Puzzles of Perimenopause - the British Columbia Society of

Transcription

Puzzles of Perimenopause
Jerilynn C. Prior
University of British Columbia
Centre for Menstrual Cycle and Ovulation Research
www.cemcor.ubc.ca
JcPrior 2010
At the end of this talk you will know:
Accurate names for women’s aging that
mirror physiology, not politics
High, erratic estrogen levels in
perimenopause are ignored / denied
Perimenopause starts while flow is regular
No randomized, placebo-controlled trial
data prove effective therapy
JcPrior 2010
What’s the Context for Perimenopause?
Demographics
of the “baby-boom” generation
19% of Canadian women now 40-55 Stats Canada
“HRT” discredited by strong science Beral Lancet 2002
Oprah/Suzanne–natural hormones deemed good
Estrogen treated positively—news, magazines
Women question physicians’ wisdom & motives
36 million in USA just “got” health insurance
JcPrior 2010
43 year old married woman with 2 children
Heavy, frequent flow, increased cramps
Sore, swollen breasts most of cycle
Night sweats waking her every night
Trouble coping. . . .
She asks – what’s the matter with me?
JcPrior 2010
You will know at the end of this talk:
JcPrior 2010
Climacteric
Change of Life
Menopause
Decline of Life
Menopausal Transition
Postmenopause
Perimenopause
JcPrior 2010
Context—Language
Menopause definition
“Menopause is the transition period in a
woman's life when her ovaries stop producing
eggs, her body produces less estrogen and
progesterone, and menstruation becomes
less frequent, eventually stopping altogether.”
NY Times Health section—April 18, 2010
JcPrior 2010
Context—Language
“Menopause” has three different meanings!
Everything (miserable) that’s changing in
midlife or older women
Final menstrual period (literally)
Women’s normal life phase beginning one
year following the final menstrual period
JcPrior 2010
Final Menstrual Period
(FMP)
(Menopause)
Menopause transition
Postmenopause
Perimenopause
12 months
WHO Research “Menopause in the 1990s” #96238
JcPrior 2010
Context = Language
Postmenopause means: a woman after her
“final” flow who is now, by definition, diseased
estrogen deficiency
heart disease
osteoporosis
dementia
(lack of social and sexual appeal & relevance)
JcPrior 2010
Life Cycle of Estrogen
Estrogen
Levels
childhood teens premenopause perimenopause
menopause
JcPrior 2010
Hormonal Life Cycles
of Women and Men
Testosterone
Levels
Estrogen
Levels
birth
teens
adulthood
older adulthood
older ages
JcPrior 2010
Is Olivia estrogen deficient?
JcPrior 2010
JcPrior 2010
JcPrior 2010
How do Hormones Change in
Perimenopause?
We believe that
estrogen
starts
to
drop
and
get low
JcPrior 2010
JcPrior 2010
Premenopausal levels = gold standard
Flow
Flow
%
1400%
Change
Progesterone
from
flow
Estrogen
220%
1
4
8
12
16
20
24
28
M enst r ual C ycl e D ay
adapted from Nielsen J. Clin Endocr. Metab 1990;70:1431
JcPrior 2010
Endocrine Changes
Melbourne Midlife Women’s Health Study
Random population-based sample
Women ages 45-55
No hormonal therapy, or Pill
Flow within the last three months—no hysterectomy
438 women were eligible and joined;
Participation rate = 56%
Mean age 49, BMI 25.9—a healthy cohort
Burger, H, JCEM, 1995:80:3537
JcPrior 2010
Endocrine Changes
Classification of women:
I no change in flow or cycle length
II change in flow
III change in cycle length
IV change flow & cycle length
V no flow for more than 3 and less than 12 mo
Estrogen levels: days 3-8 of menstrual cycle, in a.m.
once each year. Analyzed by geometric mean
Burger, H, JCEM, 1995:80:3537
JcPrior 2010
Burger, H., JCEM, 1995:80:3537
JcPrior 2010
Mid-cycle
Peak
Day 3-8
Modified from Burger, H., JCEM, 1995:80:3537
Endocrine Changes
“We conclude that an increase in serum FSH
and decreases in E2 and Inhibin are the
major endocrine changes. . .menopausal
transition.”
Burger, H., JCEM, 1995:80:3537
Estrogen levels are “relatively preserved” in
the menopausal transition
Henry Burger 2007
JcPrior 2010
Endocrine Changes
500
**
400
Estradiol
levels
pmol/L
± SD
300
*
Premenopausal
Perimenopausal
200
100
0
N = 292 N = 415
Follicular Phase
N = 250 N = 69
Premenstrual Phase
(days 3-8)
* Fisher’s F = 16.12, P=0.041; **Fisher’s F = 15.46, P=0.016
JcPrior Endocrine Reviews 1998; 19: 397-428
JcPrior 2010
Estrogen is 26%↑
↑
500
**
400
Estradiol
levels
pmol/L
± SD
300
Premenopausal
Perimenopausal
*
200
100
0
N = 292 N = 415
Follicular Phase
N = 250 N = 69
Premenstrual Phase
(days 3-8)
* Fisher’s F = 16.12, P=0.041; **Fisher’s F = 15.46, P=0.016
JcPrior Endocrine Reviews 1998; 19: 397-428
JcPrior 2010
Endocrine Changes
New data—from a prospective, observational,
controlled study from Australia
“Progression through the STRAW [midlife] stages. .
. is associated with elevations in FSH, LH and
estradiol and decreases in luteal phase
progesterone.” Hale G E J Clin Endoc Metab 2007;92:3060
Unreliable hypothalamic-pituitary-ovarian feedback
connections (aging of both the brain and the ovary)
means that taking estrogen doesn’t suppress our own levels
JcPrior 2010
Endocrine Changes
Estrogen
Progesterone
JcPrior 2010
Life Cycle of Progesterone
Progesterone
Levels
childhood teens
premenopause
perimenopause
menopause
JcPrior 2010
↑Estrogen and ↓Progesterone in Perimenopause
LOOP→
→
Shideler Maturitas 1989
JcPrior 2010
Sore breasts, swollen breasts most of cycle
Night sweats
Trouble coping “When do I get my life back?”
FSH on cycle day 3 is 4, which is normal for
premenopause
Hemoglobin and ferritin low (anemia, loss of blood
and not enough iron)
JcPrior 2010
Climacteric
Change of Life
Menopause
Decline of Life
Postmenopause
Perimenopause
JcPrior 2010
JcPrior 2010
Staging of Reproductive Aging
Workshop (STRAW)
Soules et al. Fertil Steril 2001;76(5):874
JcPrior 2010
JcPrior 2010
Daily Perimenopause Diary
Puzzle of Perimenopause--video
JcPrior 2010
Heavy
flow
Hot flushes
Night sweats
Sleep
problems
JcPrior 2010
Regularly Menstruating Women
Ages 36-48
N = 98 cycles, 24 women
Analysis by 3-way ANOVA
Menstrual Flow
Flow
*
2.5
2
1.5
1
0.5
0
MN
Front Breast Tenderness *
MC
PM
MC
PM
1.5
Breast tenderness—
front
*
1
0.5
0
MN
Nighttime Vasomotor Symptoms *
Night
sweats
*
1.5
1
0.5
0
Hot Flushes during
sleep and cyclic, around
the menstrual period
MN
MC
PM
Hale G Climacteric 2003;6:128
JcPrior 2010
Perimenopause Diagnosis
Women with regular cycles—any 3 of these:
New onset heavy and/or longer flow
Shorter menstrual cycles (≤ 25 days)
New sore, swollen or lumpy breasts
New mid-sleep wakening
Increased cramps
Onset of night sweats, in particular premenstrually
New or markedly increased migraine headaches
New / increased premenstrual mood swings
Weight gain without changes in exercise or eating
Prior JC BC Medical Assn. J 2005
JcPrior 2010
Sore breasts, swollen breasts most of cycle
Night sweats
Trouble coping “When do I get my life back?”
She’s in perimenopause
JcPrior 2010
Climacteric
Change of Life
Menopause
Decline of Life
Postmenopause
Perimenopause
JcPrior 2010
Phases of Perimenopause
Changes in
Experience
Phase
A
Irregular
periods
B
Final
period
C
D
Menopause
E
Time
2-5 years
± 3 years
1 year
Prior JC. “Ovulatory Changes with Perimenopause” Endocrine Facets of
Ageing 2003, John Wiley & Sons, Ltd. Rexdale, Ontario, Canada
JcPrior 2010
Language Summary
“Menopause” = Perimenopause
Postmenopause = Menopause
Menopause Transition = (Later Perimenopause)
JcPrior 2010
JcPrior 2010
20/80
JcPrior 2010
Doctors Reported Difficulty Treating. . .
80
70
60
50
40
Percentage of HCP
30
20
10
er
ris
k
an
c
Pa
in
C
s
St
re
s
Sl
ee
p
H
or
m
on
es
M
en
st
ru
al
Se
xu
B
al
on
e
he
H
al
ig
th
h
es
tro
ge
n
S
VM
oo
d
0
M
Percentage of HCP
Health Care Provider Concerns
Category
JcPrior 2010
CeMCOR Perimenopausal Interference Questionnaire
During the past 3 months have any of the body changes of perimenopause
interfered with your usual activities?
0
1
2
No interference
3
4
5
6
7
8
9
10
Extreme Interference
During the past 3 months have any of the mood changes of perimenopause
interfered with your usual activities?
0
1
2
No interference
3
4
5
6
7
8
9
10
Extreme Interference
JcPrior 2010
What will help this perimenopausal woman?
Exercise regularly!
Eat right!
Reduce stress!
Perimenopause is a phase—You’ll get over it!
Absolutely necessary!
But not
sufficient for the symptomatic 20%!
JcPrior 2010
Treatments
Estrogen “replacement”
Black cohosh
Low-dose Oral Contraceptives
Hormone “replacement” therapy (“HRT”)
“I don’t want anything—it’s natural!”
Bio-identical hormones—estradiol, testosterone and
progesterone
Mirena IUD
Cyclic Progesterone
Depo-Provera
GnRH agonists
Evening Primrose Oil
JcPrior 2010
Therapies
Evidence-based therapies—effective and
safe from randomized controlled trials
NONE!
JcPrior 2010
“Estrogen therapy for Menopause. . .”
Canadian Multicentre Osteoporosis Study—a
population-based, randomly sampled cohort of 9423
women and men followed for 12 years so far.
Perimenopausal women (ages 43-63):
Women with cycles in last year, or
Women with hysterectomy, ovaries intact, age < 55
33% are current users of estrogen therapy
unpublished data Prior 11/05
JcPrior 2010
Susan Baxter PhD,
Jerilynn C. Prior MD
Praeger Press, Conn.
USA, 2009
JcPrior 2010
Treatment: very heavy flow
Ibuprofen on heavy flow days—↓ flow by 25-40%
Progesterone—high dose, long cycle days 6-27—
will ↓ flow by 75%. Also:
Helps with hot flushes
Helps breast tenderness/lumps
Progesterone significantly increases deep sleep
Tranexamic acid—wt-adjusted TID X 3 days—↓
flow by 35-50% (an emergency measure)
Levonorgestrol-releasing IUD (Mirena®)—↓ flow
by 80-90%
JcPrior 2010
Life Cycle of Progesterone
Progesterone
Levels
childhood teens
premenopause
perimenopause
menopause
JcPrior 2010
Cyclic Progesterone Therapy
flow
flow
Oral Micronized
Progesterone (300 mg at
Bedtime on days 14-27
1
14
27
Cycle days
Cyclic Progesterone Therapy-www.cemcor.ubc.ca
JcPrior 2010
Prize Winner
Finalist in Health—Independent
Book Publishers of North America-2006
Fiction
First person woman doctor
8 highly symptomatic perimenopausal
women
Different attitudes, backgrounds
walks of life, families, cultures
Its purpose is education—glossary,
over 100 scientific citations, many
figures and drawings.
Order through your favourite bookstore
All profit supports the Centre for
Menstrual Cycle & Ovulation Research
JcPrior 2010
“Menopause”
Hormone
Changes
Symptoms
from:
Therapy
Perimenopause
E2 ↑26%
Progesterone ↓
(P4), ↑ cortisol
↓ E2 , ± empty
↑↑ E2, ↓ P4,
nest, depression ↑ cortisol
The Pill
Information,
“ERT” or “HRT” Cyclic / daily P4
Dropping (E2)
estrogen levels
JcPrior 2010
Summary:
“Perimenopause” is the appropriate name
for our midlife transition
High, erratic estrogen levels, and lower
progesterone levels cause symptoms for
20% in perimenopause
Perimenopause begins in women with
regular flow
Progesterone counterbalances high
estrogen and helps sleep—CeMCOR just got
funding for RCT of progesterone for Perimenopausal
Night Sweats
JcPrior 2010
Phases of Perimenopause
Changes in
Experience
Phase
A
Irregular
periods
B
Final
period
C
D
Menopause
GRADUATION !
E
Time
2-5 years
± 3 years
1 year
Prior JC. “Ovulatory Changes with Perimenopause” Endocrine Facets of
Ageing 2003, John Wiley & Sons, Ltd. Rexdale, Ontario, Canada
JcPrior 2010
Centre for
Menstrual
Cycle &
Ovulation
Research
www.CeMCOR.ubc.ca
JcPrior 2010

Puzzles of Perimenopause - the British Columbia Society of

Transcription

Similar documents