine the effects of 10 mg and 20 mg/day of escitalopram on
objectively-recorded hot flashes (HFs) and on the rectal temperature threshold for
sweating. Design: Two studies were performed: 16 women received 10 mg/day and 26
women received 20 mg/day escitalopram in double-blind fashion for eight weeks. They
were required to report at least six HFs/day, be in the age range of 44-59 years, be free of
any antidepressant drugs, hot flash treatment drugs or supplements (soy, herbs), have BMI
under 32, and be nondepressed as determined by Dr. Tancer using the M.I.N.I.
International Neuropsychiatric Interview, a short, structured, psychiatric interview. The
rectal temperature threshold for sweating was measured in the laboratory, using published
methods, during the first and eighth weeks of the investigation. HFs were physiologically
measured by a miniature, ambulatory recorder for the first three weeks and the eighth
week of the study. Data from the preliminary study were analyzed using a 2-way, repeatedmeasures, analysis of variance. Data from the second study were analyzed with a 2-way
(Group x Time), repeated-measures, analysis of covariance using BMI as a covariate. To
control for differences in HF frequency at baseline (week 1), data from subsequent weeks
were expressed as percentages of the week one data. Results: For the first study, there
were no significant effects whatsoever for any measure. The results for the second study
are shown in the table below. There were no significant differences between the two
groups for hot flash frequency or for rectal temperature sweating threshold at any time
point. Conclusion: At 10 mg or 20 mg/day, escitalopram is not effective in the treatment
of menopausal HFs. (Supported by AG-05233 from NIH)
Hot Flash Frequencies by Week as Percent of Baseline Adjusted for BMI
P-37.
Results from 2010 NAMS Survey on use of Compounded and Off-label
Hormone Products
Margery Gass, MD1,2, Cynthia Stuenkel, MD3. 1The North American Menopause Society,
Mayfield Heights, OH; 2Cleveland Clinic, Cleveland, OH; 3University of California San
Diego, San Diego, CA
Objective: There are no published data on the extent to which compounded hormone
therapy is being used in the United States. Prescriptions for hormone therapy approved by
the Food and Drug Administration are tracked and reported intermittently, but
compounded prescriptions are not tracked on a national level. This report reflects the
responses of attendees at the 2010 Annual Meeting of The North American Menopause
Number prescribing DHEA, E1, E3, E2, P4, and Testosterone.
P-38.
The hopeless age?: An exploration of the experience of menopause in Arab
women living in Qatar
Madhuvanti Murphy, Dr.P.H.1, Mohamud A. Verjee, MBChB2, Linda M. Gerber, Ph.D.1.
1
Public Health, Weill Cornell Medical College, New York, NY; 2Weill Cornell Medical
College in Qatar, Doha, Qatar
Objective: Given that there is no published literature to date on how Qatari women
conceptualize and experience menopause, this research aimed to qualitatively describe
and examine the expectations and experiences of the midlife transition in Arab women
living in Qatar. Design: This qualitative research was the first phase of a larger mixedmethod study modeled after the SWAN study. Six focus groups of approximately 7
women each were conducted with Arab women living in Qatar; 3 groups were made up
of local Qatari women only, and the other 3 groups with non-Qatari Arab women
originating from neighboring countries. A purposive sample of 41 pre-, peri-, and postmenopausal women aged 40 to 60 participated. The semi-structured group format
encouraged discussion around knowledge about menopause; physical, emotional and
social experiences related to menopause; and, opinions on cultural differences that may
exist related to menopause. Focus groups were audio-taped and conducted in Arabic, and
were later translated into English. Transcripts were imported into Atlas.ti software and
examined for the creation of codes and emerging themes. Comparisons were conducted
between Qatari and non-Qatari groups. Information from the groups was used to inform
the development of the survey for the quantitative phase of the study. Approval was
received from the Institutional Review Boards of Weill Cornell Medical College-Qatar and
the Hamad Medical Corporation, Qatar. Results: The majority of women (Qatari and
non-Qatari) considered menopause a maturing experience, but preferred not to use the
term ‘menopause” as it translates as “hopeless age” in Arabic, which was considered to
have negative connotations. Post-menopausal women described menopausal symptoms
consistent with general knowledge, such as hot flashes, tiredness and mood swings, but
many pre-menopausal women were unaware of the symptoms associated with menopause,
even if they knew someone who had experienced menopause. Women acknowledged that
the experience of menopause affected their relationships with their children and husbands,
particularly the mood swings, as they would become very emotional. Some women had
been recommended hormone replacement therapy by their doctors in order to continue
having their periods, but many refused as they did not want more children. Diseases such
as osteoporosis and vitamin D deficiency were considered linked to menopause. Postmenopausal women were more socially active than before, and were thankful to be able
49
Clinical Poster Presentations (continued)
to travel, spend more time with their families and friends, and participate in religious
activities that they previously could not attend during menses. The role of the husband was
a very important theme as how a woman experienced menopause depended on the
husband’s level of support. Many women initially did not tell their husbands they were
menopausal fearing they would marry younger wives, and some believed that menopause
was brought on by disputes with husbands. Some women also believed that Western
women did not have the appropriate support from husbands and families that Arab women
have during menopause, and felt this lack of support could lead to negative outcomes
such as being at an increased risk for suicide caused by depression during menopause.
Conclusion: Qatari and non-Qatari women have many similarities in how they perceived
and experienced menopause, although they collectively believe the experiences of Western
women are different. The fact that menopause allowed ladies to devote more time to
religion, which plays an important part in daily life activities in Qatar, seems to be one of
the reasons why this period is looked upon favorably. When developing instrumentation
for future women’s health-related research in this culture, researchers need to take into
consideration questions on spousal and familial influence in order to be culturally
appropriate.
P-39.
Anxiety and Depressive Symptoms Following Natural Menopause,
Hysterectomy with Ovarian Conservation, and Hysterectomy with
Bilateral Oophorectomy
Carolyn Gibson, MPH, MS1, Hadine Joffe, MD, MSc2, Joyce Bromberger1, Rebecca C.
Thurston, PhD1, Tené Lewis3, Naila Khalil4, Karen Matthews1. 1University of Pittsburgh,
Pittsburgh, PA; 2Massachussetts General Hospital, Harvard Medical School, Boston, MA;
3
Yale University School of Medicine, New Haven, CT; 4Wright State University, Dayton,
OH
Objective: Cross-sectional studies suggest an association between negative affect and
hysterectomy, but whether negative mood states may be a result of hysterectomy and/or
oophorectomy is unclear. We used prospective data to examine mood trajectories in the
years prior to and following natural menopause, hysterectomy with ovarian conservation,
and bilateral oophorectomy among women in midlife. Design: Data were from the Study
of Women’s Health Across the Nation (SWAN), a multi-site community-based prospective
cohort study of the menopausal transition (n=1,997). Depressive and anxiety symptoms
were assessed at each of up to 11 annual visits with the Center for Epidemiological Studies
Depression Index (CES-D) and four questions about anxiety symptoms. Piecewise
hierarchical linear growth models were used to relate natural menopause, hysterectomy
with ovarian conservation, and hysterectomy with bilateral oophorectomy to linear growth
trajectories of depressive and anxiety symptoms before and after the final menstrual period
(FMP) or surgery. Covariates included body mass index, self-rated health, hormone
therapy, and antidepressant use, reported at each visit; educational attainment and
race/ethnicity, assessed at baseline; menopausal status the year prior to FMP or surgery;
and age at the time of FMP or surgery. Results: Between annual visits 1-10, 1,816 (90.9%)
of participants reached natural menopause, 78 (3.9%) reported hysterectomy with ovarian
conservation for benign conditions, and 103 (5.2%) reported hysterectomy with bilateral
oophorectomy for benign conditions. For all women, depressive symptoms decreased in
the years leading up to (B= -.13, p<.001) and following (B = -.21, p<.001) FMP or surgery.
Anxiety symptoms decreased in the years following FMP or surgery (B = -.05, p<.001).
These trajectories did not significantly differ by hysterectomy or oophorectomy status.
Additional factors related to higher depressive symptoms were poorer self-rated health (B
= 1.65, p<.001) and antidepressant use (B = 1.87, p<.001), while depressive symptoms
were lower with hormone therapy use (B = -.38, p=.03) and advanced educational
attainment (B = -1.74, p<.001). Anxiety symptoms were higher with antidepressant use
(B = .41, p<.001) and poorer self-rated health (B = .36, p<.001), and lower with hormone
use (B = -.09, p=.04) and among African American (B = -.27, p=.01) and Chinese (B = .41, p=.02) women. Conclusion: In this prospective examination, mood symptoms
improved before and after the final menstrual period. Trajectories of mood symptoms
before and after hysterectomy, with or without ovarian conservation, were not significantly
different than those of naturally menopausal women before and after their final menstrual
period. The Study of Women’s Health Across the Nation (SWAN) has grant support from
the National Institutes of Health (NIH), DHHS, through the National Institute on Aging
(NIA), the National Institute of Nursing Research (NINR) and the NIH Office of Research
on Women’s Health (ORWH) (Grants NR004061; AG012505, AG012535, AG012531,
AG012539, AG012546, AG012553, AG012554, AG012495). The content of this abstract
is solely the responsibility of the authors and does not necessarily represent the official
views of the NIA, NINR, ORWH or the NIH.
P-40.
Baseline and Seasaonal Variation in the Serum Levels of Vitamin D in
Postmenopausal Women. Relationship With Cardiovascular and Bone
Metabolic Markers
Miguel Gonzalez-Izquierdo1, Sílvia Tamarit Bordes1, Aitana Monllor Tormos1, Marta
Ferrer Piquer1, Lorena Sabonet Morente1, Maria An García Pérez2, Antonio Cano1,3.
1
Obstetrics and Gynecology, Hospital Dr Peset, Valencia, Spain; 2Research Foundation,
Hospital Clinico, Valencia, Spain; 3Obstetrics and Gynecology, University of Valencia,
Valencia, Spain
Objective: To measure the circulating levels and the seasonal variation of 25 (OH)
vitamin D in a population of healthy postmenopausal women living in a Mediterranean
area. To disclose any relationship between 25(OH) D levels and cardiovascular parameters
or bone metabolic markers Design: We recruited 133 postmenopausal women, determined
their value of 25 (OH) vitamin D in serum (Roche electrochemiluminescence system,
Elecsys 2010, Roche Diagnostics, GmbH, Mannheim, Germany), and collected data about
50
their cardiovascular and bone metabolic markers. Serum levels of carboxyterminal
telopeptide of type 1 collagen (beta-crosslaps, B-CTX, electrochemiluminescence Elecsys
2010, Roche Diagnostics, GmbH, Mannheim, Germany) were used as indicators of bone
resorption. Serum levels of total alkaline phosphatase, creatinine, phosphate, total calcium,
magnesium, cholesterol, triglycerides, and glucose were determined with the use of an
autoanalyzer Olympus AV 5200, Tokyo, Japan). Insulin and parathyroid hormone (PTH)
were measured by conventional immunoradiometry Results: The mean age of women
was 57.9 years. The average age of menopause was 46.3 years. The mean baseline vitamin
D was 23.3ng/ml. We analyzed the relationship of serum vitamin D levels with type of
menopause (natural/surgical), and with the above mentioned cardiovascular and bone
metabolism parameters. We found only a trend, although not significant (p=0.054), of
negative correlation between PTH values and 25(OH) D. Of the total 133 women, we
measured 25(OH) D values of 38 in winter, with a mean value of 23,1ng/ml; of 40 in
spring with a mean of 21,9ng/ml; of 20 in summer with a mean of 26,7ng/ml; and of 35
in autumn with a mean of 23,1ng/ml. Despite the slight increase in summer no statistical
differences were found between the seasonal groups Conclusion: In this Mediterranean
area we found a high prevalence of inadequate levels of vitamin D, and this was not
substantially modified by the season of the year. There was a trend of negative correlation
between 25(OH)D and PTH. We could not detect any significant relationship between
cardiovascular or bone metabolic markers and the serum levels of 25(OH)
P-41.
Effects of Supplmentation With 25-OH-D3 (Calcifediol), A Vitamin D
Analogue, On The Serum Levels of Vitamin D in Postmenopausal Women
Miguel Gonzalez-Izquierdo1, Sílvia Tamarit Bordes1, Aitana Monllor Tormos1, Maria
Tarrazó Millet1, Aitana Gisbert Vicent1, Maria An García Pérez2, Antonio Cano1,3.
1
Obstetrics and Gynecology, Hospital Dr Peset, Valencia, Spain; 2Reserch Foundation,
Hospital Clínico Universitari, Valencia, Spain; 3Department of Pediatrics, Obstetrics and
Gynecology, University of Valencia, Valencia, Spain
Objective: To describe the change in the levels of vitamin D after calcifediol, a vitamin
D analogue, and the effects on serum parameters of bone metabolism in a group of
community-based healthy postmenopausal women Design: We recruited 260
postmenopausal women, determined their value of 25(OH) D in blood (Roche
electrochemiluminescence system, Elecsys 2010, Roche Diagnostics, GmbH, Mannheim,
Germany), and collected data about bone metabolic markers. Serum levels of
carboxyterminal telopeptide of type 1 collagen (beta-crosslaps, B-CTX,
electrochemiluminescence Elecsys 2010, Roche Diagnostics, GmbH, Mannheim,
Germany) were used as indicators of bone resorption. Serum levels of total alkaline
phosphatase (U/L), creatinine (mg/dl), phosphate (mg/dl), total calcium (mg/dl), and
magnesium (mg/dl) were determined with the use of an autoanalyzer Olympus AV 5200,
Tokyo, Japan). The circulating concentration of parathyroid hormone (PTH, pg/ml) was
measured by immunoradiometry (DiaSorin, Stillwater, USA). Forty seven women were
supplemented with calcifediol (15000 IU every two weeks). Both treated and untreated
women were investigated after 6 months Results: The mean age of the women was 57.9
years and the average menopausal age was 46.3 years. The mean baseline level of 25(OH)
D was 23.3ng/ml. The mean baseline level of 25(OH)D in the supplemented group was
20,1ng/ml, and increased significantly to a mean value of 40,4ng/ml after 6 months. There
was a considerable variation in the circulating levels achieved by each woman. In the
non-supplemented women, the mean baseline 25(OH)D value of 25.1ng/ml remained
unchanged (25.7ng/ml) at the 6th month. The supplementation with calcifediol was
associated with a 2 % increase in the the calcemia, from 9.8mg/dl to 10mg/dl, with a
stadistical signification, and a decrease in PTH levels from 55,8pg/ml to 50,5pg/ml
without stadistical signification. We could not detect any other biochemical change in the
remainder of the bone parameters that were assessed Conclusion: In this Mediterranean
area we found a high prevalence of inadequate levels of vitamin D. Supplementation with
calcifediol achieved mean levels of 25(OH)D, which exceeded the recommended
threshold of 30 ng/ml. This change was associated with a slight increase in the level of
serum calcium, but PTH serum levels did not modify significantly
P-42.
Etiological profile of women presenting with premature ovarian failure
in Sultan Qaboos University hospital, Sultanate of Oman
Vaidyanathan Gowri1, Jayakumar D. Dennison, MD2, Anil V. Pathare2. 1obstetrics and
gynecology, Sultan Qaboos University, Muscat, Oman; 2Haematology, Sultan Qaboos
University, Muscat, Oman
Objective: study the etiological factors of women presenting with premature ovarian
failure and their hormonal profile in Sultan Qaboos university hospital Sultanate of Oman
Design: A retrospective study from electronic patient records form Jan 1998- Dec 2010
Results: There were a total of 53 patients during the study period. 40 of them were
following bone marrow transplant BMT) treatment for hematological disorders and the
remaining 13 presented with either amenorrhea or infertility. Of the 13 patients, three
patients had other endocrine disorders like hypothyriodism and or diabetes and one had
a chromosomal abnormality of deletion (46Xdel (x) q24-25, interstitial deletion). The
mean age of the patients at the time of menopause who did not have bone marrow
transplant was 35.8 years, mean Follicle stimulating hormone was 63IU, Luteinizing
hormone was 30 IU, prolactin was173 IU and Thyroid stimulating hormone was 2.35 IU.
In women/girls who received bone marrow transplant for various reasons including acute
and chronic leukemia, Thalasemia, Sickle cell disease and Paroxysmal nocturnal
hemoglobinuria the age range was from 4 years to 40 years. The mean Follicle stimulating
hormone, Luteinizing hormone and Thyroid stimulating hormone in the BMT group is
shown below in a table. There was no significant difference in the hormonal profile though
the age of onset was significantly different between the groups by Mann- Whitney test (
NAMS11_Regular-LB_Abstracts-2 8/29/11 4:13 PM Page 20
p value =0.000) Girls who received bone marrow transplant after 2010 with Reduced
intensity conditioning regimen (RIC) resumed periods and one of them even got pregnant
Conclusion: The most common etiology of premature ovarian failure in this study was
following BMT for hematological disorders. Recent changes like RIC therapy might help
to avoid this problem and preserve ovarian function
FSH- Follicle stimulating Hormone
LH- Luteinizing hormone
TSH- thyroid stimulating hormone
P-43.
Patterns of Brain Activation and the Neural Effects of Objective Hot
Flashes in Highly Symptomatic Postmenopausal Women
Rhoda Jamadar1, Deborah M. Little4, Leah H. Rubin1, Deanne Fornelli1, Lauren L.
Drogos, M.A.2, Stacie Geller3, Lee P. Shulman5,6, Suzanne Banuvar5, Pauline M. Maki1,2.
1
Department of Psychiatry, University of Illinois at Chicago, Chicago, IL; 2Department of
Psychology, University of Illinois at Chicago, Chicago, IL; 3Department of Obstetrics
and Gynecology, University of Illinois at Chicago, Chicago, IL; 4Department of
Neurology, University of Illinois at Chicago, Chicago, IL; 5Northwestern University,
Chicago, IL; 6Northwestern Memorial Hospital, Chicago, IL
Objective: Functional neuroimaging studies provide insight into the cognitive processes
and brain areas influenced by the menopausal transition. We previously reported that
verbal memory performance on a paragraph recall test was negatively associated with
objective hot flashes (HF) as measured by an ambulatory skin conductance monitor in
midlife women with moderate to severe hot flashes. In contrast, subjective hot flashes
were unrelated to memory. In the present study we used functional magnetic resonance
imaging (fMRI) to investigate brain circuitry during a verbal memory task in midlife
women and in relation to objective and subjective hot flashes. Design: Fourteen
postmenopausal women (mean age= 54, 64% African-American) with moderate to severe
vasomotor symptoms (>35 HF/week) completed fMRI assessments of verbal memory. A
delayed recognition memory task requiring encoding and recognition of novel
(experimental) and frequently repeated (control) words was used. A subset of 9 women
wore an ambulatory sternal skin conductance monitor for 24 hours. Objective and
subjective (button press) HF were recorded. Participants also completed a neurocognitive
battery including verbal memory measures outside the scanner including paragraph recall.
Imaging data were pre-processed and analyzed using Statistical Parametric Mapping
(SPM5). A whole brain voxel-wise analysis was used to identify brain regions activated
during encoding and recognition (novel words minus repeated words). A priori regions of
interest included the hippocampus and prefrontal cortex (PFC). In the subset of 9 women
with hot flash data, we related objective and subjective hot flashes to patterns of brain
activation. Results: Significant regions of activation during the encoding condition
included bilateral prefrontal cortex (PFC), right ventral lateral prefrontal cortex (vlPFC),
right thalamus, right amygdala and left hippocampus. Significant regions of activation
during recognition included bilateral PFC, left vlPFC, bilateral dorsal lateral prefrontal
cortex (dlPFC) and posterior cingulate cortex (PCC). Participants subjectively reported
60% of objective hot flashes. On the neurocognitive battery, objective (but not subjective)
hot flashes correlated significantly with delayed paragraph recall scores (r= -.697 p<.05).
During the experimental (novel words) minus control (repeated words) condition of the
encoding task, objective hot flashes were negatively correlated (p<.01) with activation in
the dlPFC and orbitofrontal cortex. There were no correlation between subjective hot
flashes and activation during encoding of experimental minus control conditions.
Conclusion: To our knowledge, this is the first neuroimaging study of objective hot
flashes in relation to brain activation patterns during a cognitive task. Consistent with
previous studies in asymptomatic women, symptomatic postmenopausal women show
activation in a neural network that included PFC, hippocampus, and cingulate cortex. We
are the first to report that objectively measured hot flashes are negatively correlated with
the PFC during performance of a cognitive task. Notably, activity decreased in women
with more objective hot flashes during effortful memory processing (experimental minus
novel conditions). Subjective hot flashes did not relate to activation in this network.
Combined with our previous report that objective but not subjective hot flashes predict
verbal memory declines, this fMRI study underscores the importance of measuring
physiological hot flashes in relation to cognitive function.
P-44.
Menopausal Medicine Clinic: An Innovative Approach to Enhancing the
Effectiveness of Medical Education
Xuezhi Jiang, MD1, Shiv Sab1, Peter F. Schnatz, D.O.1,2. 1ObGyn&Internal Medicine, The
Reading Hospital and Medical Center, Reading, PA; 2ObGyn&Internal Medicine,
Jefferson Medical College of Thomas Jefferson University, Philadelphia, PA
Objective: Despite a large number of menopausal women in the United States, education
in this area of medicine has been limited. The purpose of this study was to assess the
effectiveness, using a pre- and post-test, of a menopausal medicine clinic to enhance
trainees’ medical knowledge. Design: This study was performed at Hartford Hospital
(HH) under the oversight of the HH IRB. Between July 2004 and May 2007, seventy
three resident physicians completed a rotation which included attending a once a week
menopause clinic. At their first visit, and before the clinic began, they were each given a
pre-test. At the end of the rotation, a post-test was given that was different from the pretest (Test A was sometimes given first and Test B was sometimes given first). Each test
contained questions on topics covering menopause, perimenopause, and general women’s
health (important for menopause clinicians to know but not specific to menopause). At the
end of each testing session, each resident was given a total score (evaluating menopause
and non-menopause related questions) and a menopause score (pertaining to menopause
related questions only). Results of the post-test were compared to the pre-test in order to
determine the efficacy of the clinic in educating the participants on menopause related
issues. Results: The mean (+/- SD) pre-test menopause score and total score were 63.2%
(+/- 13.3%) and 63.7% (+/- 11.3%), respectively. The mean post-test increase in the
menopause score was 14% with a median score increase of 10.2%. The range of post-test
results went from a maximum decrease of 7.8% to a maximum increase of 47.1%
(p<.0001, figure 1). The mean increase in the total score was 13% with a median increased
of 10.7%. For the total score, the range went from -7.2% to 39.3% (p<.0001, figure 1).
There was no correlation between the score changes and the number of clinic sessions
attended, the specialties of resident training (OB/GYN vs. non OB/GYN), the level of
training (PGY1 or PGY2), or the order in which the examinations were taken (test A vs.
test B taken first). Conclusion: The number of menopausal women, and the demand for
physicians to care for them, continues to grow. Results of this study suggest that overall,
the menopause clinic successfully added to the breadth of knowledge of resident
physicians about menopause related matters. Menopause clinics may provide hope for
women, and the medical community, that creative and innovative educational programs,
such as a menopause clinic, may help educate future physicians in their ability to care for
menopausal women.
P-45.
Average concentration of endogenous sex hormones in healthy
postmenopausal women not taking hormone therapy
Roksana Karim, MBBS, PhD1, Wendy J. Mack2, Howard N. Hodis3, Chun-Ju Chien4,
Frank Z. Stanczyk5. 1Pediatrics and Preventive Medicine, University of Southern
California, Los Angeles, CA; 2Preventive Medicine, University of Southern California,
Los Angees, CA; 3Medicine, University of Southern California, Los Angees, CA;
4
Preventive Medicine, University of Southern California, Los Angees, CA; 5Obstetrics
and Gynecology, University of Southern California, Los Angees, CA
Objective: While reference ranges of sex hormone concentrations are well defined for
women of reproductive age, such ranges are not well established for postmenopausal
women. Peripheral adipose tissue serves as an important source for sex hormones in
postmenopausal women. Therefore, the reference concentrations of sex hormones in
postmenopausal women need to be controlled for obesity. Although the associations of sex
hormone concentrations with age and body mass index (BMI) are well known, the average
concentrations of endogenous sex hormones have not been identified in a reasonably large
sample of healthy postmenopausal women by age groups, controlled for BMI and type of
menopause. Design: Serum concentrations of estrone (E1), total and free estradiol (E2,
FE2, respectively), total and free testosterone (T, FT, respectively) and sex hormone
binding globulin (SHBG) were assessed in 857 healthy postmenopausal women not taking
hormone therapy. E1 and E2 concentrations were also measured in baseline samples of
another ongoing trial (n = 350). E1, E2, and T were measured by validated
extraction/chromatographic RIAs, whereas SHBG was measured by direct
chemiluminescent immunoassay. FE2 and FT levels were calculated by using a validated
algorithm. Sex hormone and SHBG levels were log transformed. Linear regression models
were used to obtain mean (SD) sex hormone concentrations for each 5-year age group
adjusted for BMI (continuous) and type of menopause (natural vs. surgical). Results: The
study participants were on average(SD) 60.4(7) years old, predominantly white (65%),
with average BMI of 27.3(5.4) kg/m2. There was a significant positive association of all
the hormones, except T, with BMI. SHBG was also significantly associated with BMI, but
51
NAMS11_Regular-LB_Abstracts-2 8/29/11 4:13 PM Page 21
Clinical Poster Presentations (continued)
inversely. T and FT levels were lower among surgically menopausal women. Average
concentrations of sex hormones by 5-year age group, adjusted for BMI and/or type of
menopause are shown in Table A. Endogenous concentrations of T and SHBG show
significant increasing trend with increasing age. Conclusion: We report BMI-adjusted
average concentrations of sex hormones and SHBG by age group in healthy
postmenopausal women, which can be used for reference values in research studies as
well as in clinical practice.
Table A: Levels of sex hormones and SHBG by age, adjusted for BMI
indicated. For post menopausal women who demonstrates vulvovaginal and clitoral
atrophic changes, including architectural changes and phymosis, topical compounded
testosterone cream may be added for incremental benefit. Phase 3: a) Identify medications
that may negatively impact sexual orgasmic response, and attempt to change, decrease or
alter dose. If selective serotonin reuptake inhibitor (SSRI) is the offending agent, patients
(or health care professionals) should consider adding a dopamine agonist to the SSRI
regimen or changing to a new antidepressant. Women can also consider adding a
phosphodiesterase inhibitor “antidote” precoitally. b) Phosphodiesterase Inhibitors
(PDE5I) Agents: Medications like phosphodiesterase inhibitors may prove to be helpful
for SSRI induced orgasmic changes as well as for selected women who have orgasmic
changes. Compounded PDE5I applied to clitoral tissues or 25-50 mg of oral Sildenafil 4060 minutes prior to intercourse might result in improved sexual response. Results:
Presented is a treatment paradigm to help ameliorate the issues related to postmenopausal
changes in orgasmic latency and frequency. The paradigm shifts from minimally invasive
to more systemic therapeutic options, which can minimize potential side effects. This
model has proven beneficial in over 75 postmenopausal women in two large busy sexual
medicine practices on two coasts of the USA. Conclusion: Female Orgasmic Disorder is
complex and multifaceted in the cancer survivor and further research is needed to confirm
its utility of proposed paradigms in large scale populations.
P-48.
The change of the 8-hydroxydeoxyguanosine concentrations according to
hormone therapy and association with Ser326Cys polymorphism of
OGG1 gene in postmenopausal women receiving hormone therapy
*Adjusted for BMI
** Adjusted for type of menopause
*** Adjusted for BMI and type of menopause
P-46.
Comparison of the Effects of Hormone Replacement Therapy on Bone
Mineral Density, Lipid Profiles, and Biochemical Markers of Bone
Metabolism in postmenopausal women
JangHeub Kim, Jeong Namkung, Young-Ok Lew, Mee-ran Kim. The Catholic University,
Seoul, Republic of Korea
Objective: Objective: To assess the effects of hormone replacement therapy on bone
mineral density (BMD), biochemical markers of bone turnover, and lipid profiles in
postmenopausal women. Design: Methods: We retrospectively reviewed the medical
records of 199 postmenopausal women who had received care at the Department of
Obstetrics and Gynecology of Catholic University Seoul St. Mary’s Hospital between
January 1994 and December 2008. The patients were divided into the following three
groups: group 1 received combined estrogen and progesterone therapy (n=91); group 2
received estrogen only (n=65); and group 3 received tibolone (n=43). We compared the
changes in biochemical markers of bone turnover, lipid profiles, and BMD during therapy.
Results: Results: The BMD of the lumbar spine increased in groups 1 and 3 by 2.0% and
1.2%, respectively, and the BMD of the total femur increased in groups 1 and 2 by 2.3%
and 0.5% from the initial values after 3 years, respectively. However, the BMD of the
femoral neck and total femur decreased significantly in group 3 by 4.8% and 1.9%,
respectively, 3 years after treatment initiation (p<0.05). Serum osteocalcin and urinary
deoxypyridinoline decreased in all groups 1 year after treatment. In groups 1 and 3, the
total cholesterol level decreased and the triglycerides level increased. However, there were
no definite changes in the total cholesterol and triglycerides levels in group 2. The HDLcholesterol level increased in groups 1 and 2, but decreased in group 3. As a result, the
BMD of the lumbar spine increased and the total cholesterol level decreased in the
combined therapy and tibolone groups. Tibolone had no beneficial effect on the BMD of
the femoral neck. Conclusion: Conclusions: Our results suggest that each therapy has
different effects on BMD, biochemical markers of bone metabolism, and lipid profiles. A
prospective study involving a larger group, and considering multiple factors, will be
required to obtain more clinically meaningful conclusions.
P-47.
Treatment Protocol for Postmenopausal Orgasmic Changes
Michael Krychman1,2, Susan Kellogg3. 1Southern California Center for Sexual Health,
Newport Beach, CA; 2Obstetetrics and Gynecology, University of Southern California,
Los Angeles, CA; 3Obstetetrics and Gynecology, Drexel University, Philedelphia, PA
Objective: Orgasmic complaints are common for postmenopausal women who present
with orgasmic changes in latency and frequency with respect to orgasmic potential. To
date no treatment paradigm exists that offers the health care provider some guidance in
order to manage these troublesome issues in women living with cancer. Design: Presented
here is a proposed paradigm for the treatment of orgasmic complaints that affect latency
and intensity of orgasm. Phase 1: a) Bibliotherapy, Sexuality Education, Self Stimulation,
Use of Vibrator/Stimulator - Begin a sexual response educational program which includes
education about anatomy and physiology of sexual response. Phase 2: a) Topical
Nutraceuticals; Products that may enhance genital sensitivity and increase sexual
satisfaction include Zestra® Essential Arousal Oils™. b) Topical Hormonal Agents.
Minimally absorbed local vaginal estrogen creams may be beneficial, if not contra-
52
Seung-Yup Ku, MD,PhD1, Hoon Kim, MD,PhD2, Seok Hyun Kim, MD,PhD1, Young Min
Choi1, Jung Gu Kim, MD,PhD1, Shin Yong Moon1. 1Department of Obstetrics and
Gynecology, Seoul National University College of Medicine, Seoul, Republic of Korea;
2
Department of Obstetrics and Gynecology, Incheon Medical Center, Incheon, Republic
of Korea
Objective: The 8-hydroxydeoxyguanosine (8-OHdG) is excised from oxidative damaged
DNA by endonuclease repair enzymes 8-oxoguanine DNA N-glycosylase gene (OGG1)
and widely used for determination of DNA damage. The present study aimed at
investigating whether estrogen may influence on the blood/urinary 8-OHdG levels and
whether the level of blood/urinary 8-OHdG is different according to OGG1 Ser326Cys
polymorphism in postmenopausal women receiving HT. Design: In 102 postmenopausal
women receiving HT, the 8-OHdG levels were measured in the blood and urine using
high performance liquid chromatography (HPLC) before HT and 3 months after HT. The
genotyping of the Ser326Cys polymorphism of the OGG1 was performed by polymerase
chain reaction (PCR) and restriction enzyme fragment length polymorphism (RFLP)
analysis. Results: Clinical characteristics and serum concentration of 8-OHdG were not
different according to OGG1 genotypes. The level of blood 8-OHdG after HT was
significantly lower compared to that before HT (P=0.003). Although blood and urinary 8OHdG concentration were not significantly influenced by OGG1 genotypes in this
population, it has been shown that post-HT blood 8-OHdG levels were lower in three
OGG1 genotypes (P=0.01). Conclusion: : These findings imply that hormone therapy
can reduce blood 8-OHdG concentrations, one of the markers of oxidative damage.
However, the level of 8-OHdG were not different according to OGG1 Ser326Cys
polymorphism in Korean postmenopausal women receiving HT. Further study is needed
to confirm this association in larger population.
Comparison of clinical characteristics and 8-OHdG concentrations among the three
genotypes of OGG1 Ser326Cys polymorphism in postmenopausal women receiving
hormone therapy (HT)
8-OHdG: 8-hydroxydeoxyguanosine, OGG1: 8-oxoguanine DNA N-glycosylase
gene
ET: estrogen therapy, BMI: body mass index
Data are mean±SD.
P value by analysis of variance (ANOVA) between the genotypes of OGG1
Ser326Cys polymorphism
P* value by repeated measures of ANOVA before and after HT
P-49.
Decreased Bone Mineral density in Patients With Invasive Cervical
Cancer
Ji Young Lee1, Min-Hyung Jung2. 1Konkuk University, Seoul, Republic of Korea;
2
KyungHee Medical Center, Seoul, Republic of Korea
Objective: In women, osteoporosis is a common chronic disease that induces spinal
compression and femoral neck fractures, resulting in life-threatening complications. It is
very important to identify risk factors in order to prevent this disorder. Bone destruction
is a well-recognized complication in a variety of neoplasms without bone metastasis.
Therefore, in the present study, we investigated the spinal bone mineral density (BMD)
in patients with cervical cancer without bone metastases. Design: We measured spinal
bone mineral densities by dual-photon absorptiometry is 119 patients with invasive uterine
cervical cancer and compared them with measurements from 135 control women.
Results: When adjusted for age and menopause duration, mean bone mineral density in
patients with uterine cervical cancer was 13.9% lower (p=.0003) and age-matched
percentiles were 9.2% lower (p=.0003) than in control women. The deficits in bone
mineral density and age-matched percentiles were confined to the uterine cervical cancer
patients in their fifties, ie, less than 5 years’ menopause duration. Conclusion: Our study
results suggest that patients with invasive cervical cancer have a lower BMD, resulting in
an increased risk of osteoporosis.
P-50.
The effects of Tribulus terrestris on sexuality in post-menopausal women
Sonia Maria Rolim R. Lima, MD, PhD1, Sóstenes Postigo, MD1, Benedito F. Reis, MD1,2,
Silvia Saito, MD1, Sheldom R. Botogoski, PhD3, Camila P. Martins1, Guazzelli Renata1,
Tsutomu Aoki, PhD1. 1Obstetrics and Gynaecology, FCMSCSP, São Paulo, Brazil;
2
Obstetrics and Gynaecology, UNIVÁS, Pouso Alegre, Brazil; 3Obstetrics and
Gynaecology, UFPR, Curitiba, Brazil
Objective: To study the effects of Tribulus terrestris on sexuality in post-menopausal
women. Design: A prospective, randomized, placebo-controlled, double-blind trial
involving 60 post-menopausal women with sexual dysfunction was carried out. Study
participants were split into two groups: Group I (control) n = 30, and Group II (Tribulus)
n= 30. Both groups were assessed for three months based on two questionnaires: the
Inventory of Sexual Satisfaction – Female Version (GRISS), and the Female Intervention
Efficacy Index (FIEI). Statistical analyses were performed using Student’s t test, the Chisquared test with Yates correction, and the Mann-Whitney test. Results: No significant
difference was found between Groups for age, age at menopause, or time elapsed since
menopause. Results on the GRISS questionnaire showed a significant improvement in
global scores in Group II compared to Group I (p<0.001). A significant improvement on
the GRISS domains of Infrequency, Non-communication, Female sexual avoidance,
Female non-sensuality, Vaginismus and Anorgasmia, was seen in Group II compared to
Group I (p<0.05). No significant improvement in the Female dissatisfaction domain (p=
0.845) was found. Results on the FIEI questionnaire (post-treatment) revealed a significant
improvement (p<0.001) in vaginal lubrication during intercourse and/or foreplay: Group
I (20%) versus Group II (83.3%); improvement in genital sensation during sexual
intercourse or other stimuli: Group I (16.7%) versus Group II (76.7%); improvement in
sensation in the genital region: Group I (20%) versus Group II (70%); improvement in
sexual relations and/or other sexual stimulation: Group I (13.3% pleasant, 56.7%
unpleasant and 30% indifferent) versus Group II (43.3% pleasant, 16.7% unpleasant and
40% indifferent)(p=0.003); ability to reach organism: Group I (20% improved and 80%
indifferent) versus Group II (73.3% improved and 26.7% indifferent) (p<0.001). In Group
I, 20% of women reported improvement in their sexual experience and wished to continue
taking the medication, 23.3% noted no change in their sexual experience but wished to
continue taking the medication, while 56.7% stated their sexual experience was unchanged
and did not wish to continue taking the medicine. In Group II, 80% reported improvement
in their sexual experience and wished to continue taking the medication, 10% noted no
change but wished to continue taking the medication, while 10% reported no change and
did not wish to remain in use of the medication (p<0.001). In terms of collateral effects,
no significant difference was detected between the two Groups. No improvement was
seen in the Female sexual dissatisfaction domain on the GRISS assessment. Conclusion:
A ninety-day treatment using Tribulus terrestris in post-menopausal women with sexual
dysfunction led to improvements in several aspects of sexuality according to scores on the
GRISS questionnaires, applied before and after the treatment. Analysis of post-treatment
responses on the FIEI questionnaire also revealed positive results. These results allow us
to conclude that use of Tribulus terrestris at the doses administered proved effective for
treating sexual disorders in post-menopausal women.
P-51.
The effects of isoflavones derived from Glycine max (L.) Merr. and
conjugated equine estrogen on the vaginal epithelium and endometrium
of postmenopausal women
Sonia Maria Rolim R. Lima, MD, PhD1, Silvia Saito, MD1, Benedito F. Reis, MD1,2,
Sostenes Postigo, MD1, Sheldom R. Botogoski, PhD3, Tsutomu Aoki, PhD1. 1Obstetrics
and Gynaecology, FCMSCSP, São Paulo, Brazil; 2Obstetrics and Gynaecology, UNIVÁS,
Pouso Alegre, Brazil; 3Obstetrics and Gynaecology, UFPR, Curtiba, Brazil
Objective: To compare the effects of isoflavones derived from the extract of Glycine max
(L.) Merr.. and conjugated equine estrogen on the vaginal epithelium and endometrium
of postmenopausal women. Design: Prospective, controlled and not randomized clinical
trial in 90 postmenopausal women, aged from 45 to 68 years old, assessed during three
months and divided into three groups: Group 1 (Isoflavone) n = 30, Group 2 (placebo) n
= 25 and Group 3 (Conjugated Equine Estrogen) n = 20, in which the index of Frost and
the maturation index of vaginal cytology were evaluated, and by transvaginal
ultrasonography the endometrium was evaluated. The results were expressed by the Index
of Meisels and the endometrial thickness measurement in different times (T) 0, 1 and 2.
For statistical analysis, we used the Wilcoxon, Friedman or Kruskal-Wallis test and the
correlations by analyzing the post-hoc Dunn. Results: Group 1: age: 58 years old,
menopausal age: 48 years old, time elapsed since menopause: 9 years. Group 2: age: 57
years old, menopausal age: 48 years old, time elapsed since menopause: 9 years. Group
3: age: 56 years old, menopausal age: 46.5 years old, time elapsed since menopause: 6
years (median values). The start and end values of the index of Meisels in Group 1 were
T0 to T2 3.7: 46.2, Group 2 T0: 0 to T2: 20 and in Group 3 T0: T2 0 to 50 (median values).
The measurements of endometrial thickness at baseline and after 90 days in Group 1 were
T0: 3 and 2 mm, Group 2 T0 to T2 2: 2 mm, and Group 3 T0: T2 3 to 2 mm. Conclusion:
Ninety days treatment with isoflavones derived from Glycine max (L.) Merr. and
conjugated equine estrogens through the vagina of women after menopause demonstrated
that there was an improvement in the symptoms of vaginal atrophy and a significant
increase in the values of cell maturation similar to conjugated equine estrogen. When
comparing Isoflavone and conjugated equine estrogen to placebo, there was a rise in the
Index of Meisels with significant difference. After the treatment, all groups showed no
increase in endometrial thickness, changes in vaginal pH, and serum concentrations of
FSH and estradiol.
P-52.
Assessment of Menopause-Related Symptoms among Perimenopausal
Women with HIV
Sara Looby, PhD, ANP1, Hadine Joffe, MD, MSc2, Alison M. Rope1, Jan L. Shifren, MD,
NCMP3, Steven Grinspoon1. 1Program in Nutritional Metabolism & Neuroendocrine Unit,
Massachusetts General Hospital and Harvard Medical School, Boston, MA; 2Center for
Women’s Mental Health, Massachusetts General Hospital and Harvard Medical School,
Boston, MA; 3Department of Obstetrics and Gynecology, Massachusetts General Hospital
and Harvard Medical School, Boston, MA
Objective: HIV-infected women are living longer and entering the menopausal transition.
Hot flashes, insomnia, anxiety and depressive symptoms are common menopauseassociated symptoms that can affect all women during the perimenopause. Collectively,
these symptoms can be burdensome, interfering with daily function and reducing qualityof-life. However, little is known about the presence and intensity of such symptoms among
the growing number of HIV-infected perimenopausal women. The objective of this study
is to evaluate menopausal symptoms including hot flashes, insomnia, anxiety, and
depression among perimenopausal HIV-infected women compared to perimenopausal
non-infected women carefully matched by age, race, and menstrual patterns. We
hypothesize that perimenopausal HIV-infected women are more likely to experience hot
flashes, insomnia, anxiety, and depression compared to the matched control subjects.
Design: In this cross-sectional evaluation, subjects reported the number of days they
experienced hot flashes in past month and completed the Menopause Rating Scale (MRS;
range 0-44), Hot Flash Related Daily Interference Scale (HFRDIS; range 0-100),
Insomnia Severity Index (ISI; 8-14 sub-threshold insomnia, 15-21 moderate clinical
insomnia), Generalized Anxiety Disorder Assessment (GAD-7; scores 5= mild, 10+=
moderate-to-severe anxiety), and Center for Epidemiologic Studies Depression Scale
(CES-D; >16= significant depressive symptoms). Results: 48 women (26 HIV+, 22 HIV) were studied and were similar in age (47+0.4 vs. 48+0.5), race (65% vs. 55%
non-Caucasian), and menstrual patterns (# of periods in past year: 6+0.5 vs. 6+0.5).
Although the number of days with hot flashes and MRS scores were similar between
groups (HIV+: 18+4.2 vs. Control 12+2.3, P=0.21; MRS: median 14, interquartile range
[IQR] 6.5-22, vs. 9, IQR 5.8-17.3, P=0.27, respectively), perimenopausal HIV-infected
women experienced greater interference of their hot flashes with daily function, compared
to matched controls (HFRDIS: HIV+ 37, IQR 10-61 vs. 9, IQR 0-42.8, P=0.03), and had
more insomnia (ISI: 12, IQR 8-18.3 vs. 9, IQR 2-13.3, P=0.02), anxiety (GAD-7: 7, IQR
4.8-13.3 vs. 4, IQR 2-8, P = 0.03), and showed a trend toward more depressive symptoms
(CES-D: HIV+ 20, IQR 10-25 vs. 11.5, IQR 5-19.5, P=0.08). Conclusion:
Perimenopausal women with HIV experience greater distress related to hot flashes and
have more severe insomnia, anxiety, and depressive symptoms than matched
perimenopausal controls, despite experiencing a similar number of days with hot flashes.
These data suggest that clinicians should assess common menopause-associated
symptoms among perimenopausal HIV+ women because of their deleterious effects on
quality-of-life.
P-53.
Safety, efficacy and use of ultra-low dose 10 mcg vaginal estradiol tablets
JoAnn V. Pinkerton1, Ricardo Maamari, MD, NCMP2, Jeffrey Goldstein2. 1University of
Virginia, Charlottesville, VA; 2Novo Nordisk Inc, Princeton, NJ
Objective: Professional medical societies and regulatory agencies recommend that the
lowest effective dose of estrogen consistent with postmenopausal (PM) treatment goals
and benefits and risks for the individual woman should be the therapeutic goal. Thus,
development of the 10 mcg estradiol (E2) vaginal tablet, which provides the lowest FDA
approved dose to treat atrophic vaginitis, addresses these recommendations. The
objectives were 1) To summarize the efficacy, safety and pharmacokinetic (PK) profile of
the 10 mcg E2 vaginal tablets 2) to understand the utilization and perception of the 10 mcg
E2 vaginal tablets in clinical practice after the discontinuation of the 25 mcg E2 vaginal
tablets. Design: Data from 3 previously published pivotal trials that evaluated the
effectiveness, safety and PKs of the 10 mcg E2 vaginal tablets are presented. Additionally,
new data from a survey of 35 health care providers (HCPs, identified by an independent
market research company as prescribers of the 10 mcg E2 vaginal tablet), conducted
between September 30 and October 15, 2010 are presented. The survey used a hybrid
approach that integrated quantitative components with qualitative interviewing techniques.
The survey assessed 1) type of patients treated with 10 mcg E2 tablets - newly diagnosed,
those switched from 25 mcg E2 tablet or another vaginal estrogen therapy (ET) and 2)
HCPs’ clinical impression of the 10 mcg E2 vaginal tablets. Results: Results of a one-year
efficacy/safety trial (205 subjects randomized to 10 mcg E2 and 104 to placebo) showed
statistically significant improvements in both objective (vaginal maturation, pH, and
vaginal health score at week 2) and subjective parameters (composite score of the most
bothersome symptoms at week 8) of vaginal atrophy in the 10 mcg E2 vaginal tablet
treatment group compared to placebo. The proportions of subjects experiencing adverse
or serious adverse events were comparable across the two treatment groups. To further
evaluate endometrial safety, biopsy data from this trial (n=205) was pooled with biopsy
data from 336 women from an open-label 12-month endometrial safety trial to yield 386
53
Clinical Poster Presentations (continued)
evaluable endometrial biopsies. In this pooled analysis, the observed incidence rate of
hyperplasia/carcinoma was 0.52%. Compared with the reported background incidence
rate of 0 1% in PM women, this indicated that use of 10 mcg E2 vaginal tablets for one
year was not associated with an increased risk of endometrial proliferation. A PK study
in 29 PM women with vaginal atrophy evaluated the systemic absorption of 10 mcg E2
tablets (dosed once daily for 2 weeks, followed by twice weekly for 10 weeks) using the
highly sensitive assay method of gas chromatography mass spectrometry. The mean
plasma E2 concentrations remained within the typically defined postmenopausal range (≤
20 pg/ml) at all timepoints revealing minimal systemic absorption of E2. Shortly after
the availability of the 10 mcg E2 tablets, a research survey with 35 HCPs revealed that
97% of the HCPs accepted the discontinuation of the higher dose 25 mcg E2 tablets. Of
the patients treated with 10 mcg E2 tablets, 39% were newly diagnosed with atrophic
vaginitis, and 42% represented patients switching from 25 mcg to 10 mcg E2 tablets. The
remaining patients (19%) included those switched from other vaginal ET, those that were
hormone-hesitant and had previously refused local ET and those receiving 10 mcg refills.
The reasons stated for treating new patients with 10 mcg E2 tablet included
discontinuation of the 25 mcg E2 tablet, minimal systemic absorption of estrogen,
availability of a new lower dose option and ease of use. An additional reason given for
switching patients from other local estrogen therapies was that the 10 mcg E2 vaginal
tablets were easier for patients to dose correctly. The majority of HCPs expressed positive
perceptions about the 10 mcg E2 tablet and reported good treatment response.
Conclusion: In conclusion, this review reinforces the effectiveness, safety and minimal
systemic absorption of the 10 mcg E2 vaginal tablets in the treatment of symptoms of
vaginal atrophy with an annual estrogen exposure of only 1.14 mg. In addition, results of
the preliminary survey with HCPs indicate a favorable clinical response and acceptance.
P-54.
Lifetime Estradiol Exposure and Risk of Depression during the
Menopausal Transition: The Study of Women’s Health Across the Nation
Wendy Marsh, MD MS1, Joyce Bromberger2, Sybil Crawford, PhD3, John Randolph,
MD4, Hadine Joffe, MD, MSc5, Howard Kravitz, MD6, Claudio N. Soares, MD, PhD,
FRCPC7. 1Department of Psychiatry, University of Massachusetts, Worcester, MA;
2
Epidemiology and Psychiatry, University of Pittsburgh, Pittsburg, PA; 3Preventive and
Behavioral Medicine, University of Massachusetts, Worcester, MA; 4Obstetrics and
Gynecology, University of Michigan, Ann Arbor, MI; 5Psychiatry and Center for Women’s
Mental Health, Massachusetts General Hospital, Boston, MA; 6Psychiatry and Preventive
Medicine, Rush University, Chicago, IL; 7Psychiatry and Behavioral Neurosciences,
McMaster, Hamilton, ON, Canada
Objective: It is unclear why some women are at increased risk of depression while
undergoing the menopausal transition. Endocrinological factors, particularly changes in
estrogen levels, have been hypothesized as contributing to vulnerability to depression
during this reproductive phase. Herein, we examined whether duration of lifetime estrogen
exposure may be associated with perimenopausal depression risk. Design: Data from the
Study of Women’s Health Across the Nation (SWAN) a multi-site longitudinal,
epidemiologic study designed to examine the physical, biological, and psychological
changes of women during their middle and menopausal years was analyzed. In women
who were premenopausal at study entry, premenopausal lifelong estrogen exposure was
estimated as age of first peri- or postmenopausal SWAN visit, minus age of menarche. The
association of duration of estradiol exposure with time to peri- or postmenopausal
depression was estimated using pooled logistic regression (which approximates survival
analysis for interval-censored data) to model time to first annual visit with Center for
Epidemiologic Studies Depression (CES-D) scale score >=16. Results: Of 1727
premenopausal women at entry, 1282 had complete data (N=8495 observations). Average
duration of estradiol exposure was 35.6±3.2 S.D. years. A longer duration of exposure
prior to the menopausal transition was associated with a lower risk of having a CES-D
score >=16 during the transition. In the model adjusted for pre-menopausal depression,
current and ever antidepressant use, site, ethnicity, baseline education, baseline smoking,
baseline age, time in study (to endpoint or censored), the hazard ratio was 0.847 (95% CI
(0.814-0.881), P<0.0001), giving a decrease of 15.3% in the hazard of experiencing
depression for each additional year of premenopausal estradiol exposure. Conclusion: A
longer duration of estradiol exposure prior to the menopausal transition is protective
against experiencing depression during the transition. Estradiol has been shown to
modulate monoaminergic systems involved in mood regulation (serotonin,
norephinephrine); it is unknown how such modulatory effect during premenopausal years
would lead to a protective effect against depression during the menopausal transition.
Additional analyses will further qualify and quantify other variables related to estrogen
exposure, including use of oral contraceptives, pregnancies and lactation.
Acknowledgments: The SWAN has grant support from the National Institutes of Health
(NIH), DHHS, through the National Institute on Aging (NIA), the National Institute of
Nursing Research (NINR) and the NIH Office of Research on Women’s Health (ORWH)
(Grants NR004061; AG012505, AG012535, AG012531, AG012539, AG012546,
AG012553, AG012554, AG012495). The content of this abstract is solely the
responsibility of the authors and does not necessarily represent the official views of the
NIA, NINR, ORWH or the NIH
54
P-55.
Menopausal symptoms by age and therapy type in women with premature
ovarian failure
Kelsey E. Mills, H.BSc, MD1, Maria Velasco2, Wendy L. Wolfman, MD, FRCSC2.
1
Obstetrics and Gynecology, University of Toronto, Toronto, ON, Canada; 2Menopause
Unit, Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada
Objective: Premature ovarian failure (POF) affects 1% of women and causes infertility
and menopausal symptoms. Women may experience long-term health issues including
cardiac disease and low bone mineral density unless they receive estrogen therapy. The
objective of this study was to evaluate womens’ vasomotor, urogenital, and psychological
symptoms using the validated Menopausal Rating Scale (MRS). We also sought to
determine whether any differences existed in symptom severity based on the patient’s
age, as well as the type of estrogen therapy (oral contraceptive pill vs. hormone therapy).
Design: Patients in the POF clinic at Mount Sinai Hospital, Toronto, Canada, were
administered a questionnaire containing demographic and etiologic data as well as the
validated MRS to assess menopausal symptoms. A total score > 9 reflects moderate to
severe symptoms. A small chart review was done to collect additional data. Data was
expressed as mean +/- standard deviation and percentages. Analysis was performed using
OpenEpi (Open Source Epidemiologic Statics for Public Health, 2009). T-tests were used
to analyze continuous data for significance, and Fisher’s Exact Test was used to analyze
categorical data. This study received research ethics approval from Mount Sinai Hospital,
Toronto, Canada. Results: N=44, with 10 people declining to participate. Average age
was 30.9+/- 8.1 years and average age of presentation with POF 26.5+/-9.8 years. Fortyone percent of participants had idiopathic POF. Forty seven percent of respondents used
an oral contraceptive pill (OCP) and 41% of patients used hormone therapy (HT). Ninetytwo percent of women on HT were > than 30 years and 69% of women on OCPs were <30
years. The average MRS total score of all women was 10.4 +/- 6.4. By MRS domain, the
average symptom score for psychological domain was 4.2+/- 2.9, for somatic symptoms
was 3.7 +/-2.8 and for urogenital symptoms was 2.5 +/- 2.8. A comparison by therapy type
(OCP vs. HT) revealed no significant difference between total MRS scores as well as
domain scores. A comparison by age (< vs. > 30yrs) also revealed no significant difference
in total MRS and domain scores. In the analysis of all symptoms evaluated in the MRS,
sexual symptoms and sleep disturbance overall, were the symptoms receiving the highest
scores in our participants. Conclusion: The results show that the overall total MRS score
in our participants was in the moderate range for symptom severity. In comparing the
total MRS and different domain scores by age category as well as by type of estrogen
therapy, we found no statistically significant differences. The symptoms receiving the
highest scores in our patients were sexual and sleep disturbance, which may promote
further assessment and management of these symptoms in women with POF in the future.
P-56.
Assessment of quality of life in a large female Colombian sample using
the Cervantes Scale*
Faustino R Pérez-López1, Alvaro Monterrosa-Castro2, Ivette Romero-Pérez2, Katherin
Portela-Buelvas2, Peter Chedraui3, Ana Maria Fernández-Alonso4. 1Obstetrics and
Gynecology, University of Zaragoza, Zaragoza, Spain; 2Grupo de Investigación de Salud
de la Mujer, Facultad de Medicina. Universidad de Cartagena, Cartagena, Colombia;
3
Instituto de Biomedicina. Facultad de Medicina, Universidad Católica de Santiago de
Guayaquil, Guayaquil, Ecuador; 4Servicio de Obstetricia y Ginecología, Complejo
Hospitalario Torrecárdenas, Almeria, Spain
Objective: To assess quality of life (QoL) with the Cervantes Scale (CS) in a large midaged Colombian female sample. Design: In this cross sectional study, 1,739 healthy
women aged 40-59 were requested to simultaneously fill out the CS and a general survey
containing demographic female and partner data. The CS has four domains: the
menopause and health (15 items), sexuality (4 items), couple relationship (3 items) and
psychic domain (9 items). The CS total score may range from 0 to 155 with higher score
indicating worse QoL. The Kruskall-Wallis test was used for comparisons. Results:
Median CS scores (total and all 4 domains) significantly increased with age, body mass
index (BMI) values and menopausal status (post vs. premenopausal women, p<0.0001).
Alpha Cronbach values were high (internal consistency) for the total CS (0.813) and its
domains: menopause and health (0.813), psychic (0.804), sexuality (0.845), and couple
relationship (0.838). Conclusion: This is the first report of QoL assessment using the CS
in a large mid-aged Latin American (Colombian) female population in which age, BMI
and menopausal status were factors impairing QoL. *This research is a part of the
CAVIMEC (Calidad de Vida en la Menopausia y Etnias Colombianas) Research Program.
P-57.
Ethnical and socio-demographical influences on quality of life in middleaged Colombian women*
Alvaro Monterrosa-Castro1, Angel Paternina-Caicedo1, Liezel Ulloque-Caamaño1, Ana
Maria Fernandez-Alonso2, Peter Chedraui3, Faustino R Pérez-López4. 1Grupo de
Investigación Salud de la Mujer. Facultad de Medicina, Universidad de Cartagena,
Cartagena, Colombia; 2Servicio de Obstetricia y Ginecologia, Complejo Hospitalario
Torrecárdenas, Almeria, Spain; 3Instituto de Biomedicina. Facultad de Medicina,
Universidad Católica Santiago de Guayaquil, Guayaquil, Ecuador; 4Obstetrics and
Gynecology, University of Zaragoza, Zaragoza, Spain
Objective: To evaluate quality of life (QoL) in middle aged Colombian women using the
Cervantes Scale (CS) in order to determine differences according to ethnical and sociodemographical background. Design: A total of 1,739 otherwise healthy women (40 to 59
years) fill out the CS and a general survey containing demographic female/partner data.
Total CS score may range from 0 to 155, higher scores reflecting worse QoL.
Comparisons were performed between mestizo and Afro-descendents (A-d) women using
NAMS11_Regular-LB_Abstracts-2 8/29/11 4:13 PM Page 24
U Mann Whitney or the Kruskall-Wallis test as appropriate. Results: Median scores for
the total CS, and psychical, sexuality and couple relationship domains were significantly
lower in A-d women as compared to mestizo ones (p<0.0001). Health and ageing subdomain scores (included in menopause and health domain) were also significantly lower
in A-d women. Housewives and retired women presented higher total CS scores.
Conclusion: This study found that QoL was related to female ethnical and sociodemographical characteristics. *This research is a part of the CAVIMEC (Calidad de Vida
en la Menopausia y Etnias Colombianas) Research Program.
P-58.
Analysis of the Indication of Treatment of Osteoporosis in Women of a
Primary Care Unit of Spain
Laura Moral1, Rosa Ayuso1, Raimundo Hernando1, Amanda Lopez2. 1Primay Care
Medicine, OSAKIDETZA, Vitoria, Spain; 2Research Unit, OSAKIDETZA, Vitoria, Spain
Objective: Assess whether the indication of osteoporosis drug therapy is suited to the
NAMS recommendations in 2010 included in our clinical practice guideline. Design:
Sectional study conducted in an urban health center (CS Olaguibel, Vitoria, Spain) The
participants were all postmenopausal women who have been treated with
bisphosphonates, raloxifene, strontium ranelate or teritapamida between May 18, 2009
and May 18, 2010 In order to determine the appropriateness of the treatment, we set
parameters such as hip fracture or vertebral, densitometric values, risk factors and FRAX.
Given the heterogeneity of the origin of the limitation in our field, it seemed interesting
to sort by specialty, to determine if significant differences between them regarding the
appropriateness of prescribing. Results: Of the 1021 patients included, the average age
was 71.5±11 years. 25 were excluded from analysis by cessation of therapy during the
study period. In the final sample (996 patients) the most prescribed drugs were risedronate
(33%) and alendronate (26.7%). Among the gynecologists the most prescribed drugs were
ibandronate (22.6%), alendronate + Vitamin D (20.4%) and raloxifene (18.3%)while in
primary care were alendronate (38.7%) and risedronate (33.5 %), raloxifene was
prescribed only in 1,9%. An analysis of the prescription by densitometry, 59.1% (n = 55)
of patients were successfully treated by gynecologists versus 40.2% (n = 188) primary and
40.7% (n = 135) of specialist (p = 0.002). About the proper prescription including FRAX
and previous fractures, 66.7% (n = 60) of patients cared in gynecology were correctly
treated compared to 62.9% (n = 288) primary and 69% (n = 227) without detecting
significant differences. Conclusion: Despite the current ease of access by the doctor for
diagnostic tests, one third of women are treated inadequately. No significant differences
were found regarding the origin of the prescription, however, the pharmacological pattern
is variable. Primary Care is to be the best suited to the treatment recommendations of the
guidelines, prescribing bisphosphonates as first choice. On the contrary, there is a
preference of gynecologists and ibandronate as the drug of first use and no evidence of
their effectiveness in reducing the risk of hip fracture, with a high percentage of
prescription of raloxifene (indicating an alternative to bisphosphonates in our country)
Assess treatment adherence barriers and promote adherence; provide clear information
about fracture risk and treatment purpose.
P-59.
A Prospective Study of DT56a (Femarelle®) for the Treatment of
Postmenopausal Vaginal Atrophy
Margaret Nachtigall1, Frederick Naftolin, MD PhD1, Richard Nachtigall1, Israel Yoles,
MD2, Lila E. Nachtigall, MD, NCMP1. 1Ob/Gyn, NYU Medical School, New York, NY;
2
Se-cure pharmaceuticals, Dalton, Israel
Objective: Symptomatic vaginal atrophy affects one out of three menopausal women.
Hormone therapy, both systemic and local, is effective and indicated for the relief of this
problem but may not be acceptable to all patients. DT56a (Femarelle®), a selective
estrogen receptor modulator derived from botanical source, was found to be effective at
decreasing menopausal hot flushes and increasing bone mass. We performed a pilot study
testing the use of DT56a for vaginal atrophy. Design: 12 post-menopausal women with
vaginal atrophy (<5% superficial cells on cervical cytology) with at least one moderateto-severe symptom, were recruited for an IRB-approved 12-week open-label pilot study.
DT56a (322mg) was given by mouth 2X/day for 12 weeks. At each visit (0&q4 weeks)
subjects had a vaginal atrophy assessment (speculum exam, vaginal pH) and completed
questionnaires on atrophy symptoms and quality of life (Utian QoL scale).At weeks 0
and 12, a pap smear with maturation index and vaginal cultures were performed. Results:
The main bothersome symptoms were: Dyspareunia- 5 Patients,Vaginal soreness- 3
Patients,Vaginal dryness- 2 Patients,Vaginal irritation-1 Patient and Bleeding with coitus1 Patient. All patients reported significant improvement in their most bothersome
symptom. All women had a significant reduction in vaginal pH. The average pH went
from baseline 7.7±2.2 to 4.9±1.4 on week 12,p<0.0001. The maturation index also
improved as shown in the figure below: Parabasal cells that were 100% at entry were 43%
following 12 weeks of treatment, Intermediate cells were changed from 0 to 47% and
Superficial cells that were 0 at entry, were 10% following 12 weeks of treatment with
DT56a (all statistically significant, p<0.001). A significant improvement was found in
UQoL index from mean pre-treatment of 75.4±22.7 points to mean post-treatment of
88.9±26.8, p<0.001.In the sexual domains of the UQoL there was a significant
improvement from 6.5±2 points (mean pre-treatment) to 10.6± 3.2 (mean post-treatment),
p<0.001. Conclusion: In this open-label prospective study DT56a was effective against
symptomatic vulvo-vaginal atrophy in both subjective and objective measures. The
changes in symptoms and pH were prompt and paralleled symptomatic relief. DT56a
furnished a significant improvement in UQoL. As the placebo effect on the maturation
index and vaginal pH is negligible, this 12 patient study provides an indicative
measurement of the positive effect of DT56a for the treatment of vulvo-vaginal atrophy
and a large double blind placebo controlled trial is planned.
Comparison of correct treatment between gynecology and primary care
Gynecology prescribe better but the difference is statistically significant
Drugs prescribed by primary care and gynecology
P-60.
Estimation of cardiovascular risk in postmenopausal women
The prescription pattern differs by specialty. Primary care is who best suited to
the recommendations of the guidelines.
Eliana A. Nahas, MD, Aline M. Andrade, Jorge Nahas-Neto, Mayra C. Jorge, Claudio L.
Orsatti, Ana Paula Tardivo. Gynecology and Obstetrics, Botucatu Medical School-Sao
Paulo State University, Botucatu, Brazil
Objective: to compare estimation of cardiovascular risk using the Framinghan risk score
(FRS) and the presence of the metabolic syndrome (MetS) in postmenopausal women in
primary cardiovascular disease (CVD) prevention. Design: In this cross-sectional study,
a total of 497 Brazilian postmenopausal women, with age ≥ 45 years and amenorrhea >12
months were included. Those had been diagnosed with or were being treated for heart
disease, cerebrovascular disease, chronic kidney disease, or diabetes were excluded. The
percentage risk of coronary heart disease (CHD) was calculated using the FRS that
includes age, total cholesterol, HDL-cholesterol, systolic blood pressure, and ciga¬rette
smoking. A risk greater than 20% is considered high; a risk of 10% to 20% is intermediate;
and a risk of less than 10% is low. According to the US National Cholesterol Education
Program Adult Treatment Panel III guidelines, MetS was diagnosed in subjects with three
or more of the following: waist circumference (WC) >88 cm, blood pressure ≥130/85
mmHg, triglycerides ≥150 mg/dl, HDL-cholesterol <50 mg/dl and glucose >100mg/dl.
Data on antecedents, anthropometric indicators, and values of C-reactive protein (CRP)
were collected. For statistical analysis were used: Chi-square test or Fisher’s exact test,
and logistic regression method (odds ratio-OR). Results: The mean age of the patients
55
Clinical Poster Presentations (continued)
included was 55.3 ± 7.0 years, time since menopause of 7.2 ± 5.9 years, and BMI values
of 28.2 ± 5.3 kg/m2. According to FRS, among 497 women, mean absolute risk for
developing coronary events in 10 years of 3.0%, of which 72.4% (360/497) of women
were classified as low risk, 16.5% (82/497) of intermediate risk and 11.1% (55/497)
presenting a high risk for CHD. The MetS was identified in 40% (199/497) of the women.
Among the patients at risk for CHD by FRS 46.2% had MetS while 84.9% of women
without MetS were classified as low risk (p<0.001). The risk for CHD increased
significantly with age at menopause (OR 1.10; CI 95% 1.04-1.17), time since menopause
(OR 1.13; CI 95% 1.08-1.18), elevated triglycerides (OR 1.03; CI 95% 1.0-1.10), and
presence of MetS (OR 1.72; CI 95% 1.48-1.84). The BMI, WC, exercise, use of hormone
therapy and elevated CRP did not influence the risk. Conclusion: Using only the FRS in
estimation of cardiovascular risk, a substantial number of postmenopausal women
showing evidence of the MetS were not identified, even though women with the MetS are
at higher risk of CVD. *Financial support by FAPESP with scientific initiation
scholarship; process number 2009/15659-2.
P-61.
Are Case Reports of Black Cohosh Hepatotoxicity Conclusive? No
Evidence by Metaanalysis of Randomized Controlled Clinical Trials
Belal Naser1, Susana Garcia DeArriba1, Klaus-Ulrich Nolte1, Jörg Schnitker2, Mary Jane
Minkin3, Rüdiger Osmers4. 1Pharmacovigilance, Schaper & Brümmer GmbH & Co. KG,
Salzgitter, Germany; 2Institute for Applied Statistics, IAS Dr. Schnitker, Bielefeld,
Germany; 3Obstetrics and Gynecology, Yale University School of Medicine, New Haven,
CT; 4Obstetrics and Gynecology, Hildesheim General Hospital, Hildesheim, Germany
Objective: Black cohosh (BC; Actaea racemosa), is a popular and safe treatment option
in the management of menopausal complaints. Despite of the long-term experience with
BC-based preparations, a number of case reports among its users with suspected
hepatotoxicity have been put into the center of attention in recent years. This, however,
is in clear contrast to results from randomised clinical trials (RCTs), where no signs of
liver toxicity risk have been observed until now. Design: To study this discrepancy, a
metaanalysis of RCTs on the efficacy and safety of black cohosh was conducted regarding
liver function tests. In a second step, the data was analysed in light of evaluations of case
reports and events from the spontaneous reporting. Results: A total of forty studies were
identified in the scope of the metaanalysis. Seven studies on breast cancer survivors were
excluded. From the remaining 33 studies on relatively healthy peri- and post-menopausal
patients, 17 RCTs (n= 2486 patients) were considered for further evaluations, and 5 RCTs
(test population = 517 and reference population = 503) could finally be included in the
metaanalyses. No significant effect of the tested isopropanolic BC containing preparations
on liver functions could be demonstrated. Whereas our findings are in agreement with
other results of numerous RCTs with treatment durations of 3-12 months and doses of 40128 mg BC/d, there is a clear contrast to the quantity of case reports published in the
literature and/or spontaneously received by manufacturers and medicinal agencies.
Depending on the causality assignation scales, however, assessments of these reports were
extremely variable. Initial causality assessments have primarily been based on an ad hoc
evaluation. However, thorough analysis based on quantitative and liver specific methods
disclosed many confounding variables, which can explain the inconsistencies between
findings from the spontaneous reporting and clinical studies. Adulteration, unclear
declaration of BC products, low quality of clinical data, undisclosed co-medication, comorbidity, lack of temporal association, and other fea-tures are some of the confounding
variables. Conclusion: In contrast to case reports, our metaanalysis did not detect any
adverse effect of the isopropanolic BC-extract on liver functions. In addition, there is a
growing body of recent re-evaluations using structured causality scales, which confirm the
findings of RCTs regarding the lack of BC-hepatotoxicity.
P-62.
Self-Reported Vasomotor Symptoms and Dietary Isoflavones: Results
from the LeAVES Study
Katherine M. Newton, PhD1, Johanna Lampe, PhD2, Susan D. Reed, MD, MPH3,2, Congh
Qu, PhD3, Sharon Fuller1, Gabrielle Gundersen, MS1. 1Group Health Research Institute,
Seattle, WA; 2Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle,
WA; 3Obstetrics and Gynecology, Univeristy of Washginton, Seattle, WA
Objective: Questions remain about the impact of soy isoflavones on vasomotor
symptoms. Many of the studies to date have evaluated the effects of isoflavone dietary
supplements. We sought to describe self-reported hot flashes, night sweats, and bother
by dietary (non-supplement) isoflavone consumption among women who were in the
menopause transition or postmenopausal. Design: We conducted a population-based
postal survey of women aged 45-58 at Group Health Cooperative in Washington State;
9,273 of 18,500 women responded (50% response rate). The questionnaire included
information on reproductive stage, frequency and bother of hot flashes and night sweats,
demographic characteristics, and soy food intake (validated Lampe Soyfood
Questionnaire). At total of 5,635 were eligible for these analyses after excluding women
who were premenopausal, who were using contraceptive or non-contraceptive hormones,
who were missing data on hot flashes or night sweats, or who did not complete the
Soyfood Questionnaire. Mean daily isoflavone intake (genistein plus daidzein) was
categorized as none (n=1821), low (<=4.3mg/day, n=1928), or high (>4.3mg/day,
n=1886). Values were set, by design, to divide women into tertiles of isoflavone
consumption. Analyses used descriptive statistics and generalized linear models
controlling for age and race/ethnicity. Results: Despite some statistically significant
differences, there were no clinically meaningful differences between women with no, low,
or high isoflavone intake (respectively) in any study measures of vasomotor symptoms,
including : hot flashes ever (82%, 83%, 81%); hot flashes in the last two weeks (54%,
56%, 57%); mean number of hot flashes per day (4.14± 5.72, 3.95± 6.12, 4.23± 6.04); >
56
8 days with hot flashes in the last two weeks (43%, 39%, 42%); bothered by hot flashes
moderately/a lot vs. little/not at all (58%, 56%, 57%); night sweats ever (72%, 75%, 72%);
night sweats in the last two weeks (35%, 30%, 34%); mean night sweats per night (2.18±
2.17, 1.96± 1.64, 2.08± 4.12); > 8 days with night sweats in the last two weeks (35%, 30%,
34%); or bothered by night sweats moderately/a lot vs. little/not at all (62%, 64%, 62%).
Conclusion: We found little evidence of variation in vasomotor symptoms by total soy
isoflavone consumption in a large, population-based study. Further analyses will focus on
isoflavone type (genistein, daidzein) and, in a subset of women, whether these associations
are influences by equol producer status.
P-63.
Self-Reported Vasomotor Symptoms and Pain by Detailed Race/Ethnicity:
Results from the LeAVES Study
Katherine M. Newton, PhD1, Johanna Lampe, PhD2, Susan D. Reed, MD, MPH3,2, Congh
Qu, PhD2, Sharon Fuller1, Gabrielle Gundersen, MS1. 1Group Health Research Institute,
Seattle, WA; 2Public Health Sciences, Fred Hutchenson Cancer Research Center, Seattle,
WA; 3Obstetrics and Gynecology, University of Washington, Seattle, WA
Objective: Differences in menopause symptoms by race/ethnicity have been reported in
the literature, but broad categories often used, particularly for “Asian/Pacific Islanders”.
It has been reported that Japanese women may be more likely to experience aches and
pains than vasomotor symptoms during the menopause. The purpose of this study was to
describe self-reported hot flashes, night sweats, bother from hot flashes and night sweats,
and joint pain, by more detailed categories of race/ethnicity. Design: We conducted a
population-based postal survey of women aged 45-58 at Group Health Cooperative in
Washington State; 9,273/18,500 responded (50% response rate). The questionnaire
included information on reproductive stage, frequency and bother of hot flashes and night
sweats, whether women were bothered by headaches or body aches and pains,
demographic characteristics, and a detailed questionnaire on race/ethnicity. A total of
5,645 women were eligible for this analysis after excluding women who were
premenopausal, using contraceptive or non-contraceptive hormones, or were missing data
on hot flashes, night sweats, or race/ethnicity. Analyses were controlled for age and
hysterectomy. Analyses used descriptive statistics and logistic regression models
controlling for age and hysterectomy. (*P<0.05; †P<0.01; ‡ P<0.001) Results: The
number of participants by race was: non-Hispanic white (n=4,422); Hispanic white
(n=139); Hispanic non-white (n=64); African-American (n=230); American Indian
(n=92); Asian Indian (29); Chinese (n=161); Filipino (n=126); Japanese (n=127);
Vietnamese (n=46); other Asian (n=81); Native Hawaiian (n=15); other Pacific Islander
(n=20); and other (n=93). After controlling for age and hysterectomy, as compared with
non-Hispanic white women (84%), Chinese (64%‡), Filipino (74%†), Japanese (63%‡),
Vietnamese (54%‡) and other Asian (68%‡) women were significantly less likely to report
ever having had hot flashes. As compared with non-Hispanic white women (58%),
Hispanic non-white (47%†), Chinese (37%‡), Filipino (40%‡), Japanese (45%‡),
Vietnamese (29%‡), other Asian (63%‡) and native Hawaiian (67%†) women were
significantly less likely to report every having had night sweats. As compared with nonHispanic white women (58%), African American women reported significantly more
bother from hot flashes (69%†), while Chinese (37%†) and Filipino (40%†) women
reported significantly less bother from hot flashes. As compared with non-Hispanic white
women (65%), Hispanic non-white (38%†), Asian Indian (41%†), Chinese (44%†),
Filipino (40%‡) and Japanese (40%†) women reported significantly less bother from night
sweats. As compared with non-Hispanic white women (61%), African-American (70%*)
and women categorized as “other” (75%†) were significantly more likely to report being
bothered by joint pain, while Chinese (52%*), Japanese (51%*), and other Asian (49%*)
women were significantly less likely to report being bothered by joint pain. Conclusion:
In this population-based study of women residing in the Pacific Northwest, we found
significant variation in the reporting of vasomotor symptoms, degree of bother related to
these symptoms, and complaints of bother related to joint pain among women of differing
race/ethnicities. While our study confirms that reporting of vasomotor symptoms is higher
among African American women, and lower among Asian women, than among white
women, we found that, contrary to other reports, Japanese women were less likely to
report being bothered by aches and pains than were white women.
P-64.
An Evaluation of the Effect of Desvenlafaxine 100 mg on the
Pharmacokinetics of Tamoxifen in Postmenopausal Women
Alice I. Nichols, PhD1, Shannon Lubaczewski, PharmD, MS1, Yali Liang, MS1, Kyle
Matschke, MAS1, Gabriel Braley2, Tanya Ramey, MD, PhD2. 1Pfizer Inc, Collegeville,
PA; 2Pfizer Inc, Groton/New London, CT
Objective: Because the efficacy of the selective estrogen receptor modulator tamoxifen
is partially dependent on cytochrome P450 2D6 (CYP2D6) mediated metabolism to form
2 primary active metabolites (ie, 4-hydroxy-tamoxifen and endoxifen), there is a concern
about the potential risks associated with coadministering any potent CYP2D6 inhibitor
with tamoxifen. A body of data is developing that suggests tamoxifen patients receiving
concomitant treatment with a CYP2D6 inhibitor, such as the antidepressant paroxetine,
have poorer treatment outcomes compared with those with normal levels of CYP2D6
activity. Design: This open-label study was designed to determine the effect of
coadministering desvenlafaxine on tamoxifen pharmacokinetics. The study enrolled
healthy, postmenopausal women and had a 2-period inpatient (period 1: 3 days; 2 nights;
period 2: 9 days; 8 nights) and outpatient (period 1: 11 visits; period 2: 21 visits) design.
On study day 1 of period 1, subjects were administered tamoxifen 40 mg followed by 23
days of blood sampling for pharmacokinetic analyses. During period 2, subjects were
administered desvenlafaxine 100 mg alone for 7 days to reach steady state, then a single
dose of tamoxifen 40 mg was coadministered followed by 23 days of blood sampling.
The primary outcomes were the pharmacokinetics of tamoxifen and endoxifen (ie, AUC
over infinite time (AUCinf), AUC to the last measurable concentration [AUClast], and
peak plasma concentration [Cmax]). Secondary outcomes included the pharmacokinetics
of 4 hydroxy-tamoxifen and N desmethyl-tamoxifen, concentrations of tamoxifen and its
metabolites (4 hydroxy-tamoxifen, N desmethyl-tamoxifen and endoxifen). Safety and
tolerability of desvenlafaxine and tamoxifen were also assessed. Comparisons between
monotherapy and combination therapy were made using the ratio of adjusted mean
differences and corresponding 90% confidence intervals (CIs). The test for interaction
was considered negative if the 90% CIs for the ratios of (Test [desvenlafaxine +
tamoxifen]/Reference [tamoxifen]) were within 80% to 125%. Results: Coadministration
of tamoxifen with steady state desvenlafaxine did not alter tamoxifen AUCinf, AUClast
and Cmax, as reflected by the ratio of adjusted geometric means (90% CI) of
approximately 100.7% (96.7%, 104.9%), 103.5% (100.2%, 106.9%), and 99.4% (94.0%,
105.2%). The AUCinf, AUClast, and Cmax for 4-hydroxy-tamoxifen were not altered as
reflected by the ratio of adjusted geometric means of 105.6% (99.7%, 111.8%), 109.3%
(103.5 %, 115.5%), and 108.5% (103.5%, 113.7%). Because concentrations of endoxifen
and N-desmethyl-tamoxifen were detected immediately prior to the second dose of
tamoxifen, the pharmacokinetic parameters for these 2 analytes were adjusted for
carryover. In addition, only AUClast and not AUCinf could be accurately calculated for
these 2 metabolites. Coadministration of desvenlafaxine and tamoxifen did not alter Ndesmethyl-tamoxifen AUClast and Cmax, as reflected by the ratio of adjusted geometric
means of 104.2% (100.9%, 107.6%) and 112.1% (107.4%, 116.9%). Endoxifen AUClast
and Cmax decreased by approximately 11.8% and 8.0%, as reflected by the ratio of
adjusted geometric means of 88.2% (82.6%, 94.2%) and 92.0% (84.7%, 100.0%).
However, this change was not significant as the 90% CI for the ratio of adjusted means
fell wholly within the prespecified acceptance range (80%, 125%). There were no new,
unexpected safety concerns observed in this study. The most common adverse events were
constipation, nausea, and insomnia. Conclusion: There was no interactive effect on
tamoxifen pharmacokinetics with steady state of desvenlafaxine 100 mg compared with
tamoxifen alone. For tamoxifen, 4-hydroxy-tamoxifen, N-desmethyl-tamoxifen and
endoxifen, the 90% CIs for the ratios of adjusted mean for AUCs and Cmax lie within the
prespecified acceptance range of 80% to 125%. Due to the lack of effect of desvenlafaxine
on tamoxifen pharmacokinetics, usage of desvenlafaxine in women being treated with
tamoxifen may offer a treatment option that will unlikely alter the efficacy of tamoxifen.
P-65.
Mamimal Oxygen Uptake and Body Composition in Non-Obese and
Obese Postmenopausal Women
Betania Ogando1,2, Josiane Rocha1,2, Ronaldo Gabriel2, Helena Moreira2. 1Unimontes,
Montes Claros, Brazil; 2University of Trás-os-Montes and Alto Douro, Vila Real, Portugal
Objective: The purpose of this study was to compare maximal oxygen uptake (VO2max)
and variables of body composition in non-obese and obese postmenopausal women, as
well as to verify the effect of these variables on cardiorespiratory fitness in the two
examined groups. Design: The sample was composed of 208 postmenopausal women
(55.57±6.62 years), 56% (75.5%) with a menopause period inferior to 10 years, 55% were
non-users of hormone therapy and 74% were obese. Weight (W), fat mass (FM), visceral
fat area (VFA), skeletal muscle mass (SM) and regional soft lean mass (arms, trunk and
legs) were evaluated by octopolar bioimpedance InBody 720 (Biospace) and the basal
metabolic rate (BMR) was measured resorting to the use of the Cunningham equation
(1991). Skeletal muscle mass index (SMI) was calculated with the formula SMI= (SM/W)
x 100 and VO2max was assessed with the Modified Bruce protocol. The cutpoints for
obesity and high visceral adiposity were, respectively, FM≥35% and VFA ≥100 cm2. The
degree of association between variables was calculated with the Pearson’s correlation
coefficient and a multiple linear regression analysis was performed. Student’s t test was
used to compare the means and the level of significance was set at 5%. Results: Obese
women presented higher values (p≤0.01) of age (2.25 years), FM (12.20%) and VFA
(39.37 cm2) and lower values of SMI (-6.42%), VO2max (-4.77 ml/kg/min), compared
to nonobese women, not being differences identified on BMR. Regardless of age,
characteristics of menopause and other variables of body composition, VFA explains 13%
(β=-0-356, p=0.01) and 19% (β= -0.434, p<0.01) of VO2max in non obese and obese
women, respectively. The former presented a worsening in the levels of VO2max and
approximately 3.30 ml/kg/min in the presence of an increased level of central adiposity.
In what regards obese women, the average difference of VO2max among women with a
high VFA (between 100 and 150 cm2) and very high VFA (superior to 150 cm2) was 3.72
ml/kg/min (p< 0.01). Conclusion: The study suggests that visceral fat area is a significant
independent predictor of cardiorespiratory fitness in non-obese and obese postmenopausal
women. Obesity tends to be related to a high VFA and a low SMI.
P-66.
Evaluation of the deficiency of Vitamin D in a population of climacteric
women in Brazil – Pilot Study
Marcia A. Padua, Ji H. Yang, Roberta Vasconcelos, MD, Carolina Martins, MD, Clarissa
Fujiwara, MD, Maria Cristina Stefano. Multidisciplinary Study Group in Quality of Life,
Clinica Synesis, São Paulo, Brazil
Objective: Vitamin D serum dosage evaluation in 70 climacteric women submitted to
the World Health Organization Healthy Life Quality – SHORT FORM 36 (SF-36).
Design: Cross-sectional, random study of 70 climacteric patients in a private practice,
submitted to the SF-36 questionnaire and to a Vitamin D serum dosage. Results: Average
age is 51,15 years (± 7,31); 94 % of participants have a college degree. The great majority
displays skin pigmentation between levels II (40 %) and II/III (55 %), according to the
Fitzgerald Skin Types, and 75,7 % of them relate scarce sun exposure. The average dosage
of Vitamin D is 21,10 ng/mL (± 7,11); insufficient levels of Vitamin D was detected in 86
% of the patients. However, the analysis of the SF-36 revealed positive perception of both
physical and mental health, with more than 70% of favorable answers to the items
analysed, including degree of pain, vitality, physical aspects, functional capacity, social
and emotional aspects, and mental health. In spite of that, 92.5 % declare little leisure
time. Conclusion: The reduction of Vitamin D was positively related with low sun
exposure, not associated with skin color or quality of life. Based on these results, the high
incidence of hypovitaminosis D in women from a tropical country leads us to suggest the
importance of a routine dosage of Vitamin D.
P-67.
One-year Maintenance of Efficacy and Safety of Desvenlafaxine in
Women With Vasomotor Symptoms Associated With Menopause
Joann V. Pinkerton1, David F. Archer2, Christine J. Guico-Pabia, MD, MBA, MPH3,
Eunhee Hwang3, Ru-fong J. Cheng3. 1University of Virginia Health System,
Charlottesville, VA; 2Eastern Virginia Medical School, Norfolk, VA; 3Pfizer Inc,
Collegeville, PA
Objective: Desvenlafaxine (administered as desvenlafaxine succinate) is a nonhormonal
serotonin-norepinephrine reuptake inhibitor under development for treatment of moderate
to severe vasomotor symptoms (VMS) associated with menopause. The 12-month efficacy
and safety of desvenlafaxine 100 mg/d were assessed in a multicenter, double-blind,
randomized, placebo-controlled trial in postmenopausal women seeking treatment for
bothersome VMS. Design: The reduction in average daily frequency and severity of hot
flushes (HF) at week 12 and maintenance of effect at months 6 and 12 were evaluated in
a subset of women experiencing ≥7 moderate to severe HF a day or ≥50/wk for ≥2 weeks
(modified intent to treat [MITT] efficacy substudy population) and analyzed using analysis
of covariance with treatment as a factor and baseline value as a covariate. Greene
Climacteric Scale (GCS), Patient Global Impression Symptom Rating (PGI-R), and
Patient Global Impression of Change (PGI-C) scores, and safety data were also evaluated
in the entire population. Results: A total of 2186 patients were randomly assigned to
treatment. Primary short-term (week 12) outcomes for the subset of 365 women in the
MITT efficacy substudy population have been presented earlier. Mean frequency of
moderate and severe HF at baseline was 12/d, and mean HF severity score was 2.4. At
months 6 and 12, the frequency and severity of HF were significantly reduced for
desvenlafaxine vs placebo (P≤0.003). At 1 year, desvenlafaxine reduced HF frequency
by 7.7 moderate and severe HF/d and severity score by 0.75 (placebo, −4.8/d and −0.44).
For the entire population (main study efficacy population: n=964 desvenlafaxine, n=986
placebo), reductions in GCS total score and 4 of 6 subscales (anxiety, depression,
psychological symptoms, and VMS) were significantly greater with desvenlafaxine
compared with placebo at 6 and 12 months (P<0.001). Women taking desvenlafaxine
reported greater improvement vs placebo at 6 and 12 months based on PGI-C scores and
change in PGI-R scores (all P<0.001). Treatment-emergent adverse events were reported
by 84% of women taking desvenlafaxine and 79% taking placebo. Serious adverse events
occurred in 4.0% of women in the desvenlafaxine group and 3.4% in the placebo group.
Laboratory test values, vital sign measurements, and ECG results did not suggest any
adverse safety signal during the 12 months of the study. Full safety results are reported
separately. Conclusion: Treatment efficacy achieved at week 12 with desvenlafaxine 100
mg/d in postmenopausal women with VMS was maintained for one year.
P-68.
Positive Effect of Gabapentin Extended-Release (G-Er) on Sleep in PostMenopausal Women with Vasomotor Symptoms in Breeze 1 Study
Risa Kagan, MD1, Verne E. Cowles, PhD2, David Portman, MD3, Rekha M.
Sathyanarayana, MS2, Michael Sweeney, MD2. 1Alta Bates Summit Medical Center,
Berkeley, CA; 2Product Development, Depomed, Inc, Menlo Park, CA; 3Columbus Center
for Women’s Health Research, Columbus, OH
Objective: To evaluate the effects of G-ER 1200mg (single evening dose) & 1800mg
daily (dosed asymmetrically) on sleep using the Pittsburgh Sleep Quality Index (PSQI)
in post-menopausal women with vasomotor symptoms. Design: This was a Phase 3,
double-blind, placebo-controlled study conducted at 48 sites in the US. Post-menopausal
women with ≥ 7 moderate to severe hot flashes per day during a 7 day baseline period
were randomized in a 1:1:1 ratio to either 1200 mg QD or 1800mg (600mg AM/1200 mg
PM) of G-ER or placebo. Additional inculsion criteria were no history of malignancy
within 2 yrs, and amenorrhea for at least 1 yr or amenorrhea for 6-12 mos with FSH > 40
mIU or ≥ 6 mos post bilateral oophorectomy with or without hysterectomy Patients were
titrated to their randomized dose over 1 wk. The study medication was taken with a meal.
The PSQI consists of 7 components and a derived Global score. PSQI was administered
during clinical visits at randomization and wk 4, 12 & 24 of the stable dosing period. An
ANCOVA model which included treatment and center factors, and the corresponding
baseline value as the covariate was used to determine the pairwise difference between G
ER treatment and placebo treatment. Results: Out of 541 patients randomized 531 were
included in the ITT population for evaluation of PSQI. For both the 1200 mg and the
1800 mg doses the Global Score was improved throughout the study. For the 1800 mg
dose the components of sleep disturbance, quality, latency, duration, and efficiency were
significantly improved compared to placebo at wk 4. At wk 12 sleep disturbance, and
quality were significantly different from placebo, while at wk 24 sleep duration, quality
and efficiency were significantly different from placebo. For the 1200 mg dose sleep
disturbance, quality, duration, efficiency and medication were significantly different from
placebo at wk 4, while at wk 12 quality, duration, and efficiency were significantly
different from placebo and at wk 24 sleep quality and efficiency were significantly
different from placebo. Conclusion: The results from this study suggest that G-ER may
have a beneficial effect on sleep as measured by the PSQI in post-menopausal women
with vasomotor symptoms.
See table on next page.
57
NAMS11_Regular-LB_Abstracts-2 8/29/11 4:13 PM Page 27
Clinical Poster Presentations (continued)
Summary of PSQI Components. Mean Difference from Placebo for Gabapentin ER
P-69.
Symptoms of depressed mood, disturbed sleep and sexual problems in
midlife women: cross- sectional data from the Study of Women’s Health
Across the Nation (SWAN)
Beth Prairie, MD, MPH1, Stephen R. Wisniewski, PhD2, James Luther, MA3, Rachel
Hess4, Rebecca C. Thurston, PhD7,5, Robin Green6, Katherine Wisner7,1, Joyce
Bromberger7,2. 1Ob/Gyn, University of Pittsburgh, Pittsburgh, PA; 2Epidemiology,
University of Pittsburgh, Pittsburgh, PA; 3Epidemiology Data Center, University of
Pittsburgh, Pittsburgh, PA; 4Medicine and Center for Research on Health Care, University
of Pittsburgh, Pittsburgh, PA; 5Psychology, University of Pittsburgh, Pittsburgh, PA;
6
Obstetrics and Gynecology, Albert Einstein College of Medicine, Bronx, NY; 7Psychiatry,
University of Pittsburgh, Pittsburgh, PA
Objective: Depression is known to be associated with both sleep disturbance and sexual
problems in midlife women. These three symptoms may co-occur and represent a
particular symptom complex during midlife. These symptoms are commonly reported but
there are minimal data to examine whether they co-vary in individual women. We sought
to evaluate the interrelatedness of symptoms of depressed mood, disturbed sleep and
sexual problems in the SWAN cohort at single study visit and to characterize women
exhibiting this symptom complex with respect to demographic, psychosocial and clinical
characteristics. We hypothesized that women with this complex of symptoms would have
more stressful life events, lower social support, and be in the late peri-menopausal stage.
Design: SWAN is a multi-ethnic observational cohort study of the menopausal transition
in women across the United States. Demographic information was acquired at baseline,
and menopausal status was assessed at the time of the study visit. Depression was assed
using the Center for Epidemiological Studies Depression Scale (CES-D) with a total score
>= 16 indicating high levels of depressive symptoms. Sleep disturbance was defined as
reporting waking at night, waking early, or difficulty falling asleep at least 3 times in each
of the past 2 weeks. Sexual function was assessed by self-report on a 20-item
questionnaire derived from several sources and addressing multiple domains of sexual
function, including desire, arousal, satisfaction, orgasm and vaginal dryness. Women were
identified as having a sexual problem if they had a problem in any of these five domains.
Women who reported all 3 symptoms were compared to those who did not. Logistic
regression models were used to estimate the association of the demographic, psychosocial
and clinical characteristics with the symptom complex. P values <=0.05 were considered
statistically significant. Results: Study subjects (N=1716) were 49.8 years old on average,
49.7% Caucasian, 24.2% African-American, 10.1% Japanese, 9.3% Chinese and 6.7%
Hispanic. The majority were either early or late peri-menopausal, married, not using
hormone therapy, and rated their overall health as excellent or very good. 16.5% had CESD scores >=16, 36.6% had a sleep problem, and 42.2% had any sexual problem. Five
percent of the women (N=90) experienced all 3 symptoms. In multivariable models,
women with the symptom complex were more likely to have lower household incomes,
less education, be surgically postmenopausal (OR 3.37 (95% CI: 1.56, 7.26))or late perimenopausal (OR 1.99 (95% CI: 1.06, 3.75), rate their general health as fair or poor, have
a higher number of stressful life events and lower social support. No effect was noted for
race/ethnicity or for hormone therapy, although few women (19.8%) were using
hormones. Conclusion: In this cross-sectional analysis of the SWAN cohort, 5% of
women were affected by the complex of symptoms of depressed mood, disturbed sleep
and sexual problems. The predicted prevalence of this symptom complex in this sample
if each of these symptoms were completely independent would be 2.6%. The higher
prevalence found in this analysis suggests that these symptoms do co-vary within
individual women and are interrelated. The association with menopausal stage supports
the hypothesis that this complex is related to the menopausal transition, with surgically
post-menopausal at particularly high risk for having this complex. Psychosocial factors
which are known risk factors for depression, including poor social support and more
stressful life events, were also risks for having the symptom complex. Thus, during
midlife, these symptoms may be more likely to cluster in peri-menopausal women with
these risk factors.
58
P-70.
Sexual function and breast cancer: the elephant in the bedroom
Beth Prairie, MD, MPH1, Sybil Crawford2, Rakhshanda Layeequr Rahman3, Marjorie
Jenkins4,5. 1Ob/Gyn, University of Pittsburgh, Pittsburgh, PA; 2Preventive and Behavioral
Medicine, University of Massachusetts Medical School, Worcester, MA; 3Surgical
Oncology, Texas Tech University Health Sciences Center School of Medicine, Amarillo,
TX; 4Women’s Health and Gender Specific Medicine, Texas Tech University Health
Sciences Center School of Medicine, Amarillo, TX; 5Laura W. Bush Institute for Women’s
Health, Texas Tech University Health Sciences Center, Amarillo, TX
Objective: Understanding disease-related quality of life (QOL) issues is important for
breast cancer survivors. Women are frequently affected by menopausal symptoms, which
may include vaginal dryness or other sexual function problems, following breast cancer
treatment. Sexual function is an important, but under-recognized, component of survivor
quality of life. We sought to evaluate the impact of sexual function on health-related
quality of life in breast cancer survivors. We hypothesize that poor sexual function will
significantly affect overall quality of life. Design: Women who were known breast cancer
survivors not currently receiving hospital-based treatment were identified in a single
hospital system through chart review. Eligible women were offered participation in a
cross-sectional study to identify significant determinants of QOL in breast cancer
survivors. Informed consent was obtained. Demographic information and detailed
information regarding the women’s breast cancer history and treatment were obtained.
Women were asked to complete the Functional Assessment of Cancer Therapy-Breast
(FACT-B), a self-administered quality of life survey specific to breast cancer survivors in
which higher scores indicate better QOL. Initial analysis indicated that menopausal
symptoms had a significant effect on FACT-B scores, and women were subsequently
asked to complete the Menopausal Rating Scale (MRS), a questionnaire designed to elicit
menopausally-related symptoms in the domains of psychological symptoms,
somatovegetal symptoms, and urogenital symptoms. Higher scores indicate higher
symptom level. Both the FACT-B and MRS contain specific items related to sexual
functioning. Summary statistics, means and standard deviations for continuous variables
and percentages for discrete variables, were used to describe the sample. Spearman
correlations, nonparametric analysis of variance, chi-square test and 2-sample Wilcoxon
were used to evaluate associations between the sexual function variables and BMI, age,
and endocrine treatment. Results: Average age of participants (N=92) was 62.8 years.
The majority had Stage 0 or 1 tumors. Almost 70% underwent endocrine treatment, 67.4%
underwent radiation, 40.2% received chemotherapy, and only 19.6% underwent breast
reconstruction. Average FACT-B score was 113.7, similar to the US population mean of
111.8. The average total score on the MRS was 13.0 (SD=8.2), which is significantly
higher than the general population sample mean of 9.1 (p<0.0001). 60% of women had
either no or only mild sexual problems, while only 17% had severe or very severe sexual
problems. This is in contradistinction to vaginal dryness, where 28% had very severe
symptoms, and 38% had moderate or severe dryness. Vaginal dryness was not significantly
associated with age, BMI, or history of endocrine treatment in this sample. Women had
significantly lower well-being on the sexual function questions on the FACT-B than their
overall scores reflect. 44% were not at all satisfied with their sex lives, and 32% did not
feel sexually attractive at all. BMI was inversely associated with perceived sexual
attractiveness, with women with higher BMIs having lower sexual attractiveness
(p=0.006), but not associated with sexual satisfaction. Conclusion: Breast cancer
survivors in this cohort had high levels of vagina dryness, low levels of sexual satisfaction,
and low levels of feeling sexually attractive. Low scores in these domains reduced their
overall quality of life scores on the two measures used (MRS and FACT-B). Focusing on
overall QOL may miss an import contribution of sexual well-being to long, healthy
survivorship.
P-71.
Effect of a Moderate-to-Vigorous Intensity Exercise Program in Body
Composition and Basal Metabolic Rate of Postmenopausal Women: The
Role of Hormone Therapy
Josiane Rocha1,3, Betania Ogando1,2, Ronaldo Gabriel2, Marco Monteiro2, Helena
Moreira2. 1Physical education, unimontes, montes claros, Brazil; 2Universidade Tras os
Montes e Alto Douro, Vila Real, Portugal; 3Faculdades Integradas Pitagoras, Montes
Claros, Brazil
Objective: – The present study intended to analyse the effect of an exercise program of
step, weight-training and flexibility on the levels of adiposity and on muscle condition of
postmenopausal women, based on the conduction of an investigation with a 12-month
intervention, aiming the influence of hormone therapy (HT). Design: : One hundred sixtynine women (56.80±6.47 years old), 55% with HT, were randomly introduced into an
exercise group (EG, n=91) and a control group (CG, n=78). Height (H) was measured in
anthropometric position, as well as body composition (W, weight, FM, fat mass; FFM, fatfree mass, SM, skeletal muscle mass) and basal metabolic rate (BMR) by using octopolar
bioimpedance (InBody 720). The skeletal muscle mass index was calculated (SMI=
[SM/W] ×100) and the food record method was used. The EG performed a 60-minute
exercise set, three times a week, involving step (50% to 85% heart rate reserve), weight
training (8-10 repetitions at submaximal intensity for two sets) and stretching.The t-test
and analysis of variance (age control) were employed to compare groups. Results: No
differences were found among the averages of the variables in both groups at the
beginning of the study, except for age. In absolute terms the CG revealed (p<0.01) an
increase of FM (1.86%) and a decrease in SM, SMI (-1.06%), FFM and BMR (-27.95
kcal/day). Differences were identified in the percentage of changes of these variables
between the two groups, having these always been more favourable in the EG in relation
to the CG. Height presented a significant increase in EG (0.59 cm, p<0.01). Exercise
influenced (p< 0.01) the variation of H (p=0.03) SM and of SMI (p=0.04), while the HT
affected the variation of the SM (p=0-02), not having an interactive effect been identified
concerning those two factors. In the absence of HT, the EG and the CG revealed
differences (p≤0.01) in the percentage change of the SM. In relation to women that
documented the use of HT, the EG displayed better percentage change of SM, SMI, H and
FFM in relation to those of the CG Conclusion: The research findings suggest that both
attenuation in the loss of muscle mass and improvement of stature in postmenopausal
women take place with possible beneficial effects in posture and functional capacity,
especially in women with HT.
P-72.
Effects of Physical Exercise Programs on Adiposity and Muscle Condition
of Post-Menopausal Women: A Randomized Study
Josiane Rocha1,3, Betania Ogando1,2, Ronaldo Gabriel2, Marco Monteiro2, Helena
Moreira2. 1State University of Montes Claros, Montes Claros, Brazil; 2University of Trásos-Montes and Alto Douro, Vila Real, Portugal; 3Faculdades Integradas Pitagoras, Montes
Claros, Brazil
Objective: analyze the effect of an exercise program on fat mass, visceral fat area (VFA),
skeletal muscle mass (SMM), and skeletal muscle mass index (SMMI) of postmenopausal women. Design: One hundred sixty-nine women (56.80±6.47 years) were
randomized into an exercise group (EG, n=91) and the control group (CG, n=78). The EG
performed 60 minutes of exercise, 3 times a week (step, weight training and flexibility).
Body composition (W, weight; FM, fat mass; FFM, fat-free mass; VFA, visceral fat area;
and SM, skeletal muscle mass) and basal metabolic rate (BMR) were evaluated by using
octopolar bioimpedance before and after a 12-month period. Skeletal muscle mass index
was calculated (SMI= SM/W×100) and the food record method was used. The variable
averages (absolute values and rates of change) were compared by using t-tests and the
degree of statistical significance considered was 5%. Results: In absolute terms, the CG
increased (p <0.01) the FM (1.86%) and the VFA (3.92 cm2). The CG also aggravated the
muscle condition (-1.06%), with adverse reflexes in the BMR (-27.95 kcal /
day).Differences were found (p ≤ 0.05) between the EG and the CG for the Δ% FM (4.23%), ΔVFA (-4.00%), ΔSM (3.09%), ΔSMI (0.03%) and ΔBMR (2.99 %).
Conclusion: The results suggest that the exercise program attenuated the increase in the
levels of total and central adiposity and muscle loss associated with menopause and aging,
conditions that may result in a lower cardiovascular risk and osteoporosis among this
population.
P-73.
Effect of a 12-Month Exercise Program on Body Composition of
Postmenopausal Women: Effects of the Nature of Menopause
Josiane Rocha1,3, Betania Ogando1,2, Ronaldo Gabriel2, Marco Monteiro2, Helena
Moreira2. 1Physical Education, State University of Montes Claros, Montes Claros, Brazil;
2
Sports and Science, Universidade Tras os Montes e Alto Douro, Vila Real, Portugal;
3
Faculdades Integradas Pitagoras, Montes Claros, Brazil
Objective: The aim of this study was to investigate the effect of a 12-month moderateto-vigorous exercise program on body composition of postmenopausal women, analyzing
the influence of the nature of menopause. Design: : A total of 169 postmenopausal women
(aged 40-77 years old) were randomly selected to an exercise (EG, n = 91) or a control
group (CG, n = 78), both with women of induced menopause (27.5% and 26.9%,
respectively) and users of hormone therapy (54.9% and 55.1%). Body composition (W,
weight; FM, fat mass; VFA, visceral fat area; SM, skeletal muscle mass; regional SLM,
soft lean mass arms, trunk and legs) and basal metabolic rate were evaluated by using
octopolar bioimpedance (InBody 720) at baseline after a 12-month period of exercises.
Skeletal muscle mass was calculated by the formula: SMI = SM/W×100 and all the sample
elements completed a 3-day food intake documentation. The EG performed 60 minutes
of exercise, 3 times a week involving step (twice a week, 20 to 25 minutes, 50% to 85%
heart rate reserve), weight training (twice a week, 20 to 25 minutes, 8-10 repetitions at
submaximal intensity for two sets) and stretching (once a week, 45 minutes). The t-test
and analysis of variance (control of age) were employed to compare groups. Results:
There were no statistically significant differences between means of variables in both
groups at baseline except for age. In absolute terms, the CG showed increases (p≤0.01)
of the %FM and of the VFA, as well as a worsening in the muscle condition, being
differences identified (p≤0.05) between them both in what regards rates of changes. The
exercise has influenced (p≤0.04) the variation of the SM, SMI and SLM (p=0.02) in trunk
and legs. The EG showed, as compared to the CG, a better SM, regardless of the NM, and
of the VFA, SMI and SLM at the level of the trunk and lower limbs, in the presence of a
natural menopause. Conclusion: These findings suggest that in healthy postmenopausal
women a 12-month exercise program combining cardiovascular, muscle strength and
flexibility positively influenced body fat distribution and muscular condition, namely
SLM in legs and trunk.
P-74.
The Diabetes Masquerade: Symptoms in Non-Diabetic Postmenopausal
Women
Patricia A. Rouen1, Sarah L. Krein, PhD3, Nancy Reame2. 1McAuley School of Nursing,
Univ of Detroit Mercy, Novi, MI; 2School of Nursing, Columbia University, New York,
NY; 3VA Center for Clinical Management Research, VA Healthcare System, Ann Arbor,
MI
Objective: Women are disproportionately affected by type 2 diabetes mellitus (DM) with
higher lifetime risk of disease incidence and greater severity of complications. Symptoms
of this chronic illness are vague and often not recognized in midlife women. The purpose
of this study is to examine the diabetes symptom experience of postmenopausal women
veterans with and without a DM diagnosis receiving care in the Veterans Affairs (VA)
healthcare system. Design: A comparative group design was used to evaluate diabetes
symptoms in three groups of postmenopausal women veterans (aged 45-60 years): women
without DM (No DM; n=90), women with controlled DM (DM-C; A1c ≤ 7%; n=135)
and women with poorly controlled DM (DM-PC; A1c >7%; n=102). Participants
responded to a national mailed survey on menopause and consented to clinical data access.
Data collected by the self-administered survey included diabetes status, self-care
behaviors and DM symptom assessment. DM symptoms were evaluated with the Diabetes
Symptom Checklist – Revised (DSC-R), a 34-item tool that measures the burden of DMrelated symptoms over the past 4 weeks. A standardized DSC-R global score and eight
symptom subscale scores (hyperglycemia, hypoglycemia, cardiovascular, ophthalmologic,
psychological-fatigue, psychological-cognition, neuropathic-sensation, neuropathic-pain)
were calculated and compared between the groups. Clinical data to characterize the
metabolic state were obtained from VA national laboratory files with consent. Categorical
data were compared by Chi square with Fisher’s exact test; differences in continuous
variables were evaluated by t test and ANOVA with post-hoc analyses. Results: On
average, participants were 55.0 ± 0.2 years of age, obese (body mass index [BMI] 33.9 ±
0.4 kg/m2), and 11.3 ± 0.2 years postmenopause. Women with controlled and poorly
controlled DM were older, of higher BMI and had more co-morbidities than women
without DM. A1c levels were lower in DM-C women (6.4%) compared to those with poor
glucose control (8.9%; p < 0.05). The average age of DM diagnosis was 47.9 ± 0.5 yrs.
Diagnosed at an earlier age (45.4 ± 0.8 yrs vs. 49.8 ± 0.5 yrs; p < 0.001) than their DMC peers, DM-PC women also had the illness longer (10.1 ± 0.7 yrs vs. 5.7 ± 0.5 yrs; p <
0.001). Higher DSC-R global scores (24.5 ± 1.2 vs. 20.2 ± 1.7; p < 0.05) were
demonstrated in women with DM (n=227) compared to those without DM (n=90).
However, seven of the eight DM symptom subscale scores were similar between the
groups; only the hyperglycemia subscale score was higher in women with DM (29.9 ± 1.7
vs. 19.9 ± 2.4, p < 0.05). By ANOVA, DM-PC women had higher DSC-R global scores
compared to their controlled peers and non-diabetic women (DM-PC: 27.8 ± 2.1 vs. DMC: 22.2 ± 1.4 vs. No DM: 20.2 ± 1.7; p < 0.05), while scores between DM-C and
non-diabetic women were similar. Psychological-fatigue symptoms were perceived as the
most burdensome by all participants. There were no differences in subscale scores for
hypoglycemia, psychological-fatigue, psychological-cognition, neuropathic-sensation,
and neuropathic-pain symptoms among the study groups. Hyperglycemia subscale scores
were higher in DM-PC women than those without DM but similar to DM-C women (DMPC: 33.2 ± 2.7 vs. DM-C: 27.5 ± 2.3 vs. No DM: 19.9 ± 2.4; p < 0.05). Greater
ophthalmologic subscale scores were noted in DM-PC women compared to DM-C and
women without DM (DM-PC: 20.0 ± 2.3 vs. DM-C: 13.3 ± 1.6 vs. No DM: 11.7 ± 1.9;
p < 0.05). Cardiovascular subscale scores were higher in DM-PC women compared to
the DM-C group but similar to women without DM. Conclusion: Diabetes related
psychological, neuropathic, hypoglycemic and cardiovascular symptoms are present in
women without a DM diagnosis and perceived to be of similar severity compared to
women with DM. Women with poor glucose control had more burdensome
hyperglycemic, ophthalmologic and cardiovascular symptoms. Symptoms related to
hyperglycemia provided the best assessment of glucose status across the groups. These
data reinforce the need to screen postmenopausal women for type 2 DM. Further studies
are warranted to confirm these findings in non-veteran populations and women of leaner
body size.
P-75.
Overactive bladder in postmenopausal women
Jae hong Sang, Hyoung moo Park. Obstetrics & Gynecology, Chung-Ang University
hospital, Seoul, Republic of Korea
Objective: Recent studies in Korea have shown that the prevalence of overactive bladder
in women over 40 was 18.4%. Overactive bladder syndrome is a urinary urgency, usually
accompanied with frequency and nocturia, with or without urgency urinary incontinence,
in the absence of urinary tract infection or other obvious pathology. This study was
performed to investigate the prevalence of overactive bladder and the effect of hormone
treatment in menopausal women in Korea. Design: The frequency, nocturia, urgency, and
urgency incontinence were examined in menopausal women aged 45 years and older
among patients who visited the Department of Obstetrics and Gynecology, Chung-Ang
University Hospital, between November 2010 and February 2011. Results: Among 350
menopausal women responded to the study, 50 women had urgency, with 14.3% of
prevalence. Among the group with urgency, 28 women showed urgency incontinence,
with 56% frequency. Urgency did not show statistical significance for old age (over 65
years) or the presence of hormone treatment, but showed statistical significance among
the periods of menopause (odds ratio 3.451, 95%CI 1.422-8.377, p=0.004). Also, higher
risks for both frequency (odds ratio 2.921, 95%CI 1.587-5.375, p=0.001) and nocturia
(odds ratio 2.469, 95%CI 1.069-5.702, p=0.037) were observed in the group with urgency
compared to the group without urgency. Conclusion: The results of this study can be
meaningful in studying overactive bladder only in menopausal women for the first time
in the country. Also, older age or hormone treatment did not affect the prevalence of
overactive bladder, and the hormone treatment was not effective in treating the symptoms
of overactive bladder. It is considered that factors affecting overactive bladder in
menopausal women will be understood if further studies with a large number of subjects
on lifestyles and the types of hormones and administration routes are to be performed in
the future.
See table on next page.
59
NAMS11_Regular-LB_Abstracts-2 8/29/11 4:13 PM Page 29
Clinical Poster Presentations (continued)
Incidence of overactive bladder according to menopause duration
Other symptoms in overactive bladder
P-76.
Efficacy of Gabapentin Extended-Release (G-ER) on Vasomotor
Symptoms in Post-Menopausal Women in Breeze 2 Study
Mira Baron, MD1, Verne E. Cowles, PhD2, Wulf Utian, MD, PhD, DSc1, William Koltun,
MD3, Rekha M. Sathyanarayana, MS2, Michael Sweeney, MD2. 1Rapid Medical Research,
Cleveland, OH; 2Product Development, Depomed, Inc, Menlo Park, CA; 3Medical Center
for Clinical Research, San Diego, CA
Objective: To evaluate the efficacy of G-ER 1200mg & 1800mg daily on the frequency
and severity of moderate to severe hot flashes (HF) from baseline to each treatment wk
in post-menopausal women. Design: This was a Phase 3, double-blind, placebo-controlled
study conducted at 45 sites in the US. Post-menopausal women with ≥ 7 moderate to
severe HF per day during the baseline period were randomized to either 1200 mg QD or
1800mg (600mg AM/1200 mg PM) of G-ER or placebo. Additional inclusion criteria
were no history of malignancy within 2 y,and amenorrhea for at least 1 y or amenorrhea
for 6-12 mos with FSH > 40 mIU or ≥ 6 mos post bilateral oophorectomy. Patients were
titrated to their randomized dose over 1 wk. The study medication was taken with a meal
and daily HF & their severity were recorded using an electronic diary throughout the
study. The efficacy measure was the mean change in observed average daily frequency and
severity score of moderate to severe HF from Baseline and to each follow-up week. An
ANCOVA model which included treatment and center factors, and the corresponding
baseline value as the covariate was used to determine the pairwise difference between G
ER and placebo treatments. Results: Out of 565 randomized patients, 559 were included
in the ITT population, 190, 186, & 183 in the 1800mg, 1200mg & placebo groups
respectively, with 148, 149, and 147 subjects, respectively, completing the study through
stable dosing wk 12. The mean (range) age was 53.2 y (28.0 - 70.0), with 66.0% being
Caucasian, 27.5% Black, and 4.7% Hispanic. The mean age at menopause was 44 y (1862) and the mos since the last menstrual period was 109 (1-492). Overall, 49% of subjects
had been amenorrheic for at least 12 mos and 45% had undergone surgical sterilization.
The subjects had an average daily frequency of moderate to severe HF of 12.0 (6.7-41.7),
13.0 (4.43-40.7) and 12.6 (4.9 – 59.6) in the 1800 mg, 1200 mg and placebo groups,
respectively at baseline. Even with a substantial placebo effect, both the 1800mg and
1200mg group had significantly greater reductions in observed average daily frequency
of moderate to severe HF during the titration wk, and at stable dosing wks 1-4 and 8-12.
In addition, the 1200 mg group also had a significant reduction at wk 7 (Figure). The
1800mg group had a significantly greater reduction in observed average daily severity
scores of moderate to severe HF during the titration wk, and at wks 1-5 and wks 7-12. In
contrast, the 1200mg group only had a significant reductions at wks 3, 9, & 12.
Conclusion: The results form this study suggest that G-ER at 1800mg or 1200mg are
similar in their ability to reduce the frequency of HF while the 1800mg dose has a greater
effect on reducing the severity of vasomotor symptoms.
Frequency of Hot Flashes.
60
P-77.
Menstrual Experience and Midlife Symptoms in Puebla, Mexico
Lynnette L. Sievert, PhD1, Elizabeth R. Bertone-Johnson, ScD2. 1Anthropology, UMass
Amherst, Amherst, MA; 2Public Health, UMass Amherst, Amherst, MA
Objective: The purpose of this study was to examine recalled symptom experience before
or during menstrual periods in relation to symptom experience two weeks prior to
interview among 755 women aged 40-60 drawn from a general population in Puebla,
Mexico. Design: Face-to-face interviews lasting 25 to 50 minutes queried if, during the
past two weeks, women experienced one of 22 complaints, including hot flashes and
“sadness or desire to cry.” All women were also asked if they experienced abdominal
cramps during menstruation, and if they had other symptoms during or before their
menstruation. All were prompted with the examples of irritability and “desire to cry.”
Relationships between symptoms associated with menstruation, and between menstrual
and midlife symptoms, were examined by chi-square analyses. Logistic regression was
used to assess whether abdominal cramps and other symptoms associated with
menstruation were determinants of hot flashes at midlife after controlling for relevant
variables. A similar model was used to determine if depression and/or irritability with
menstruation was a determinant of depressed mood at midlife. Results: Fifty-four percent
of women reported cramps during menstruation, 9% reported depressed mood, and 8%
reported irritability before or during menstruation. Women volunteered a range of
symptoms before or during menstruation, including breast tenderness, waist pain (dolor
de cintura), leg pain, headache, GI complaints, and tiredness. Women who reported
depressed mood with menstruation tended to be more likely to report depressed mood in
the past two weeks, and women who volunteered waist pain and abdominal cramping
with menstruation were significantly more likely to report hot flashes. Among women
who had menstruated within the past 12 months (n=279), parity and abdominal cramps
were significant determinants of hot flashes after controlling for education, BMI, and
other potential determinants. Among postmenopausal women (n=418), only “waist pain”
was a significant determinant of hot flashes after controlling for education, BMI, history
of hysterectomy, HT use, and other relevant variables. For depressed mood, current
symptoms of hot flashes, trouble sleeping, and SES were significant determinants of
depressed mood among pre-menopausal women after controlling for education, irritability
with menstruation, depressed mood with menstruation, smoking, parity, and other
potential determinants. Hot flashes and trouble sleeping were also significant determinants
of depressed mood among postmenopausal women. Depressed mood and irritability with
menses were not significant determinants of depressed mood at midlife after controlling
for other variables. Conclusion: Abdominal cramping and hot flashes may both be
associated with drops in levels of steroid hormones. Alternatively, women who experience
and report discomforts associated with menstruation may be more likely to experience and
report discomforts associated with menopause.
P-78.
Bioidentical Hormone Therapy: A Survey of Pharmacists Beliefs
Tasneem Siyam, BScPharm, Nese Yuksel, BScPharm, PharmD. Faculty of Pharmacy and
Pharmaceutical Sciences, University of Alberta, Edmonton, AB, Canada
Objective: In light of the controversy surrounding the term Bioidentical Hormone
Therapy (BHT), health care providers may provide information to patients based on their
personal beliefs with BHT. The objective of our study was to assess pharmacists’ belief
on the definition, as well as safety and efficacy of BHT and determine potential factors
influencing these beliefs. Design: This was a cross-sectional survey design. Community
pharmacists in Edmonton, Alberta and surrounding areas were asked to participate in a
written, self-administered survey. A 32-item questionnaire was created with sections on
demographics, beliefs on BHT definition, efficacy and safety information sources, and
comfort level with BHT. Summary and inferential t test statistics were used for analysis.
Approval was received by the University of Alberta Health Ethics Research Board.
Results: One hundred and thirty four pharmacists were approached for participation in
the survey and 95 pharmacists completed the questionnaire (71% response rate).
Respondents were mostly female (65%) and less than 30 years (33%). Fifteen percent
worked in a pharmacy that compounded BHT. Majority of pharmacists believed hormone
therapy (HT) had a role in treating vasomotor symptoms and vaginal dryness (96%and
92% respectively), but only 51% believed HT prevented factures. Forty one percent of the
respondents believed BHT included only compounded hormones. Over half (54%)
believed BHT to be equally effective as other HT for vasomotor symptoms. Similarly,
54% believed BHT to have equal effects on CVD, VTE and breast cancer risk, while 29%
believed BHT to have lower risk of side effects. Furthermore, 39% of pharmacists believed
that natural progesterone cream could be used to prevent endometrial hyperplasia.
Pharmacists who worked in compounding pharmacies were more likely to believe in less
risk of BHT compared to other HT (p<0.05, use of natural progesterone cream to prevent
endometrial hyperplasia (p=0.001) and the use of saliva testing in BHT dosing (p<0.05)
as compared to pharmacists who worked in other settings. Similarly, BHT compounding
pharmacists were more confident recommending and providing patient education on BHT
(p<0.05). Conclusion: Community pharmacists had varying beliefs with BHT and these
beliefs were strongly influenced by practice setting. This study helps identify areas for
targeted education.
P-79.
LibiGel® (Testosterone Gel) Safety Study Completes Enrollment and
Continues With a Low CV Event Rate
Michael C. Snabes, M.D.1, Scott Berry2, Joanne G. Zborowski1, Deborah Grady, M.D.3,
William White, M.D.4. 1BioSante Pharmaceuticals, Inc., Lincolnshire, IL; 2Berry
Consultants, College Station, TX; 3University of California, San Francisco, CA;
4
Cardiology Center, University of Connecticut School of Medicine, Farmington, CT
Objective: LibiGel® is in Phase III development for treatment of postmenopausal women
with Hypoactive Sexual Desire Disorder (HSDD). FDA approval requires demonstration
of long-term cardiovascular (CV) and breast safety. Herein we report on study progress.
The objective of the study is to establish the safety of LibiGel treatment of
postmenopausal women. Design: This is a Phase III, randomized, double-blind, placebocontrolled, multi-center CV events-driven, adaptive design comparison of daily LibiGel®
testosterone gel verses identical placebo gel in postmenopausal women with HSDD and
CV risk. Design of the study incorporated enrollment completion prior to the maximum
of 4,000 subjects if the unblinded, independent Data Monitoring Committee (DMC)
statistician calculated the predictive probability of study success to be > 90% after
continuing the study for an additional 12 months after enrollment completion using
prospectively designed Bayesian modeling of the distribution of endpoint CV events. The
primary safety outcome measure is the effect of treatment on the incidence of a composite
of adjudicated CV events. Results: Based on the results of the adaptive design sample size
algorithm, enrollment was completed at 3,656 randomized subjects. In addition, the DMC
has recommended that the study continue as planned after each of the 6 separate unblinded
data evaluations. The mean age of subjects at randomization is 58.6 years: two thirds are
hypertensive, 65% dyslipidemic, 21% smokers and 20% diabetic. More than 4,000
subject-years of exposure already have been accrued. The rate of adjudicated, protocolmandated CV events of subjects is 0.58% and the breast cancer rate is 0.24%. Conclusion:
The LibiGel safety study continues to accrue event and other safety data and is blinded
to all except the DMC. Even with an enhanced-risk patient population, the CV event rate
remains quite low. Successful completion of the LibiGel clinical program could result in
the first approved pharmacologic therapy for women with HSDD. Sponsor: BioSante
Pharmaceuticals, Lincolnshire, Il.
P-80.
Effects of Quetiapine Extended-Release on Sleep and Quality of Life in
Midlife Women With Major Depressive Disorder
Benicio N. Frey, MD, PhD2, Erika Haber2, Gustavo C. Mendes3, Meir Steiner1, Claudio
N. Soares, MD, PhD, FRCPC1. 1Psychiatry and Behavioural Neurosciences, Obstetrics @
Gynecology, McMaster University, Hamilton, ON, Canada; 2Psychiatry and Behavioural
Neurosciences, McMaster University, Hamilton, ON, Canada; 3Psychiatry, Sao Paulo
Federal University, Sao Paulo, Brazil
Objective: Existing data support a heightened risk for the development of depression in
perimenopausal and early postmenopausal women. Depression during this “window of
risk” is commonly associated with other complaints, including vasomotor symptoms,
sleep disturbances and other conditions that adversely impact wellbeing and overall
quality of life measures. Quetiapine extended-release (XR) has been shown to alleviate
mood symptoms and improve sleep parameters in individuals with unipolar and bipolar
depression. Recent preliminary data also support antidepressant properties of quetiapine
XR for the treatment of symptomatic, depressed midlife women. To date, no studies have
examined the effects of quetiapine XR on sleep and quality of life in peri/postmenopausal
women with major depressive disorder (MDD). Design: Forty peri- and postmenopausal
women (defined by STRAW criteria), ages 40-60 years and meeting criteria for MDD
were enrolled into a clinical trial that included a 2-week, placebo lead-in phase; those
who remained significantly depressed after completion of the placebo lead-in phase then
entered an 8-week open trial with quetiapine XR, flexible dose, 150-300 mg/day.
Depressive symptoms were measured with Montgomery-Asberg Depression Rating Scale
(MADRS). Sleep parameters and quality of life were assessed using the Pittsburgh
Insomnia Rating Scale (PIRS) and the Menopause-Specific Quality of Life Questionnaire
(Meno-Qol), respectively. Results: Twenty-three subjects were eligible for the modified
intent-to-treat, last observation carried forward analyses (i.e., those who had at least one
follow-up assessment while receiving treatment with quetiapine XR). Results of these
analyses revealed significant sleep improvement with quetiapine XR based on PIRS
domains of subjective sleep distress, overall sleep parameters and sleep-related quality of
life (p<0.001 for all comparisons). Moreover, quetiapine XR led to a significant
improvement in all Meno-Qol domains (i.e. vasomotor, physical, sexual and
psychological; p<0.05 for all comparisons). Lastly, global improvement in sleep
parameters (changes in total PIRS scores) was strongly correlated with improvement in
depressive symptoms (changes in total MADRS scores) (rS=0.79; p<0.001). Conclusion:
Treatment with quetiapine XR may not only alleviate depressive and menopause-related
symptoms but also lead to significant improvement in sleep and subjective quality of life
in peri- and postmenopausal women with MDD. Further, larger studies should confirm the
efficacy and tolerability of quetiapine XR for the management of the depression in this
population.
P-81.
Antidepressant Effects on Brain Activation During the Emotional Conflict
Task in Perimenopausal Women: a Functional MRI Study
Luciano Minuzzi, MD, Ph.D, Benicio N. Frey, Geoffrey B. Hall, Ivan Skelin, Stefanie
Attard, Meir Steiner, Claudio N. Soares, MD, PhD, FRCPC. Department of Psychiatry and
Behavioural Neurosciences, McMaster University, Hamilton, ON, Canada
Objective: Neuroimaging studies have identified brain regions involved with emotional
conflict and emotional resolution. In a previous functional magnetic resonance imaging
(fMRI) study, we have demonstrated that peri/postmenopausal women present a distinct
brain network for emotional regulation using an Emotional Conflict task. Despite the
menopausal transition being associated with a higher risk for the development of Major
Depressive Disorders (MDD), little is known about the impact of MDD and its treatment
on the emotional regulatory circuit in midlife women. In this study we evaluated the brain
correlates of emotional regulation in peri- and postmenopausal women before and after
antidepressant treatment and in age-matched controls. Design: Nine peri/postmenopausal
women (mean age = 52.2 ± 4.3 years) diagnosed with MDD and 18 healthy age-matched
controls (mean age=51.7 ± 5.5 years) underwent 3T fMRI scanning while performing the
Emotional Conflict task (Etkin et al., 2006). After a 2-week placebo lead-in phase, placebo
non-responders received 8 weeks of treatment with SNRIs (Duloxetine 60-120 mg/day or
Desvenlafaxine, 50 mg/day). fMRI scanning was performed at baseline and after 8 weeks
in treated participants and matched controls. Brain activation was contrasted according to
the emotional conflict resolution paradigm (high conflict resolution > low conflict
resolution) using BrainVoyager QX software. Results: Unmedicated MDD patients
presented deactivation of dorsolateral prefrontal cortex (DLPFC) during the emotional
conflict resolution. Age-matched controls showed deactivation in a number of cortical
regions including DLPFC, rostral anterior cingulate, and temporal regions. After eight
weeks of antidepressant treatment, MDD patients showed clinical improvement (mean
total MADRS scores = 5.9 ± 5.8, p<0.05). Compared to baseline, healthy controls did
not present any changes in brain activation during the Emotional Conflict task whereas
treated MDD participants showed increased activation of DLPFC. Conclusion: These
novel but preliminary fMRI findings suggest that MDD in perimenopause and early
postmenopause might be associated with changes in the network involved in emotional
regulation. Compared to healthy volunteers, untreated subjects with MDD failed to
deactivate a number of brain regions in response to the paradigm. After receiving
treatment, MDD patients showed activation of DLPFC, a brain region that was deactivated
under the same emotional test pre-treatment. The distinct active brain area after
antidepressant treatment might indicate neuroplasticity due to treatment or compensatory
effect against the disease. Future studies should investigate the impact of hormone
variations on these cortical networks in this population.
P-82.
A Pooled Analysis of the Effect of Desvenlafaxine on Sleep in Women With
Vasomotor Symptoms Associated With Menopause
Claudio N. Soares1, Howard M. Kravitz2, Ru-fong J. Cheng3, Rana Fayyad3, Dale Grothe3,
Christine J. Guico-Pabia, MD, MBA, MPH3. 1McMaster University, Hamilton, ON,
Canada; 2Rush University Medical Center, Chicago, IL; 3Pfizer Inc, Collegeville, PA
Objective: Desvenlafaxine (administered as desvenlafaxine succinate) reduces the
number and severity of hot flushes in women with moderate to severe vasomotor
symptoms (VMS) associated with menopause. Desvenlafaxine 100 mg/d was
demonstrated to be the lowest effective dose for moderate to severe VMS. An exploratory
analysis of the effect of desvenlafaxine 100 mg/d on sleep was carried out using pooled
data from 5 multicenter, double-blind, randomized, placebo-controlled trials of
desvenlafaxine efficacy and safety for VMS. Design: Postmenopausal women seeking
treatment for VMS were randomly assigned to receive desvenlafaxine (50 mg/d–200
mg/d) or placebo in 5 trials; all 5 studies included a desvenlafaxine 100-mg arm. Data
from women treated with desvenlafaxine 100 mg/d or placebo were pooled for analysis.
Entry criteria for all 5 studies included ≥7 moderate to severe hot flushes per day or ≥50
per week at baseline. One study had additional inclusion criteria requiring a Greene
Climactic Scale (GCS) total score ≥12 and hot flush item score ≥2 at baseline. Study
durations were 12 weeks (2 studies), 26 weeks (1 study) or 52 weeks (2 studies). The
primary endpoint of interest was change from baseline in the number of nighttime
awakenings due to hot flushes at week 12 and across the 12-week time period (pooled
from 3 studies with these data). Number of nighttime awakenings was analyzed using a
mixed-effects model for repeated measures, with treatment, baseline, and study in the
model and week the repeating factor, as well as using last observation carried forward
(LOCF). Secondary exploratory measures included change from baseline to week 12 for
GCS sleep item score (difficulty in sleeping; 3 studies) and score at week 12 on
Menopause Symptoms Treatment Satisfaction Questionnaire (MS-TSQ), item 3
(satisfaction with effect of treatment on sleep; 2 studies). The incidence of selected sleeprelated treatment-emergent adverse events (TEAEs) was determined for pooled data from
all 5 studies. Results: A total of 3323 women took at least 1 dose of desvenlafaxine 100
mg (n=1711) or placebo (n=1612) and were included in the safety population for this
analysis. Nighttime awakenings data were available for 881 women from 3 studies, 475
treated with desvenlafaxine 100 mg/d and 406 treated with placebo. Mean number of
nighttime awakenings at baseline was 3.56 for the desvenlafaxine group and 3.34 for
placebo. Women treated with desvenlafaxine achieved an adjusted mean (± standard error)
reduction of 2.22 ± 0.07 awakenings due to hot flushes per night at 12 weeks with a mean
reduction of 2.06 ± 0.06 per night across 12 weeks of treatment; significantly greater than
the reductions of 1.65 ± 0.08 and 1.47 ± 0.06 awakenings due to hot flushes per night for
women treated with placebo (P<0.001). Difficulty sleeping was significantly reduced in
desvenlafaxine-treated women compared with placebo; adjusted mean decrease in GCS
sleep item score at week 12 of 0.79 ± 0.04, from a baseline mean of 1.87, compared with
61
Clinical Poster Presentations (continued)
a reduction of 0.56 ± 0.04 for placebo (baseline = 1.83; P<0.001), respectively. At week
12, 66% of women treated with desvenlafaxine and 44% of women treated with placebo
reported that they were “satisfied” or “extremely satisfied” with the effect of treatment on
sleep (P<0.001). The most common selected sleep-related TEAEs (reported by ≥5%
desvenlafaxine-treated women in the safety population and at least twice the placebo rate)
were fatigue (9.2%; placebo, 3.3%) and somnolence (6.8%; placebo, 1.2%). Conclusion:
In women with moderate to severe VMS, Desvenlafaxine 100 mg/d significantly reduced
the number of nighttime awakenings due to hot flushes, reduced reported difficulty
sleeping, and led to reports of greater treatment satisfaction compared with placebo.
P-83.
Quality Of Life Questionnaires: Translation and Linguistic Adaptation
from English into Traditional Chinese
Lily Stojanovska, PhD1, Cindy Law, RN2, Christopher Haines, PhD2. 1School of
Biomedical and Health Sciences, Victoria University, Melbourne, VIC, Australia;
2
Department of Obstetrics and Gynaecology, The Prince of Wales Hospital, Chinese
University of Hong Kong,, Hong Kong, Hong Kong
Objective: The Women’s Health Questionnaire (WHQ) and the Utian Quality Of Life
(UQoL) are reliable and valid instruments designed to measure the quality of life (QOL)
among English-speaking climacteric women. To describe the translation and cultural
adaptation of the UQOL and the WHQ for the Chinese postmenopausal women from
Hong Kong Design: The English version of the UQOL and the WHQ were translated into
Chinese and cross-culturally adapted to the Chinese from Hong Kong environment,
according to standard internationally recommended methodology of translation. This
process involved several steps: (a) forward translation; (b) reconciliation; (c) back
translation into Chinese and its review, followed by (d) harmonization. The adapted
version from each scale was administered to thirty postmenopausal women with the
purpose of assessing the level of comprehension and cognitive equivalence of this version.
A full validation study involving over 100 participants is currently underway. Permission
to use the instruments by the original authors was obtained. Results: The translated
version of both scales was straightforward. In the cognitive debriefing, results were
analyzed and incorporated in the report, showing that all the questions were adequately
understood by more than 88% of the women interviewed. Despite of this, the viability of
the instrument and the difficulties mentioned by the volunteers were analyzed by a five
member committee, and logical, fluent, conceptual and experiential equivalences were
obtained. Conclusion: The present study fulfills an important step in the process of
translation and cultural adaptation of the UQOL and the WHQ scales, leading to its
subsequent validation and utilization in clinical practice and scientific research in Hong
Kong and mainland China. This methodology can serve as a model for translation of
UQOL and the WHQ into other languages.
P-84.
The use of Maca (Lepidium meyenii) on plasma glucose and cytokine
patterns in postmenopausal Hong Kong Chinese women
Lily Stojanovska, PhD1, Kristina Nelson, BSc1, Vasso Apostolopoulos, PhD2, Stephanie
Day, PhD2. 1School of Biomedical and Health Sciences, Victoria University, Melbourne,
VIC, Australia; 2Department of Immunology, Macfarlane Burnet Institute for Medical
Research, Melbourne, VIC, Australia
Objective: Maca is a nutritious plant used historically as a therapeutic compound in
alleviating symptoms of menopause transition. Whilst Macas’ mechanism of action is
unknown limited studies indicate that it is not directly correlated with hormonal changes.
Complex interactions between endocrine and immune systems are emerging in menopause
physiology, in particular altered cytokine profiles and inflammation with decreasing
oestrogen levels. The aim of this study is to determine the effects of supplemental Maca
during a 12-week double-blind cross-over trial, on selected biological markers (Th1/Th2
cytokines) and plasma glucose in post-menopausal Chinese women Design: Twentyseven healthy postmenopausal women were recruited in a randomised, double-blind,
placebo-controlled crossover trial. Women received 3.3g/day of Maca and matching
placebo for six weeks each. At baseline, 6 and 12 weeks, blood was taken for
measurements of plasma cytokines (IL-2, IL-4, IL-5, IL-10, IL-12 (p70), IL-13, GMCSF, IFN-λ and TNF-α) as well as plasma glucose. Results: Three analytes (IL-5, IL-10
and IL-13) were detectable within range, whilst six analytes (IL-2, IL-4, IL-12, GM-CSF,
IFN-λ, TNF-α) were found to be in concentrations beyond detectable range. Overall,
there was minimal variation in detectable cytokines between baseline, placebo and Maca
(p>0.05). The mean fasting plasma glucose was marginally but not significantly elevated
in both placebo and Maca treatments when compared to baseline (p>0.05). Conclusion:
Maca does not alter cytokine markers nor plasma glucose levels in Chinese
postmenopausal women. This is not unexpected given the healthy menopausal cohort
studied. In addition we only measured nine cytokines, which may not capture the complex
interactions within an extensive cytokine network. Further studies are required in a larger
cohort, for a longer duration and larger cytokine panel in to explore Maca’s effect in
menopause.
62
P-85.
Results from 2010 NAMS Survey on Secondary Transfer of Transdermal
Estrogen Preparations
Cynthia A. Stuenkel, MD1, Margery Gass, MD2. 1Medicine, Endocrinology and
Metabolism, University of California, San Diego, La Jolla, CA; 2The North American
Menopause Society, Mayfield Heights, OH
Objective: As the use of transdermal estrogen preparations has increased, inadvertent
transfer of cutaneous estrogen from women to pets and children has rarely been reported
and is unfamiliar to most clinicians. In the summer of 2010, the Veterinary Information
Network, a subscription online resource for veterinarians, compiled nearly 50 reports of
cats and dogs presenting with signs and symptoms of estrogen excess linked to use of
cutaneous estrogens, primarily compounded preparations, by their owners. Concurrently,
the Food and Drug Administration issued a safety communication based on 8 cases of
estrogen excess in children and 2 in pets resulting from transfer of estrogen from women
using Evamist, an FDA approved estrogen preparation. This report reflects the responses
of the attendees at the 2010 Annual Meeting of The North American Menopause Society
to questions about their experience with transfer of transdermal estrogen preparations to
children or pets. Design: At the time of registration, a brief survey was distributed to all
attendees of the 2010 Annual Meeting of The North American Menopause Society
(NAMS). The questions included the following: Do you know of a child or pet affected
by secondary estrogen exposure? If ‘Yes’ to the child query, then describe the approximate
age of child and signs of hormone effect. If ‘Yes” to the pet query, please describe the pet
and signs of hormone effect. For either child or pet, please describe the nature of hormone
exposure (which hormone products and how/where they were being used). The
questionnaire also asked: Did you submit FDA Form 3500 (persons) or 1932a (pets) to
report the findings? Results: Of 1,299 attendees, 576 were clinicians; 312 attendees
completed the survey (24% of the total in attendance, 54% of clinicians). Among the
respondents, 98% indicated they did not know a child or pet affected by secondary
estrogen exposure; 7 attendees (2% of responders) indicated they knew of affected
children (n=1) or pets (n=6). The child was between ages of 10 and 12 years and presented
with early signs of puberty. Estrogen cream had been used by the child’s mother. Of the
6 pets that were reported, 5 were described as ‘small dogs.’ The 6th animal was not
described. Gynecomastia, enlarged/darkened nipples, or breast development was reported
in 4 of the 6 pets. One dog also experienced a loss of chest hair; another was
“sick/lethargic.” In 2 dogs, the veterinarian documented elevated serum
estrogen/progesterone levels. Among the 6 pets reported, 4 were exposed to Evamist
(applied to forearm in one case and abdomen in another), one was exposed to Estrogel
(applied to forearm), and 1 was exposed to compounded estradiol cream and compounded
10% progesterone cream (applied to forearm). FDA reporting had been completed for
one pet by the veterinarian; no other cases were reported. In summary, one clinician out
of 50 who attended the NAMS Annual Meeting and completed the questionnaire had
observed secondary transfer of transdermal estrogen from patients to pets or children. In
the experience of NAMS clinicians, 5/6 pet exposures followed use by the owner of FDA
approved transdermal therapies: Evamist and Estrogel. One of the pets and the only child
reported were exposed to compounded hormone therapy. Conclusion: The results of the
survey indicate that among clinicians seeing menopausal women, cases of secondary
transfer of transdermal estrogen preparations may be more common than anticipated from
pre-marketing safety studies. These findings underscore the importance of educating
patients about appropriate hygiene measures to avoid transfer of estrogen to children and
pets when using any cutaneous estrogen preparations. Should findings of breast
enlargement in children or nipple or vulvar enlargement in pets occur, promptly
communicate to the pediatrician or the veterinarian the possibility of secondary transfer
of estrogen.
P-86.
Construction and Validation of an instrument that breaks the silence: The
impact of domestic and/or sexual violence on womens health as shown
during climactery
Sandra D. Teixeira de Araujo Moraes, MD, Ph.D., Angela Maggio da Fonseca, MD, Ph.D,
José M. Soares Júnior, MD, Ph.D, Vicente R. Bagnoli, MD, Ph.D, Marilena A. Sousa,
MD, Wilson Maça Yuki Ariê, MD, Ph.D, Edmund Chada Baracat, MD, Ph.D. Ginecology,
University of São Paulo, São Paulo, Brazil
Objective: construction and validation of a questionnaire able not only to measure the
consequences of domestic and/or sexual violence on womens health at climactery but
also to break the silence of these women. Design: application of a questionnaire at the
Outpatient Clinic Climactery of the General Hospital - University of São Paulo (FMUSP),
Brazil, performed during 2009 for 124 women aged between 40 and 65 years, who were
victims of domestic and/or sexual violence, distributed in three groups: 1. Violence
exclusively during childhood/adolescence; 2. During adulthood; 3. Throughout all phases.
The instrument encompasses 34 items evaluating: 1. Place of residence and who the
woman lives with; 2. Start, frequency and type of violence; 3. Search for health assistance
and report of the violence; 4. Violence and number of comorbidities; 5. Violence and
Menopausal Kupperman Index (IMK). Results: The instrument presented Cronbach
Alpha=0.82, reliability among examiners (+0,80), and good possibility to be reproduced.
Average menopause age -45,4 years in average, in the control Group (GC) it was 48,1
years and average BMI (Body Mass Index) 28,5 (±2,8), similar to the GC, but frequent
violence during adulthood showed a BMI of 30,0 (±2,8).Women subjected to violence
during childhood/adolescence presented an average of 5,1 comorbidities during adulthood,
4,6 and 4,4 for both phases. Sexual violence (43,5%) and other types of violence both
present average comorbidities (4,60) but represent a significative impairment of sexual
life. For those submitted to domestic and/or sexual violence we find: osteoporosis 85,5%;
depression/psychiatric disorders 69,4%; hypertension 54%; rheumatic diseases and
diseases of the joints 47,7%; allergies 37,9%; fibromyalgia 33,1%; varicose veins in the
legs 29,8%; Labyrintitis 29,8%; diabetes 15,3%; disk hernia 14,5%; uterine/ovarian/breast
cancer 13,7%, in which braet neoplasies represents 47,05% of these cancers; other
cancers: 2,4%. Regarding the intensity of climacteric symptoms, 53,2% of the women
present moderate IK moderado, 25,8% light IK e 21% serious IK. Higher percentages of
serious Kupperman Index (IK) were observed in women submitted to violence in both life
phases (29,3%), moderate IK in childhood/adolescence (75%) and during adulthood light
IK (33%). There were significative associations between suffering any type of violence
during all phases of their lives, sexual violence during any phase of their lives and a serious
IMK. Among those women, 80,6% did not search health services due to the violence
suffered. Number of comorbidities and Kuperman Index are not associated to tobacco
use (Mann-Whitney test). Among the diverse violence episodes suffered by women, the
ones that most impair their physical and psychological health was the category “Having
been hit/suffered because of a man who is the father of my child” (38,7%), followed by
“Suffering many traumas/violence by someone who raised or adopted me” (33,1%),
“Suffering humiliation, verbal abuse, calumnies…” (25%), “Having been hit/suffering
because of someone I loved or still love” (24,2%), and “Having been abused/raped by
someone close to me and/or from my family” (17,7%). Regarding the actions of health
professionals approaching violence, 75% of the women say they would have asked for
help if the professional had brought the theme during the consultation and 17,7% said
they would not tell the violence they were subjected to, even if they were questioned about
it. These women suggested that: 58,1% “professionals must open spaces for people to
talk, they must give us more security”, 20,2% “Professionals must stimulate women to not
accept violence and to report violence”. Violence suffered had a negative influence on
the way of living and acting for 90,3% of the women in these study. Conclusion: The
questionnaire presents good internal consistency and a validated construction, can be
easily reproduced and is indicated to evaluate the consequences of domestic and/or sexual
violence on womens health during climactery.
P-87.
Life quality in women victims of gender vilence during climactery
Eli M. Moraes, Sandra D. Teixeira de Araujo Moraes, MD, Ph.D., Angela Maggio da
Fonseca, MD, Ph.D, Vicente R. Bagnoli, MD, Ph.D, Josefina O. Polak Massabki, Jucilene
Sales da Paixão, Pérsio Yvon Adri Cezarino, Edmund Chada Baracat, MD, Ph.D.
Ginecology, University of São Paulo, São Paulo, Brazil
Objective: Characterizing a group of women in climactery who were victims of gender
violence by information level, depression and quality of live, verifying the results of a
psychological intervention on these subjects. Design: Subjects were 62 women aged
between 40 and 60 years. A psychological intervention was developed, and a group
context, with the objective to inform about climacteric syndrome, supporting and
psychologically preparing the patients. Intervention comprised 12 weekly encounters of
1h30 hours each. In order to render easier the discussion and the experience of the
proposed themes (definition of climactery and menopause, sexuality, post trauma stress,
familiar and amorous relationships) we employed group dynamic techniques. Participants,
at the start and at the end of the intervention, were evaluating to assess their information
level, anxiety, depression and life quality. Instruments employed were: Beck Depression
Inventory, Instrument for Evaluation of Life Quality (WHOQOL-Bref) and a
questionnaire, designed by the researcher, on knowledge about climactery, menopause,
sexuality and healthy habits. Results: At the first evaluation of the knowledge
questionnaire, questions regarding climactery, menopause and sexuality presented the
higher percentages of incorrect answers. On questions about the consequences of violence
on women’s health, analyzed during the climactery phase, most of the participants state
they would have told health professionals, during consultation, about the violence
suffered, if they had been approached in a more humane way. In the first evaluation of
depression, participants presented alteration in their moods (disphoria). Regarding quality
of life, in the evaluation previous to the intervention, scores presented by the participants,
when compared to the normative study, were lower in psychological and social aspects.
Comparison of the evaluation results previous and posterior to the intervention, shows
that, in the knowledge questionnaire, there was significative increase in the percentage of
adequate answers, in questions dealing with the difference between climactery and
menopause, concepts of climactery and menopause, purpose of the hormonal reposition
therapy, beauty and sensuality during climactery. Final evaluation signaled a reduction in
the average of anxiety when compared to the first application, which may indicate a
contribution of the intervention to this result. Regarding depression, average reduction of
scores shows that, after the intervention, patients fit into the category with no depression.
Conclusion: From these results it is possible to conclude that interventions designed to
approach the violence suffered, to inform and to prepare women to live climactery is an
intervention that may contribute to improve their life quality.
P-88.
Social Determinants of Domestic Violence Among Women During
Climactery
Sandra D. Teixeira de Araujo Moraes, MD, Ph.D., Angela Maggio da Fonseca, MD, Ph.D,
Vicente R. Bagnoli, MD, Ph.D, Eli M. Moraes, Eliana Guimarães Labes, Érica Mendonça
das Neves, Edmund Chada Baracat, MD, Ph.D. Ginecology, University of São Paulo, São
Paulo, Brazil
Objective: Analyzing social determinants interacting in the lives of climacteric women
subjected to domestic and/or sexual violence. Design: Descriptive exploratory study with
qualitative approach including 124 women aged between 40 to 65 years, victims of
domestic violence, profiting from their weekly therapeutic group encounters, in the ECOS
Space of the University Hospital (Hospital das Clínicas) of the Medicine College of the
University of São Paulo, between August and December, 2010. Before this psychological
intervention in a group context, we applied a semi structures questionnaire, self appliable,
with epidemiological data and the major social determinants acting on the lives of these
women. Average age was 55,8 years (± 6), menarcha 13 years (± 2), first sexual
intercourse 19,4 years (± 5,5), menopause 45,4 years (± 6,3 ). During the period in which
they suffered violence, 68% lived in the urban region. Answers to the open questions were
grouped by subject similarity (Minayo, 2004) Results: Type of violence suffered during
any phase of life: Physical (75,8%), Sexual (59,75), Psychological (59,3%), Physical
Neglect (75,8%), Emotional Neglect (31,41%). Women suffering sexual violence (59,7%)
report most of the episodes occurring during childhood/adolescence. Regarding the
violence they suffered, 88,0% was perpetrated by an intimate partner, and was most
frequent during 20 to 29 years of age. White women (56%) have more difficulties to relate
violence suffered, contrary to afro-descendents (43,58%) and Orientals (3,84%). There
was no significative relationship between skin color or income and having suffered
domestic and/or sexual violence, but having more than 11 years of schooling was a
protective factor. There was a significant relationship between domestic violence and use
of alcohol and/or other drugs by the victimizer. Among the many types of domestic
violence it is possible to outline: demeaning the woman, menaces to deprive the child
from basic needs, menaces of aggression or death and privation of freedom, unleashing
diverse degrees of anxiety. Unmarried women or women who are separated, as well as
those living alone present higher spanking rates than married women. Psychological
violence is more frequent among married women. Reproductive health: no children
3,85%, one child 15,75%, two children 28,29%, three children 21,54 %, four children
17,04 %, five or more children 13,50% of the women: never had an abortion 53,37%, one
abortion 24,11%, two abortions 12,54%, three abortions 3,21%, four abortions 3,53%,
five or more abortions 3,21%. Women having active sexual life amounted to 28,3% and,
among these, only 7,87% consider it to be satisfactory. Smokers are 15,0% and 3,1% are
alcohol users. Women with higher schooling look for health assistance (especially
psychotherapy or psychiatric services) and for the police more often, while those who
have less schooling (less than 8 years of schooling) look for the hospital only when
suffering major physical hazards, like fractures, bleeding and pain that does not respond
to regular medicine. Women who did not look for health services when suffering violence
amounted to 80,6% of the sample and, when they looked for these services, due to other
reasons, they would have told about the violence if the health professional had questioned
or if the consultation was more humane. Those who did not look for the police explain
they do not trust the efficiency of the service, mentioning a degree of gender violence by
the teams offering this kind of assistance. Conclusion: This study renders evident
breeches in women’s health attention in which professionals lost the opportunity to break
the cycle of violence and also shows the importance of assistance humanization, in which
“caring” includes a way to live, to be and to express oneself. In the individual
psychotherapy it is possible to suppose women who are victims of sexual violence during
their childhood tend to choose inadequate intimate partners, repeating the violence in
their lives. This may be due to factors such as a combination of beliefs, negative
expectations, misadjusted behaviors, low self esteem, lack of self-protective techniques
and the cultural approach that renders violence as banal, regarding abuse as a normal
experience.
P-89.
The State of the Breast Cancer Vaccine
Kristi Tough, MD, Holly Thacker. Cleveland Clinic, Cleveland, OH
Objective: To survey the literature on the state of clinical advancement of prophylactic
and adjuvant breast cancer vaccinations. Developments in immunotherapy, our aging
population and the growing prevalence of cancer make cancer vaccination a leading edge
of clinical research. Design: Literature review was conducted via PubMed search for
phase II trials of breast cancer vaccines. Search terms used were: human, breast cancer
vaccine and phase II trial. The reference lists from selected articles were searched for
relevant contributions to breast cancer vaccine research. The National Cancer Institute
website was reviewed for ongoing clinical trials. Results: No prophylactic or therapeutic
vaccine exists for breast cancer which affects 1 in 8 women by aged 90 or 12% of the
general population, with higher incidences in BRCA patients and kills 40,000 women
yearly. Despite the absence of an approved breast cancer vaccine, there is no dearth of
animal and human research, particularly on various adjuvant vaccines used in the
metastatic setting. The first FDA approved autologous vaccine was the prostate cancer
vaccine (sipuleucel-T or Provenge®) which confers survival benefit of 4.5 months for
men who failed hormonal therapy. Synergy of immunotherapy and modalities of
chemotherapy or hormonal therapy is also employed in breast cancer vaccine research.
Four delivery systems are currently being widely studied for effective vaccination which
include: dendritic cell, viral, peptide and whole cell based vaccines. Published phase II
trials exist for peptide and viral vaccines. Peptide vaccines stimulate T cell and antibody
cascade against tumor cells expressing the same antigenic protein (mostly HER2 proteins).
Published results of 177 metastatic or locally advanced breast cancer patients with E75
vaccination showed disease free survival advantage of 85% in immunized patients (24/29
patients) and 59% in the placebo arm after 22 month follow up and recurrence rate 8%
verses 21% respectively (P<0.19). A larger follow up trial showed waning immunity after
6 months post vaccination but in vivo T cell response and clinical recurrence rate are not
always linearly related. Recent data on 48 month follow up revealed decrease recurrence
rate after 6 months of E75 vaccination (NeuVax®) with booster compared with control.
A phase III trial, Prevention of Recurrence in Early Stage, Node Positive Breast Cancer
with Low to Intermediate HER2 Expression with NeuVax® Treatment is planned for
2012. Viral based vaccines are another vaccination strategy that show promise for clinical
relevance. Placement of antigens (mucin 1) within a virus or plasmid vector naturally
elicits an immune response. Mucin 1 (MUC 1) is an ideal target for its over-expression
in breast tumors, glycosolated membrane and strong immunogenicity. Phase I/II clinical
trials showed the vaccine Sailyl-Tn- keyhole limpet hemocyanin (STn-KLH) or
63
Clinical Poster Presentations (continued)
Theratope® (a synthetic antigen that mimics mucin expression) conferred positive
humoral response and significant survival benefit (19.1 months vs 9.2 months, p=0.001)
in vaccine versus control groups respectively. Unfortunately phase III trials showed no
impact on overall survival or time to progression in1030 women. New research with both
MUC1 and carcinoembryonic antigen (CEA) genes placed into poxviruses are ongoing.
The idea of a prophylactic vaccine is not novel, but begets complex issues of
autoimmunity. Pre-clinical work with alpha- lactalbumin (a self protein expressed in the
breast) shows vaccination provides robust T cell mediated immune response and
protection from tumor growth in transgenic mice. This is promising evidence that primary
prevention with vaccination may stave of breast cancer. Clinical trials with alpha
lactalbumin are pending. References: Will be provided on poster presentation if abstract
provided. Conclusion: Breast cancer vaccination research has exciting advancements in
immunology and oncology, however we lack evidence of benefit in clinical trials.
Promising phase II clinical trials show that vaccination with peptide based HER2, E75
provided survival benefit and decreased recurrence. Thus far, most vaccinations
complement the myriad of treatments for advanced breast cancer. A prophylactic breast
cancer vaccination is still in preclinical years, but hopefully the thriving research milieu
will eradicate this prevalent cancer in women.
P-90.
Distribution of 24 hours urinary equol excretion as an indicator for the
physiological range in healthy Japanese equol excretors
Shigeto Uchiyama1, Atsuko Onoda1, Tomomi Ueno1, Belinda H. Jenks2, Soh Iwashita1,2,
James Brooks2, Yoshiko Ishimi3. 1Otsuka Pharmaceutical Co.,Ltd., Saga, Japan;
2
Pharmavite LLC, Northrige, CA; 3National Institute of Health and Nutrition, Tokyo,
Japan
Objective: Soy bean, which is a traditional food in the Asian countries, is consumed more
in Asia compared to the Western countries. The difference in soy consumption between
Asia and Western is involved in the health status in each area. Previous studies showed that
the incidence of breast and prostate cancers is much lower in Asian than in the Western
population, which might suggest that intake of soy relates to the reducing risk of those
cancers in Asian countries. Soy isoflavones (daidzein, genistein and glycitein) have been
reported to prevent the hormone-related cancers, although people still have not a few
concerns of their estrogenic effects. Equol is a metabolite of the soy isoflavone daidzein,
which was produced by intestinal bacteria, then equol may be involved in the prevalence
of these types of cancer as well as soy isoflavones. The frequency of equol producers is
approximately 30% in Western population while approximately 50% in Japanese. Tiny
and ignorable amount of equol is existed in the limited foods (i.e. milk and egg yolk).
Thus, only produced amount of equol from daidzein in the body can affect the amount of
equol exposure. To date, only a few studies have been reported in terms of the produced
amount of equol in Japanese. Therefore, this study was developed to understand the levels
and potential benefits for a safety and effective amount of equol exposure in healthy
Japanese adults. Data of the 24h urinary excretion of equol was evaluated as potential
scientific data point for evidence regarding the typical daily dose of exposure. So, we
could know daily physiological range of equol exposure in healthy Japanese adults.
Design: 13 epidemiological studies, 1,345 subjects (545 men, 492 premenopausal women,
and 308 postmenopausal women) participated, were conducted from 1996 to 2010. All
subjects had no current or past history of serious illness. A questionnaire survey was used
to confirm the health and menopause status. The 24h urine of the participants was
collected under the conditions of their normal daily life (no restrictions of soy foods).
Alcohol intake was prohibited during the 24h urine collection. The urine samples were
enzymatically deconjugated, and daidzein, genistein, and equol were measured by high
performance liquid chromatography (HPLC). The 24h urinary excretions of the
isoflavones and equol were determined using the values measured by HPLC. If the
subjects had equol levels that were above the detection limit (0.27 nmol/mL), they were
defined as equol excretors. All studies were performed with the approval of the human
studies institutional review board for each participating institution. Results: The
frequency of equol excretors was 36.3% among men, 33.3% among premenopausal
women, and 52.6% among postmenopausal women. The total number of equol excretors
was 524, then the minimum amount of 24h urinary excretion of equol was 0.4 μmol/day
(0.1 mg/day), the maximum was 318.0 μmol/day (77.0 mg/day), the 50th percentile was
12.5 μmol/day (3.0 mg/day), and the 95th percentile was 119.2 μmol/day (28.9 mg/day).
For equol, daidzein and genistein, premenopausal women had significantly lower values
than men or postmenopausal women (equol; P<0.001, daidzein: P<0.001, and genistein:
P<0.001 versus men or postmenopausal women, respectively). The 24h urinary excretion
of equol in postmenopausal women was significantly higher than that of men (P=0.004),
but there were no differences for daidzein or genistein between these groups. Conclusion:
The results of the present study showed that the 24h urinary equol excretion was 0.1-77.0
mg/day in the equol excretors. This range would be physiological exposure of equol in
healthy Japanese population. These results could help understand to determine a safety
and effective levels of equol exposure in a body.
P-91.
The effects of natural S-equol supplementation on skin aging in
postmenopausal women: A pilot randomized placebo-controlled trial
Tomomi Ueno1, Atsuko Onoda1, Shigeto Uchiyama1, Belinda H. Jenks2, Soh Iwashita1,2,
James Brooks2, Takeshi Aso3, Kayoko Matsunaga4. 1Otsuka Pharmaceutical Co.,Ltd.,
Saga, Japan; 2Pharmavite LLC, Northrige, CA; 3Tokyo Medical and Dental University,
Tokyo, Japan; 4Fujita Health University School of Medicine, Aichi, Japan
Objective: A factor of skin aging in postmenopausal women is loss of estrogen.
Approximately 30% of dermal collagen is diminished during the first 5 years after
menopause. Some studies have shown that hormone therapy increases collagen content,
64
elasticity, thickness and hydration in skin, while reducing the wrinkles in postmenopausal
women. Soy isoflavones (daidzein, genistein and glycitein) have similar structures to
estrogen and exhibit estrogenic activity by binding to estrogen receptors. Equol, which is
an active metabolite of daidzein, can be produced in approximately 50% of the Japanese
and 20–30% of the US population after consumption of soy. The ability to produce equol
depends on the presence of certain intestinal microorganism. We recently isolated and
identified a lactic acid bacterium, Lactococcus 20-92, that metabolizes daidzein to Sequol. Using this strain, we successfully produced a fermented soy food containing natural
S-equol. Clinical studies have shown the beneficial effects of natural S-equol supplement
on menopausal symptoms and bone metabolism in postmenopausal Japanese women.
However, the efficacy of oral intake of S-equol on skin aging in humans is unknown. In
the present study, we investigated the effects of natural S-equol on the skin aging in
Japanese postmenopausal women. Design: The study was conducted with a doubleblinded, randomized, placebo-controlled design. Healthy postmenopausal women aged
45-65 years, who were equol non-producers, were recruited for the study. The women
were less than 5 years since the onset of menopause One hundred and one subjects were
divided into three groups, namely, EQL10 group (n =34, 10mg of equol/d), EQL30 group
(n = 33, 30mg of equol/d), and placebo group (n = 34, 0mg of equol/d). Placebo or natural
S-equol supplement were orally ingested twice a day for 12 weeks. Skin parameters of
crow’s feet wrinkles (area and depth), hydration, transepidermal water loss (TEWL) and
elasticity were measured at baseline, 4, 8, and 12 weeks during treatment. Blood
biochemical and endocrinological (sex and thyroid hormones) tests were carried out at the
same time as skin parameters measurements. For the assessment of reproductive organs
(uterus) and breasts safety of natural S-equol supplement, vaginal cytodiagnosis,
endometrial thickness and mammography were performed before and after treatment.
Results: No statistically significant difference was observed at baseline values of wrinkle
area and maximum largest wrinkle depth between groups. Wrinkle area in the EQL30
group was significantly lower compared to or vs. the placebo group at 12 weeks. The
wrinkle areas in both the EQL10 and EQL30 groups were significantly decreased over the
treatment period (P = 0.029 and P = 0.004, respectively). The maximum largest wrinkle
depth was significantly lower in EQL30 group compared to placebo group at 4 (P = 0.002)
and 12 weeks (P = 0.015). In addition, the change in maximum largest wrinkle depth over
the treatment period was significantly different between EQL30 and placebo group (P =
0.001). Both of the area and maximum largest depth in wrinkle showed a dose-dependent
improvement by natural S-equol supplementation (P = 0.001 and P = 0.017, respectively).
No statistically significant differences were observed in skin hydration, TEWL or skin
elasticity among the groups. There are no serious gynecological adverse events on uterine
or breast tissues, and no significant effects on hormone status during consumption of
natural S-equol for 10 or 30 mg/day. Conclusion: Oral administration of 10 mg and 30
mg S-equol/day for 12 weeks improved crow’s feet wrinkles in equol non-producing
Japanese menopausal women without serious adverse events. The data of this study
suggest that natural S-equol supplementation has potential to improve quality of life for
postmenopausal women by slowing the skin aging. Findings from this current study
warrant further investigation in a longer treatment period, different ethnicities and
statistically powered study.
P-92.
Characteristics of Patients attending a Dedicated Premature Ovarian
Failure (POF) Clinic
Maria Velasco1,3, Taryn Becker2,3, Kelsey E. Mills, H.BSc, MD1,3, Wendy L. Wolfman,
MD, FRCSC1,3. 1Department of Obstetrics and Gynaecology, Mount Sinai Hospital,
Toronto, ON, Canada; 2Division of Endocrinology and Metabolism, Women,s College
Hospital, Toronto, ON, Canada; 3University of Toronto, Toronto, ON, Canada
Objective: The clinical characteristics of patients presenting with POF seem to be
evolving, with an increasing proportion of patients having POF secondary to cancer
therapies. The objective of the study is to describe the clinical characteristics of the
patients attending a dedicated POF Clinic. Design: We conducted a retrospective study
of patients evaluated at the POF clinic at Mount Sinai, Toronto, Canada, from January
2008 to March 2011. A chart review was performed to collect the following data:
demographics, etiology, hormonal therapy and bone mineral density (BMD) scores.
Descriptive data is presented as median and standard deviation or percentage. BMD was
measured using dual-energy x-ray absorptiometry or DXA. BMD was considered low
when the Z-score was -2.0 or lower. Data were compared using Chi square tests for
categorical variables and Student’s t-test for continuous variables. Results: 179 patients
attended the POF clinic during the study period, and the data was available for 172 of the
patients. 144 women were included in the analysis, as the remainder did not have POF.
The remainder of women were perimenopausal, had normal cycles, had hypothalamic or
pituitary amenorrhea or had polycystic ovary syndrome. The mean age was 27.7 years.
The etiology of POF was unknown in 74 (51%) of women seen in our clinic. 39 women
(27%) had received cancer therapy either as a combination of chemotherapy and radiation
(n=21), chemotherapy alone (n=13), bilateral salpingoophorectomy (n=4) and radiation
alone in 1 patient. Of the group that had POF of unknown etiology, 25 (33%) had evidence
of autoimmunity as demonstrated by the presence of thyroid antibodies, hypothyroidism
and/or other autoimmune disease. The patients with unknown etiology presented at an
older age than the patients with POF secondary to therapy for cancer (29.9+/-8 and 22.8+/8.9 years, p<0.001). 27 patients presented with primary amenorrhea (19%), 9 of them
secondary to cancer therapy. Thirteen women had Turner’s syndrome (9%), and 4 had
Fragile X premutation (3%). Of the total group, 85% (n=122) were receiving estrogen
therapy, 67 (47%) with the oral contraceptive pill (OCP) and 55 (38%) with hormone
therapy (HT), while 22 (15%) declined therapy. 18% used vaginal estrogens although
they were taking OCP or HT. Twelve patients (8%) had pregnancy after diagnosis, with
egg donation in 10 women and spontaneous pregnancy in 2 patients. Conclusion: This
study demonstrates that the most common etiology for POF patients is still unknown. Of
this group, one third showed evidence of autoimmunity. One hypothesis is that the
etiology could be autoimmune oophoritis on this subgroup. The second most common
etiology of POF is cancer therapy, with the combination of chemotherapy and radiation
as the treatment that most frequently produces POF. One third of patients presenting with
primary amenorrhea are cancer survivors, thus studies focused on preserving ovarian
function on young patients are needed. Most of the patients in our study are receiving
hormonal therapy in the form of an oral contraceptive or hormone therapy, to minimize
morbidities associated with long-term estrogen deprivation.
P-93.
Incidence of Low Bone Density in Patients Presenting to a Premature
Ovarian Failure (POF) Clinic
Maria Velasco1,3, Taryn Becker2,3, Wendy L. Wolfman, MD, FRCSC1,3. 1Department of
Obstetrics and Gynaecology, Mount Sinai Hospital, Toronto, ON, Canada; 2Division of
Endocrinology and Metabolism, Women,s College Hospital, Toronto, ON, Canada;
3
University of Toronto, Toronto, ON, Canada
Objective: Women with untreated POF may have increased morbidity, particularly from
bone fractures and cardiac disease. For these reasons they are treated with estrogen
therapy, either with an oral contraceptive (OCP) or hormone therapy (HT). Currently,
there is no consensus on which regimen is better. The objective of this study is to evaluate
baseline bone mineral density (BMD) in patients presenting to a premature ovarian failure
clinic. Other objective is to evaluate the relationship between type of estrogen therapy
and age. Design: This was a retrospective study of patients evaluated at a dedicated POF
clinic at Mount Sinai Hospital, Toronto, Canada, from January 2008 to March 2011. After
establishing the need for estrogen replacement, patients are given the option of OCP or
HT. A chart review was conducted to extract the following data: age at presentation,
etiology of POF, estrogen replacement therapy and BMD. Descriptive data is presented
as median and standard deviation or percentage. BMD was measured using dual-energy
x-ray absorptiometry or DXA. BMD was considered to be low when the Z-score was -2.0
or lower. Data was compared using Chi square tests for categorical variables and MannWhitney U test was used for continuous variables. Results: 179 women were seen at the
POF clinic during the study period. 144 women included in the analysis, as the remainder
did not have POF. Mean age was 27.7 (+/- 9.6) years. The etiology of POF was unknown
in 74 patients (51%), secondary to therapy for cancer in 39 (27%), Turner syndrome in
13 (9%), Fragile X Premutation in 4 (3%) and other etiologies in 14 patients (10%). Of
the total group, 85% were receiving estrogen therapy, 47% in the form of an OCP and 38%
were receiving HT. The age of patients taking an OCP was significantly lower than the
age of patients taking HT (22.5 +/- 9.19 versus 29.3 +/- 8.19 years, p < 0.001). BMD was
available for 78 patients at presentation (54%), with 28 (36%) presenting with low BMD.
We did not find a difference between BMD and age of diagnosis (p=0.59). Conclusion:
In this series, the majority of women with POF are receiving estrogen therapy, with
younger patients preferring OCPs and older patients choosing HT. More than one third
have low BMD at presentation, suggesting either longstanding hypoestrogenemia or other
factors as etiologies for low bone density. Further studies are required to evaluate if there
is a longer-term impact of type of estrogen therapy (OCP vs. HT) and BMD.
P-94.
Effect of Baseline Body Weight on the Efficacy of Desvenlafaxine for
Vasomotor Symptoms Associated with Menopause
Michelle Warren1, Ru-fong J. Cheng2, Weihang Bao3, Michael J. Louie3, Christine J.
Guico-Pabia, MD, MBA, MPH2. 1Columbia University Medical Center, New York, NY;
2
Pfizer Inc, Collegeville, PA; 3Pfizer Inc, New York, NY
Objective: High body weight or body mass index (BMI) and weight gain are associated
with increased reporting of hot flushes (HFs) in the menopausal transition. Desvenlafaxine
(administered as desvenlafaxine succinate) at the 100-mg dose has demonstrated efficacy
for the treatment of moderate to severe vasomotor symptoms associated with
menopause.The objective of this analysis was to examine effect of baseline body weight
or BMI on the efficacy of desvenlafaxine 100 mg/d for treating moderate to severe HFs
in pooled data from 4 double-blind, randomized, placebo-controlled trials. Design: Data
from 4 similarly designed studies assessing the effect of desvenlafaxine on number and
severity of HFs were pooled for this analysis. Postmenopausal women experiencing ≥7
moderate to severe HF/d (or ≥50/wk) and with BMI ≤40 kg/m2 (3 studies) or ≤34 kg/m2
(fourth study) were randomly assigned to receive desvenlafaxine (50 mg/d to 200 mg/d)
or placebo in the 4 trials; all 4 trials included a desvenlafaxine 100-mg arm. Study
durations were 12 (1 study), 26 (1 study), or 52 weeks (2 studies). The percentages of
women classified as normal (BMI<25 kg/m2), overweight (BMI 25 to <30 kg/m2), or
obese (BMI≥30 kg/m2) at baseline were determined. To assess the association between
baseline weight or BMI and efficacy at weeks 4 and 12, analysis of covariance (ANCOVA)
was used with change in number and severity of HFs as the dependent variables.
Independent variables included treatment, study, and baseline weight or weight category
(normal, overweight, or obese). Treatment by weight interaction was examined in the
same model by adding the interaction term. Results: A total of 661 women treated with
desvenlafaxine 100 mg/d and 588 with placebo were included in the analysis. Mean
weight at baseline was 72 kg for each group; 37.6% of participants were overweight at
baseline and 26.6% were obese. Regardless of baseline weight, women on desvenlafaxine
100 mg/d had a larger reduction in number of HFs than women on placebo (P<0.001). The
treatment effect was more apparent in non-obese women. The treatment by baseline
weight and treatment by weight category interactions were significant at week 12 (P=
0.033, and 0.021). The reduction from baseline in number of moderate and severe HFs was
similar for desvenlafaxine-treated women of different weight categories, but heavier
women appeared to have a larger response to placebo (Figure). A similar pattern of results
was observed for HF severity. Conclusion: Normal and obese women treated with
desvenlafaxine achieved similar reductions in HFs. However, among women treated with
placebo, obese women had greater HF reduction compared with women with normal BMI
at week 12.
P-95.
Development of a Multidisciplinary Comprehensive Women’s Midlife
Assessment Clinic
Catherine J. Wheeler, MD, Angela Deneris, CNM, Ph.D., Shanna M. Salmon, BS.
Ob/Gyn, University of Utah Health Sciences Center, Salt Lake City, UT
Objective: To develop and evaluate satisfaction with a multidisciplinary, comprehensive
health assessment clinic for midlife women ages 40-65, and to provide in one setting:
health education to promote wellness and early disease identification, age-appropriate
evidence-based screening, multidisciplinary evaluation and risk assessment, a
personalized health plan, and coordination of additional care. Design: According to the
Office on Women’s Health, Utah ranks 47th or below in key health indices pertinent to
women, including Pap smear screening, cholesterol screening, mammograms, and routine
check-ups. A potential factor in accessing healthcare is inconvenience, and not having
enough time. In one response to this, the University of Utah and its Center of Excellence
in Women’s Health (COE) developed a multidisciplinary comprehensive women’s midlife
assessment clinic. A steering committee comprised of, primary care and specialty
providers and representative administrators, identified current women’s health services at
the University of Utah campus, learned about midlife women’s health programs at other
COE sites, and commissioned a survey of local women to measure an interest in a
comprehensive wellness center and to identify the most important specialties and services
to include. The steering committee reviewed guidelines and literature to identify evidencebased recommendations for age-appropriate routine health screens in women. Consecutive
midlife women attending two gynecology clinics over a two week period were surveyed
about health issues of concern to them. A comprehensive questionnaire to assess health
and risk behaviors was developed. The clinic model was developed to include: 1. Preclinic preparation: Participants completed the questionnaire which was reviewed by clinic
staff. Based on responses, appropriate health screens were recommended, which, with
the exception of colonoscopy and pap smear, were completed before the clinic visit. The
clinic staff developed a visit plan for each participant based on each participant’s goal for
the clinic, her current health habits and conditions, risk factors, and abnormal results from
the pre-clinical testing. 2. Three clinic components: shared education, individual
assessment, and wellness coaching. Each clinic began with a two hour education session
during which experts discussed memory, heart health, stress reduction, menopause, and
intimacy (issues identified by women as their top concerns). Next, each participant had a
thorough health assessment from providers specializing in primary care, and gynecology,
as well as full skin cancer screen by dermatology, and hearing assessment. Participants
consulted with a health coach regarding an area of their life they are working to improve.
3. After the visit, participants received a complete summary of their visit, results of testing,
and a personalized health plan, which was also forwarded to their primary providers for
continuity of care. Additional recommended testing and/or referrals were also coordinated.
5. About two weeks after the clinic, every participant was surveyed by phone. Immediately
after the clinic, all providers were surveyed. This information was used to improve
subsequent clinics. Results: Four Women’s Midlife Assessment Clinics were held
between November 2009 and February 2011. There were 6 to 12 women in each clinic.
Commercial insurance reimbursed most of the cost of this care, with participants paying
copays and a small fee for the education component. Post clinic surveys revealed
participants were uniformly satisfied with their experience and the thoroughness of the
clinic. Among the most valuable aspects were: seeing multiple providers in the same visit;
time to address all concerns and questions; discussing results during the clinic; and the
education. Conclusion: The development of this innovative multidisciplinary and
comprehensive clinic provides convenient, same-day access to a variety of healthcare
professionals, and information specific to women. Participants were highly satisfied with
the model.
P-96.
Capturing Undiagnosed Health Problems in a Multidisciplinary
Comprehensive Women’s Midlife Assessment Clinic: A Pilot Study
Catherine J. Wheeler, MD, Angela Deneris, CNM, Ph.D., Shanna M. Salmon, BS.
Ob/Gyn, University of Utah Health Sciences Center, Salt Lake City, UT
Objective: To evaluate the health risks, symptoms, and behaviors in women who attended
four pilot Women’s Midlife Assessment Clinics held between November 2009 and
February 2011 at the University of Utah. Design: As women age they tend to experience
chronic health problems, but many do not adequately access healthcare. The University
of Utah developed a comprehensive multidisciplinary Women’s Midlife Assessment
Clinic, including education, assessments by primary care, gynecology, dermatology,
audiology, and consultation with a health coach. The model included pre-clinic
preparation. Participants completed a comprehensive questionnaire and evidence-based
testing in advance, and the assessment team developed a visit plan. Four pilot clinics were
held from November 2009 to February 2011, with 6 to 12 women attending each consult
clinic. During quality assurance reviews, several trends were noted, highlighting
opportunities for early identification of illness and symptoms, which may improve with
intervention. Results: A total of 34 women participated in the clinics. Most participants
were employees at the University of Utah, all from an urban setting, 31 were Caucasian,
and 3 were of Asian descent. The mean age of these women was 52 years; all were high
school graduates with 19 women having post graduate degrees. All of the women had
medical insurance. Fifteen women were pre-menopausal and nineteen were postmenopausal. Most of these women (29) had a primary care or gynecology provider, and
26 of them had been seen by their providers within the last 2 years; 27 had never had an
65
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Clinical Poster Presentations (continued)
audiology exam (79%), and 13 had never had a dermatology evaluation (38%), Problems
identified included risk factors for heart disease, and under-treatment for depression or
anxiety. More than half of the women (53%) had past or current risk factors for heart
disease including: hypertension, abnormal lipids, or diabetes mellitus. Fourteen of the
women (41%) had a body mass index (BMI) of 30 or above, and 13 (38%) had waist
circumference (WC) of greater than 35, also risk factors for heart disease. Of the 34
women, 29 (85%) had a family history of heart disease, including hypertension, abnormal
lipids, diabetes, heart attack, heart failure, and sudden death. Excluding BMI and WC as
risk factors, 33 of the 34 women (97%) had a personal and/or family history risk for heart
disease. Twenty-one of the women carried a diagnosis of depression (62%), with 10 of
them currently on medication; yet 13 of these women (62% of those being treated)
indicated current symptoms of depression, consistent with inadequate treatment. Seven
women (21%) did not carry a diagnosis of depression, but had symptoms diagnostic for
depression. Despite 76% of participants having had preventive care within 2 years, a new
diagnosis was identified in 25 of the 34 participants (73%). Previously undiagnosed health
problems identified in the clinic included: melanoma (1), cardiomegaly (1), breast mass
(1), cervical polyp (2), osteopenia (4), abnormal lipids (9), pre-diabetes with a fasting
glucose >110 (1), heart murmur (2),eczema (1), abnormal TSH (2),vitamin D deficiency
(7), vitamin D insufficiency (6). Conclusion: Although the 34 women who participated
in the pilot clinics were educated, insured, and 3/4 had received preventive services within
2 years, the clinic identified a significant number of health problems that needed to be
addressed. Possible explanations include: 1. Completion of a thorough questionnaire prior
to the clinic; 2. Testing performed prior to the clinic; 3. Pre-clinic visit planning, including
identifying positive health and habits, identifying risks for intervention, positive review
of systems for evaluation, and abnormal results; 4. Adequate time with providers to allow
for thorough assessments and to review risk factors and symptoms; 5. Participants also
prepared for the visit in advance, which allowed them to be clear on what they wanted to
accomplish at the clinic, their goals, and their concerns. This unique health care model has
the potential to improve health care for women in midlife by allowing early diagnosis of
disease, improvement of symptoms, wellness and prevention counseling, education,
improved lifestyle, and early intervention.
and total plasma antioxidant status [TAS] using Randox Laboratories, Ltd kits; ED was
determined using Zung’s depression scale. The tests were carried out at the beginning
and at 6 months of treatment. An alternative cut-off value of LPO ≥0.320 μmol/L was
defined on the basis of the 90th percentile of young healthy subjects. Results:
Lipoperoxides levels were significantly higher in HT and P groups than PRE women (HT
0.348±0.05 and P 0.358±0.05 vs. 0.310±0.03 μmol/L, p<0.001) and antioxidant markers
were low in POS. LPO levels decreased after 6 months in HT group (0.309±0.07 μmol/L,
p<0.05); GPx increased (71.2±18 U/gHb, p<0.01); in PRE and P groups were similar to
basal. We found 9 (28%) women in PRE, 10 (31%) in HT and 9 (24%) in P, with ED in
basal time, and the POS women with ED had high LPO levels. After 6 mo. decreased
women with distress in HT group (6 [18%], p<0.05), and LPO also diminished in this
group (Figure). Conclusion: Our findings suggest that HT decreases OS and emotional
distress in posmenopausal women. This work was supported by grant DGAPA-UNAM
IN302809 and sponsored by Laboratorios Senosiain SA de CV. Trial registration:
COF000120.
P-97.
The Impact of Severity of VMS on Health Status, Resource Use and
Productivity
Jennifer Whiteley, Ed.D, MSc., M.A.1, Jan-Samuel Wagner2, Andrew Bushmakin1, Lewis
Kopenhafer2, Jill Racketa1. 1Health Economics, Pfizer Inc, New York, NY; 2Kantar Health,
New York, NY
Objective: The current study characterizes health-related quality of life (HRQoL), work
productivity, and resource use among post-menopausal women by severity of vasomotor
(VMS) symptoms. Design: Participants were selected from the 2010 US National Health
and Wellness Survey which is a cross-sectional, internet-based survey representative of the
adult US population. Women age 40-75 years, who did not report a history of menstrual
bleeding or spotting for one year, were considered post-menopausal and eligible for
analysis (N=3,267). Cohorts of women with no (n=1740), mild (n=931), moderate
(n=462), and severe (n=134) vasomotor symptoms (VMS) were compared, controlling
for demographic and health characteristics. Outcomes measures included health status
(EQ-5D), work productivity (WPAI) within the past 7-days, and healthcare resource use
within the past 6-months and were assessed using linear models Results: The mean age
(SD) for women experiencing severe VMS was 57.92 years (7.84), 58.76 (7.64) for
moderate VMS, 60.47 (7.35) for mild VMS, and 64.46 (7.12) for women not experiencing
VMS. After controlling for demographic and health characteristics, women experiencing
severe and moderate VMS reported significantly lower mean health status scores
compared to women with no symptoms (severe=0.77, moderate=0.82, mild=0.85,
none=0.86; p<.0001). In addition, the mean number of menopause symptom-related
physician visits was significantly greater among women with severe, moderate or mild
symptoms compared to women with no symptoms (severe=2.73, moderate=2.37,
mild=1.63, none=0.724; p<.0001). Among employed women experiencing VMS, women
with severe and moderate symptoms had adjusted presenteeism (percent impairment while
working due to a problem) of 24.28% and 14.3% compared to 4.33% in women with mild
symptoms (p<.001), and activities of daily living impairment of 31.66% and 17.06%
compared to 6.16% for women with mild symptoms (p<.0001). Conclusion: Among
post-menopausal women, those reporting greater severity of VMS symptoms was
significantly associated with lower levels of health status and work productivity, and
greater healthcare resource utilization.
P-98.
Antioxidant effect of hormone therapy on oxidative stress and emotional
distress in posmenopausal women
Mariano Zacarias-Flores, MD ObGyn1, Martha Sánchez-Rodríguez, PhD2, Alicia ArronteRosales, M Sc2, Víctor Manuel Mendoza-Núñez, PhD2. 1Hospital Gustavo Baz Prada,
Instituto de Salud del Estado de México, Nezahualcoyotl, Edo. México, Mexico; 2Facultad
de Estudios Superiores Zaragoza, Unidad de Investigación en Gerontología, UNAM,
México, DF, Mexico
Objective: To determine the effect of hormone therapy (HT) on oxidative stress (OS) and
emotional distress (ED) in postmenopausal women (POS). Design: A randomized, double
blind controlled trial was carried out in 100 women: 1) control, 33 premenopausal [PRE]
(46±3.7 years, estradiol (E2) 102.0±67 pg/mL, FSH 10±7 pg/mL); 2) HT (0.625 mg/d of
synthetic conjugated estrogens [Sixdin®] plus 5 mg/10d of medroxiprogesterone [MPA]),
33 POS (52±3 years, E2 20±4 pg/mL, FSH 55±21 pg/mL); 3) placebo [P], 34 POS (53±3
years, E2 21±3 pg/mL, FSH 53±22 pg/mL). We measured lipoperoxides [LPO] by
TBARS assay, erythrocyte superoxide dismutase [SOD], glutathione peroxidase [GPx]
66
Figure. Lipoperoxides levels in premenopausal, and postmenopausal women with
hormone therapy or placebo, with and without ED, basal and after 6 months.
*Repeated measures ANOVA, p<0.001).
P-99.
Results from the 2010 Insomnia Related to Menopause Survey
Jacqueline Zummo, MS, MPH, MBA, Todd Grinnell, William Spalding, Randall
Marshall. CRMA, Sunovion Pharmaceuticals, Inc., Marlborough, MA
Objective: Research suggests that 40-50% of women report difficulty sleeping during
menopausal transition.1,2 A survey in women 40-65 years of age evaluated trouble
sleeping/insomnia during the transition. Design: Manhattan Research administered an
online, 27-question, multiple-choice survey between 7/16/10-7/22/10 to women ages 4065. Eligible respondents self-identified as peri-menopausal or post-menopausal, and
reported “trouble sleeping/insomnia” during menopause (N=927). The questionnaire
assessed the impact of sleep disturbances on quality of life (QoL), daily function,
interactions with healthcare professionals (HCPs), and experience with insomnia
treatments. Results: The most common complaints were trouble staying asleep (79%),
tiredness/fatigue during the day (67%), and trouble falling asleep (63%). 75% reported
insomnia during menopause having moderate-high impact on QoL and daily function and
56% reported a negative impact on relationships. More than half (53%) had seen their
HCP within the last 6 months, only 38% of whom discussed difficulty sleeping/insomnia.
This discussion was rarely initiated by the HCP (8%). About 1/3 (31%) of respondents had
been prescribed a sleep-aid, and 77% felt it was helpful. At the time of the survey, 55%
of respondents prescribed a sleep-aid were still taking one, and most (93%) planned to
continue treatment. Conclusion: In the eligible population, sleep disturbances during
menopause impacted daily function, relationships, and quality of life, with trouble staying
asleep identified as the most common sleep problem. Less than half of sufferers discussed
sleep issues with their HCP, and almost entirely at their own initiative. Insomnia during
menopausal transition may be frequently under-recognized and undertreated by HCPs.
References: 1. Shaver J.L. Women and sleep. Nurs Clin North Am. 2002;37:707-718. 2.
Soares, C.N. Insomnia in women: an overlooked epidemic? Arch Women Ment Health.
2005; 8: 205-213.
Disclosure Statement
The North American Menopause Society (NAMS) is a provider
of continuing medical education (CME) accredited by the
Accreditation Council for Continuing Medical Education
(ACCME) and is committed to:
• A
ligning the content of educational activities with the
interests of learners
Following the review of disclosure forms, the Society may find
that a faculty member has a conflict of interest. This does not
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equiring disclosure forms from those being
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prior to the activity
Discussion of Investigational
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NAMS requests that faculty identify any investigational
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an off-label use is discussed, please refer to the official
prescribing information for approved indications,
contraindications, and warnings.
67
Key to Disclosures
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Abbott
Agile
Allergan
American Institute of Ultrasound in Medicine
Amgen
Archives of Women’s Mental Health
Arkochim
Arkopharma
Ascend
Astellas
Astra Zeneca
Azur
Bayer
Bionovo Inc.
BioSante Pharmaceuticals, Inc.
Boehringer-Ingelheim Pharmaceuticals
Canadian Institute of Health Research
Chemo
Cleveland Clinic Foundation Innovations Center
Climacteric
Columbus Center for Women’s Health Research
Cook Ob/Gyn
Corcept
Daiichi-Sankyo
Depomed Inc.
Duramed/Barr
EDP Technologies
Eli Lilly and Company
Endoceutics
Enzymatic Therapies
Fabre-Kramer
Faith Care, Inc.
Ferring
Forest Laboratories
Foundation for Osteoporosis Research & Education
Genentech
Gilead
GlaxoSmithKline
Hamilton Community Foundation
Healthywomen.org
Hormone Foundation of The Endocrine Society
Hygeia/Orcas Therapeutics
Journal of Women’s Health
Johnson & Johnson
KV Pharma
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Lupin
Medical Diagnostic Laboratories
Meditrina
Menopause
Merck
Merrion
NAMS
National Alliance for Research on Schizophrenia and Depression
National Institute of Mental Health
National Institute on Aging
National Institutes of Health
NDA Partners
New England Research Institutes
Novartis Pharmaceuticals Corporation
Noven
Novogyne
Novo Nordisk
NYU School of Medicine Alumni Corporation
OBG Management
Own The Bone Advisory Board
Pfizer, Inc
Pharmavite Inc.
Philips Ultrasound
Physicians Service Incorporated
Procter & Gamble
QuatRx
Roche
Rowpar
sanofi-aventis
Schaper & Brummer GmbH & Co. KG
Se-cure Pharmaceuticals
Semprea Labs
Servier
Shionogi
Solvay
SonoSite, Inc.
Sunovion Pharmaceuticals, Inc.
Teva Women’s Health
University of Virginia
Upsher-Smith Laboratories
Warner Chilcott
Watson
Wyeth
Yoplait
Disclosures
Name
Board of Consultant/ Directors/
Advisory Stock/
Trustees Employment
Board
Shareholder
Abraham, L
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67
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Al Omari, W
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Aldrighi, J
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Appt, S
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Archer, D
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1, 2, 13, 18, 23, 51,
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67, 87, 88
Arias, R
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13, 63, 67, 84
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Avis, N
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Bachmann, G
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10, 16, 26, 44, •
51, 60, 63, 67, 71, 81
Benson, H
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Bohuslav, J
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Broekmans, F
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51
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Brown, J
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Caico, C
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Carpenter, J
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Choi, H
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Christianson, M
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Crandall, C
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Cray, L
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Dasen, S
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84
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Davis, S
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15, 87
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Del Pup, L
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Doyle, C
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Drogos, L
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Duke, C
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Elavsky, S
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Ensrud, K
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Fisher, W
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Freedman, M
•
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84
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Freedman, R
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Freeman, E
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Gass, M
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Gerber, L
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Gibson, C
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Goldstein, S
4, 64, 82
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5, 13, 22, 63, 67,
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69, 80
Gonzalez-Izquierdo, M
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Gowri, V
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Gulati, M
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Grants/
Research
Support
Speaker's
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1, 13, 26, 67,
2, 13, 67
87, 88
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13, 16, 26, 29, •
33, 44, 51, 60,
63, 67, 72, 84
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15
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12, 62, 84
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5, 63, 87
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Royalties/ Editorial
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69
Disclosures (continued)
Name
Board of Consultant/ Directors/
Advisory Stock/
Trustees Employment
Board
Shareholder
Grants/
Research
Support
Speaker's
Bureau
Harlow, S
•
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Harris, S
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5, 28, 37, 51, 73
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•
5, 28, 36, 37, 60, 73, 75, 87
Heisler, C
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Helmrich, G
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Jamadar, R
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Jenkins, M
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Jiang, X
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Joffe, H
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83
•
13, 34, 38, 55, •
56, 57
Jorgensen, M
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Kagan, R
•
• 5, 14, 25, 35, 51, 63, •
14, 15, 16, 5, 62, 63
66, 67, 80
25, 67
Kahler, K
•
60
•
60
•
•
Karim, R
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•
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Kaunitz, A
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13, 51, 84
•
2, 13, 29, 48, •
61, 84
Kearns, A
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Khan, S
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Kim, JH
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Kim, T
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Klein, W
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Krychman, M
27
•
67, 78
•
•
87
Ku, SY
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LaCroix, A
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Laughlin, G
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Lee, JY
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Lima, SM
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Lindsay, R
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5, 28
•
28
5, 28, 60, 87
Lombardi, A
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51
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Looby, S
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Maamari, R
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63
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Maki, P
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Marsh, W
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Meagher, E
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Megibow, A
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Mills, K
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Minkin, MJ
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13, 30, 62, 63, 67
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Monterrosa-Castro, A
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Moral, L
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Morrow, M
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70
Royalties/ Editorial
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Name
Board of Consultant/ Directors/
Advisory Stock/
Trustees Employment
Board
Shareholder
Mosca, L
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Murray, T
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Nachtigall, L
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Nahas, E
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Naser, B
•
76
Newton, K
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Nichols, A
*
67
Ogando, B
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Ojo, F
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Pace, D
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Padua, M
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Pal, L
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Palacios, S
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Parry, B
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Pearlstein, T
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Pettit, S
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Pinkerton, J
16, 40
85
Portman, D
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21
Prairie, B
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Randolph, J
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Reame, N
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Reed, S
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Reichman, W
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Rocha, J
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Rouen, P
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Sang, JH
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Sathyanarayana, R
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25
Schiff, I
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Schnatz, P
32, 53
•
Shah, S
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67
Shapiro, M
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Shifren, J
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Sievert, L
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Simon, J
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Siyam, T
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Snabes, M
•
15
Grants/
Research
Support
Speaker's
Bureau
74, 75
•
•
37
•
•
•
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63, 77
•
77
12, 62, 86
•
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•
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63
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63
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5, 8, 13, 79
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5, 7, 13, 67, 79
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•
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67
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5, 16, 25, 63, 67, 84
•
25, 29, 67
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13, 25, 29, 61, 67, •
13, 29, 67, 72, 84 67, 84
72, 80, 84
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13, 30, 62, 63, 67
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59
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16
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1, 2, 5, 9, 12, 16, •
15, 16, 29, 62, 5, 9, 13, 16, 25, 31, 49, 51, 52,
63, 84
45, 51, 60, 62,
58, 62, 63, 67, 80,
63, 84, 87
84, 87, 88
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20, 43, 50, 65
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71
Disclosures (continued)
Name
Board of Consultant/ Directors/
Advisory Stock/
Trustees Employment
Board
Shareholder
Soares, C
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Soares, J
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Speck, P
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Stojanovska, L
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Streicher, L
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Stuenkel, C
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Sulak, P
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Tagliaferri, M
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14
Teixeira de
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Araujo Moraes, S
Teixeira Gomes, R
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Terauchi, M
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Thurston, R
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Tilly, J
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Tough, K
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Uchiyama, S
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Ueno, T
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Utian, W
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Velasco, M
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Verna, C
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Warren, M
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Weber, M
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Wheeler, C
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Whiteley, J
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67
Zacarias-Flores, M
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Zummo, J
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83
72
11, 13, 28, 46, •
67, 89
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41
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14
14
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13, 14, 19, 42, 47, 51, 62, 68
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67, 72, 90
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Research
Support
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3, 11, 17, 28, 11, 13, 28, 39, 54, 67, 70 46, 67, 89
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Invited Speakers’ Recommended Reading
NOTE: References have been included as submitted by
speakers and have not been edited.
Raquel D. Arias, MD
Labrie F, Archer D, Bouchard C, et al. Intravaginal dehydroepiandrosterone
(Prasterone), a physiological and highly efficient treatment of vaginal atrophy.
Menopause 2009;16:907-922.
Shulman LP. Selective estrogen receptor modulators and vulvovaginal
atrophy: can we improve the lives of our patients with new therapeutic
options? Menopause 2010;17:452-453.
Chollet JA, Carter G, Meyn LA, Mermelstein F, Balk JL. Efficacy and safety of
vaginal estriol and progesterone in postmenopausal women with atrophic
vaginitis. Menopause 2009;16:978-983.
Murray A. Freedman, MS, MD
Freedman MA, Nolan TE. Genital Atrophy: An Inevitable Consequence of
Estrogen Deficiency. Female Patient 1996;21:62-66.
Freedman MA. Sexuality and the Menopausal Woman. Contem Obstet Gynecol
2000;45(suppl):4-18.
Freedman MA. Vaginal pH, Estrogen and Genital Atrophy. Menopause Manage
2008;17:9-13.
Sturdee DW, Panay N. On behalf of the International Menopause Society
Writing Group. Recommendations for the Management of Postmenopausal
Vaginal Atrophy. Climacteric 2010;13:509-522.
Pinkerton JV. Vaginal Impact of Menopause-related Estrogen Deficiency. OBG
Manage 2010;11(suppl):S2-7.
Lee YK, Chung HH, Kim JW, Park NH, Song YS, Kang SB. Vaginal pH-balanced
gel for the control of atrophic vaginitis among breast cancer survivors: a
randomized controlled trial. Obstet Gynecol 2011;117:922-927.
Goldstein I. Recognizing and Treating Urogenital Atrophy in Postmenopausal
women. J Women’s Health 2010;19(3):425-432.
Herbert Benson, MD
Goldstein SR. The endometrial echo revisited: have we created a monster? Am
J Obstet Gynecol. 2004;191:1092-6.
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Benson H, Proctor W. Relaxation Revolution. New York: Scribner, 2010.
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Dusek J, Yeung A. Exploring the effectiveness of a comprehensive mind body
intervention for medical symptom relief. J Altern Complement Med, 2010:
16(2):1-6.
Susan R. Davis, MBBS, FRACP, PhD
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in adult females: changes with age, menopause, and oophorectomy. J Clin
Endocrinol Metab, 90:3847-3853
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Stuckey BGA, Wlodarczyk J, Gard’ner K, Humberstone A. 2008, Safety and
Efficacy of a Testosterone Metered-Dose Transdermal Spray for treatment
of decreased sexual satisfaction in Premenopausal Women: A
Placebo-Controlled Randomized, Dose-Ranging Study. Annals Internal Med,
148:569-577.
Davis SR, Goldstat R, Papalia MA, Shah SM, Kulkarni J, Donath S, Bell R.
2006, Effects of aromatase inhibition on sexual function and wellbeing in
postmenopausal women treated with testosterone: a randomized placebo
controlled trial. Menopause, New York, NY 13:37-45.
Davis SR, Moreau M, Kroll R, Bouchard C, Panay N, Gass M, Braunstein GD,
Linden-Hirschberg A, Rodenberg C, Pack S, Koch H, Moufarage A, Studd J.
2008, Testosterone for Low Libido in Menopausal Women Not Taking Estrogen
Therapy. N Eng J Med, 359:2005-2017
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Colditz GA, Hankinson SE. 2010, The association of plasma androgen levels
with breast, ovarian and endometrial cancer risk factors among
postmenopausal women. International Journal of Cancer, 126:199-207
Steven R. Goldstein, MD, FACOG, CCD, NCMP
Levine D, Brown DL, Andreotti RF, Benacerraf B, Benson CB, Brewster WR,
Coleman B, DePriest P, Doubilet PM, Goldstein SR, Hamper UM, Hecht JL,
Horrow M, Hur HC, Marnach M, Patel MD, Platt LD, Puscheck E, SmithBindman R. Management of asymptomatic ovarian and other adnexal cysts
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Ferrazzi E, Zupi E, Leone FP, Savelli L, Omodei U, Moscarini M, Barbieri M,
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Sideri M, Solima E, Spazzini D, Testa AC, Vignali M. How often are endometrial
polyps malignant in asymptomatic postmenopausal women? A multicenter
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Martha Gulati, MD, MS, FACC, FAHA
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outcomes in women with nonobstructive coronary artery disease: a report
from the Women’s Ischemia Syndrome Evaluation Study and the St James
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Bugiardini R, Bairey Merz CN. Angina with “normal” coronary arteries: a
changing philosophy. JAMA 2005;293:477-84.
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prevention of cardiovascular disease in women--2011 update: a guideline
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73
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Steven T. Harris, MD, FACP
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symptoms in breast cancer patients. Maturitas 2011;68:148-154.
Ross AC, Manson JE, Abrams SA, et al. The 2011 report on Dietary Reference
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Candace J. Heisler, JD
Patricia M. Speck, DNSc, APN, FNP-BC, DF-IAFN, FAAFS, FAAN
Bonnie RJ, Wallace RB (Eds.) 2003. Panel to Review Risk and Prevalence of
Elder Abuse and Neglect. Committee on National Statistics and Committee
on Law and Justice, Division of Behavioral and Social Sciences and Education
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in an aging America. Washington, DC: National Academies Press.
Brandl B, Dyer CB, Heisler CJ, Otto JM, Stiegel LA, Thomas RW. 2007. Elder
abuse detection and intervention: A collabora¬tive approach. New York:
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inhibitor-induced bone loss using risedronate: the SABRE trial. J Clin Oncol
2010;28:967-975.
Din OS, Dodwell D, Wakefield RJ, Coleman RE. Aromatase inhibitor-induced
arthralgia in early breast cancer: what do we know and how can we find out
more? Breast Cancer Res Treat 2010;120:525-538.
Gail A. Laughlin, PhD
Laughlin GA, Barrett-Connor E, Kritz-Silverstein D, von Muhlen D.
Hysterectomy, oophorectomy, and endogenous sex hormone levels in older
women: The Rancho Bernardo Study. J Clin Endocrinol Metab 2000;85:645-651.
Dong X. 2005. Medical implications of elder abuse and neglect, Gorbien MJ,
Ed. Clinics in geriatric medicine, 21(2), 293–313.
Laughlin GA, Barrett-Connor E. Sexual dimorphism in the influence of
advanced aging on adrenal hormone levels: The Rancho Bernardo Study. J
Clin Endocrinol Metab 2000;85:3561-3568.
Dyer CB, Connolly MT, McFeeley P. 2003. The clinical and medical forensics of
elder abuse and neglect. In Bonnie RJ & Wallace RB (Eds.) Elder mistreatment:
Abuse neglect and exploitation in an aging America, pp. 339.
Laughlin GA, Barrett-Connor E, May S. Sex-specific association of the
androgen to estrogen ratio with adipocytokine levels in older adults: The
Rancho Bernardo Study. Clin Endocrinol (Oxf ). 65(4):506-13, 2006.
Mosqueda L, Burnight K, Liao S. 2005. The life cycle of bruises in older
adults/ Journal of the American Geriatrics Society, 53, 1339–1343.
Laughlin GA, Barrett-Connor E, Bergstrom J. Low serum testosterone and
mortality in older men. J Clin Endocrinol Metab, 2008;93:68-75.
Ramsey-Klawsnik H, Teaster P, Mendiondo M, Marcum J, Abner E. 2008. Sexual
predators who target elders: Findings from the first national study of sexual
abuse in care facilities. Journal of Elder Abuse & Neglect, 20(4), 353–376.
Laughlin GA, Goodell V, Barrett-Connor E. Extremes of endogenous
testosterone are associated with increased risk of incident coronary events
in older women. J Clin Endocrinol Metab 2010;95:740-747.
Hadine Joffe, MD, MSc
Emma A. Meagher, MD
Joffe H, Petrillo L, Koukopoulos A, Viguera AC, Hirschberg A, Nonacs R, Somley
B, Pasciullo E, White DP, Hall JE, Cohen LS. Increased estradiol and improved
sleep, but not hot flashes, predict enhanced mood during the menopausal
transition. J Clin Endo Metab 2011 Jul;96(7):E1044-54.
Mosca L, Benjamin EJ, Berra K, et al. Effectiveness-based guidelines for the
prevention of cardiovascular disease in women—2011 Update: a guideline
from the American Heart Association. Circulation 2011;123:1243-1262.
Joffe H, Partridge A, Giobbie-Hurder A, Li X, Habin K, Goss P, Winer E, Garber
J. Augmentation of venlafaxine and SSRI’s with zolpidem improves sleep
and quality-of-life in breast cancer patients with hot flashes: a randomized
double-blind placebo-controlled trial. Menopause 2010;17(5):908-16.
Joffe H, Petrillo L, Viguera A, Koukopoulos A, Silver-Heilman K, Farrell A, Yu G,
Silver M, Cohen LS. Eszopiclone improves insomnia, depressive and anxious
symptoms in perimenopausal and postmenopausal women with hot flashes: a randomized, double-blinded, placebo-controlled cross-over trial. Am J
Obstet Gynecol 2010;202(2):171.e1.e11.
Joffe H, Soares CN, Thurston RC, White DP, Cohen LS, Hall JE. Depression
is associated with worse objectively and subjectively measured sleep,
but not more frequent awakenings, in women with VMS. Menopause
2009;16(4):671-9.
Payne JL, Teitelbaum-Palmer J, Joffe H. A reproductive subtype of depression:
conceptualizing models and moving towards etiology. Harv Rev Psychiatry
2009; 17(2):72-86.
74
Baigent C, Keech A, Kearney PM, et al, for the Cholesterol Treatment Trialists’
(CTT) Collaborators. Efficacy and safety of cholesterol-lowering treatment:
prospective meta-analysis of data from 90,056 participants in 14 randomised
trials of statins. Lancet 2005;366:1267-1278.
Kearney PM, Blackwell L, Collins R, Keech A, Simes J, Baigent C, for the
Cholesterol Treatment Trialists’ (CTT) Collaborators. Efficacy of
cholesterol-lowering therapy in 18,686 people with diabetes in 14
randomised trials of statins: a meta-analysis. Lancet, 2008;371:117-125.
Ridker PM, Danielson E, Fonseca FA, et al. Rosuvastatin to prevent vascular
events in men and women with elevated C-reactive protein. N Engl J Med
2008;359:2195-2207.
Miller M, Stone NJ, Ballantyne C, et al. Triglycerides and cardiovascular
disease: a scientific statement from the American Heart Association.
Circulation 2011;123:2292-2333.
Alec J. Megibow, MD, MPH, FACH
Lori J. Mosca, MD, MPH, PhD
Berland LL, Silverman SG, Gore RM, et al. Managing incidental findings on
abdominal CT: white paper of the ACR incidental findings committee. J Am
Coll Radiol 2010;7:754-773.
American Heart Association. Heart Disease and Stroke Statistics – 2011
Update. Dallas, Texas: American Heart Association; 2011.
Berland LL. The American College of Radiology strategy for managing
incidental findings on abdominal computed tomography. Radiol Clin North
Am 2010;49:237-243.
Berlin L. The incidentaloma: a medicolegal dilemma. Radiol Clin North Am
2011;49:245-255.
Megibow AJ. Preface imaging of incidentalomas. Radiol Clin North Am
2011;49:xi-xii.
Mary Jane Minkin, MD, FACOG, NCMP
Loprinzi CI, Wolf SL, Barton DI, Laack NN. Symptom management in
premenopausal patients with breast cancer. Lancet 2008; 9:993-1001.
Mosca L, et al. Twelve-Year Follow up of American Women’s Awareness of
Cardiovascular Disease (CVD) Risk and Barriers to Heart Health. Circ Cardiovasc
Qual Outcomes 2010;3:120127.
Mosca L, et al. Effectiveness-Based Guidelines for the Prevention of
Cardiovascular Disease in Women -- 2011 Update: A Guideline From the
American Heart Association. Circulation, 2011;123(11):1243-62
Thomas H. Murray, PhD
NIH-DOE Working Group on Ethical, Legal and Social Implications of Human
Genome Research. Genetic Information and Health Insurance Report of the Task
Force on Genetic Information and Insurance. Bethesda, MD: Department of
Health and Human Services, 1993.
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2005;118 Suppl 12B:98-108.
Murray TH. Genetic exceptionalism and “future diaries”: Is genetic information
different from other medical information? In Rothstein M, ed. Genetic Secrets.
New Haven: Yale University Press, 1997:71.
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hot flashes: systematic review and meta-analysis. JAMA 2006;295:2057-2071.
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policy, and practical considerations. J Law Med Ethics 1995;23:360-366.
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treatment of breast cancer: 14. The role of hormone replacement therapy in
women with a previous diagnosis of breast cancer. CMAJ 2002;166:1017-1022.
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Rep 1992;22:12-17.
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racemosa): safety and efficacy for cancer patients. Support Care Cancer
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Green MJ, Botkin JR. Genetic exceptionalism in medicine: Clarifying the
differences between genetic and nongenetic tests. Ann Intern Med
2003;138:571-575.
Monica Morrow, MD, FACS
Suter S. The allure and peril of genetics exceptionalism: Do we need special
genetics legislation. Wash Univ Law Q 2001;79:669-748.
Morrow M. Magnetic resonance imaging for screening, diagnosis,
eligibility for breast conserving surgery: promises and pitfalls. Surg Oncol Clinics
NA 2010;19:475-492.
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resonance imaging in breast cancer staging: systemic review and meta-analysis
in detection of multifocal and multi-centric cancer. J Clin Oncol
2008;26:3248-3258.
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cancer (COMICE) trial: a randomized controlled trial. Lancet 2010;375:563-571.
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resonance imaging to screen women at high risk for breast cancer. Ann Int Med
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during the menopausal transition and beyond. Psychiatr Clin North Am
2010;33:295-308.
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management of major depressive disorder in perimenopausal and
postmenopausal women. Prim Care Companion J Clin Psychiatry
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sleep, but not hot flashes, predict enhanced mood during the menopausal
transition. J Clin Endocrinol Metab 2011;96:E1044-1054.
75
Invited Speakers’ Recommended Reading (continued)
William E. Reichman, MD
Reichman WE, Fiocco AJ, Rose NS. Exercising the brain to avoid cognitive
decline: examining the evidence. Aging Health 2010;6:565-584.
Jack CR, Jr, Albert MS, Knopman DS, et al. Introduction to the
recommendations from the National Institute on Aging and the Alzheimer’s
Association workgroup on diagnostic guidelines for Alzheimer’s disease.
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Valenzuela M, Sachdev P. Can cognitivie exercise prevent the onset of
dementia? Systematic review of randomized clinical trials with longitudinal
follow-up. Am J Geriatr Psychiatry 2009;17:179-187.
Sitzer DI, Twamley EW, Jest DV. Cognitive training in Alzheimer’s disease: a
meta-analysis of the literature. Acta Psychiatr Scand 2006;114:75-90.
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in the elderly. N Engl J Med 2003;348:2508-2516.Not submitted in time for
Patricia J. Sulak, MD
AHA/ACCF 2009 performance measures for primary prevention of
cardiovascular disease in adults: a report of the American College of
Cardiology Foundation/American Heart Association task force on
performance measures (writing committee to develop performance
measures for primary prevention of cardiovascular disease): developed in
collaboration with the American Academy of Family Physicians; American
Association of Cardiovascular and Pulmonary Rehabilitation; and Preventive
Cardiovascular Nurses Association: endorsed by the American College of
Preventive Medicine, American College of Sports Medicine, and Society for
Women’s Health Research. Circulation 2009;120:1296-1336.
Sofi F, Cesari F, Abbate R, Gensini GF, Casini A. Adherence to a Mediterranean
diet and health status: meta-analysis. BMJ 2008;337:1344-1336.
Villareal DT, Chode S, Parimi N, et al. Weight loss, exercise, or both and
physical function in obese older adults. N Engl J Med 2011;364:1218-1229.
Jonathan L. Tilly, PhD
Perez GI, Robles R, Knudson CM, Flaws JA, Korsmeyer SJ, Tilly JL. Prolongation
of ovarian lifespan into advanced chronological age by Bax deficiency. Nat
Genet 1999;21:200-203.
Tilly JL. Commuting the death sentence: how oocytes strive to survive. Nat
Rev Mol Cell Bio 2001;2:838-848.
Johnson J, Canning J, Kaneko T, Pru JK, Tilly JL. Germline stem cells and
follicular renewal in the postnatal mammalian ovary. Nature 2004;428:145-150.
Perez GI, Jurisicova A, Wise L, Lipina T, Kanisek M, Bechard A, Takai Y, Hunt P,
Roder J, Grynpas M, Tilly JL. Absence of the pro-apoptotic Bax protein extends
fertility and alleviates age-related health complications in female mice.
Proceedings of the National Academy of Sciences USA 2007;104:5229-5234.
Selesniemi K, Lee H-J, Muhlhauser A, Tilly JL. Prevention of maternal
aging-associated oocyte aneuploidy and meiotic spindle defects in mice by
dietary and genetic strategies. Proceedings of the National Academy of Sciences
USA 2011;(in press).
76
Demonstrate your interest & expertise…
Become a NAMS Certified Menopause
Practitioner (NCMP)
As the definitive menopause resource, The North American Menopause
Society (NAMS) developed this competency examination for healthcare
providers who want to demonstrate their expertise in the field of
menopause management. Passing the exam leads to the prestigious NAMS
Certified Menopause Practitioner credential. Benefits include:
•Validation by the preeminent menopause organization that you are a
menopause expert
•Possibility of more patient referrals, job promotion, and higher salaries
•Enhanced credibility with your peers and the personal satisfaction of
providing your patients with the best possible care
•A certificate suitable for framing
•Annual lapel pins, which help promote your achievement to patients
and colleagues
•Pride of using “NCMP” alongside your other credentials
Move your career forward and validate your level of
knowledge to your patients and peers!
“With
new menopauserelated information
emerging and confusion about
hormone therapy, our patients and
colleagues are looking for providers
who can guide them with the latest,
up-to-date recommendations. The
NCMP credential is a great way to let
them know about your expertise.”
– Peter F. Schnatz, DO,
FACOG, NCMP,
Reading, PA
“By
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exam and maintaining my
credential, I have proved that
I am continuing to keep up with
the latest menopause information.
I am the go-to physician in my
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one of the first
Canadian nurses to
– Robyn B. Faye, MD, NCMP,
hold the NAMS Menopause
Ft. Washington, PA
Practitioner credential, I feel
I am empowered and have
increased autonomy, accountability,
and job satisfaction.”
– Sally J. Payette, RN,
CME, NCMP,
Ottawa, ON,
Canada
To learn more about how to earn this prestigious
certification, or to apply for an upcoming
exam date, visit the NAMS website:
www.menopause.org/compexam.aspx
268
Menopause Practice:
A Clinician’s Guide
New Print & Digital Format
The North American Menopause Society is proud
to offer the fully updated and referenced fourth
edition of its leading professional resource.
Edited by dozens of experts in the field, this
comprehensive clinical practice textbook is
available in both print and digital formats.
Featuring:
•Digitalformatupdatedasimportant
new information is available
•CMEcreditavailablethrough2013
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For members:
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To order, go to www.menopause.org
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“This current, annotated resource is for all clinicians
caring for menopausal women. It is also an invaluable
tool for teaching medical students and staff.”
Risa Kagan, MD, FACOG, CCD, NCMP
Berkeley, CA
265
Submit your abstracts to NAMS for presentation at the
23rd Annual Meeting
Gaylord Palms Hotel
Orlando, Florida
October 3–6, 2012
Submit your abstract through the
NAMS website: www.menopause.org
• T heabstractsubmissionsite
willopeninJanuary2012
• AbstractsubmissiondeadlineisApril30,2012
• T opabstractswillbeacceptedfororal
presentationanduptofourposterprizes
willbeawarded(topprize:$1,000)
• A
cceptedabstractswillbepublished
intheNAMSjournal,Menopause
269
©2011 The North American Menopause Society
Printed in USA – September 2011 – AM11ABST