Susan E.D. Doughty, APRN, CWHNP

WE ARE NOT MERELY TRAVELERS
WE ARE THE NAVIGATORS of OUR DESTINY
Susan E.D. Doughty, APRN, CWHNP
Coastal Women’s HealthCare
Scarborough, ME
OBJECTIVES
Describe the physiologic processes that
contribute to symptoms of peri/post
menopause
Summarize what was learned from WHI
regarding EPT/MHT/HT
List evidence-based strategies for
symptom management, including
complementary therapies
OBJECTIVES
Identify components of a benefit-risk tool
to evaluate HT use
Combine information gathered to
individualize therapy to optimize health
and QOL for your midlife patient
PATIENT # 1
E.W. 54yo, 3years since FMP
○ Persistent hot flashes during the day
○ Occasional night sweats, goes back to sleep
○ Type 2 diabetes
○ Borderline hypertension
○ Family history of osteoporosis
○ Dyspareunia
Best friend just started HT and wants you to
order it for her as well
PATIENT # 2
51yo skipping cycles, LMP 3 months ago
Hot flashes come, then go
Feeling sleep-deprived
History of postpartum depression, feeling “down”
BMI 18, skipped cycles with anorexia as teen
MGM with breast cancer at age 68,normal
mammograms
Wants symptom relief
Perimenopausal Symptoms
Heavy flow/anemia
Mid cycle bleeding
Spotting around
period
Increased emotional
lability
Shorter time
between periods
Longer time between
periods
Skipped periods
Hot flashes
Night sweats/insomnia
Joint pain
Postmenopausal Symptoms
Osteoporosis/
fracture
Dry, painful vagina
Increased frequency
of UTI
Decreased
libido/sexual
dysfunction
Urinary incontinence
Diminished noun/object
memory*
Skin dryness/loss of
elasticity*
Eye changes*
Hair changes*
*Not in this presentation
Menstrual Cycle
http://en.wikipedia.org/wiki/Image:MenstrualCycle2.png
Adrenal Gland
(Steroid Pathways)
Cholesterol
Pregnenolone
Progesterone
Hydroxypregnenolone
Hydroxyprogesterone
Cortisol
Dehydroepiandrosterone
(DHEA)
DHEA
Androstenedione
Estrone
Estriol
Testosterone
Estradiol
1993 NIH
Women’s Health Initiative-(WHI)
$628 million, 15 years
40 clinical centers
3 inter-related clinical trials-RCT, blinded
One observational study
Healthy postmenopausal women aged 50 to
79 (mean 63.2)
At entry, 7.7% with CVD
Wyeth provided all study drugs and
placebos
WHI
N=16,608
8506 CCEPT (with uterus)
○ 33.4% 50 to 59
○ 45.3% 60 to 69
○ 21.3% 70 to 79
○ Adherence
58% CCEPT
62% Placebo
10,739 ET only (without uterus)
Majority post-menopause 10 years
Informed consent:
“placebo may not prevent coronary artery
disease”
May 31, 2002
WHI-After mean of 5.2 years follow-up,
investigators on data and safety
monitoring board recommended
stopping trial arm of Prempro v. placebo
Test statistic for invasive breast cancer
exceeded the stopping boundary for this
adverse effect
Information was kept confidential until July.
JAMA (288) 321.
WHI Conclusions:
Among 10,000 Women
On Prempro
On placebo
BrCA
38*
30
CAD
37
30
CVA
28
21
DVT
34**
16
HipFx
10
15
Colon CA
10
16
Estrogen Only Arm WHI
Prematurely terminated at 6.8 years
Reason given: studies showed no
overall benefit, not because of
negative outcomes
JAMA (2004) 291: 1701-1712
WHI Conclusions: Estrogen Only Arm
Among 10,000 Women per year
On Premarin
On placebo
Strokes
44
32
DVT
21
15
Hip fractures
11
17
Colorectal
cancer*
Heart attacks*
17
16
49
54
Breast cancer*
26
33
*No statistical difference in risk
One Year Following WHI
2.7 million women on HT
(6 million women before WHI)
Recommendations:
1.
2.
3.
Individualize therapy
Do not use HT with CAD risk factors
Wean HT earlier-3 to 4 years
(no studies about best way to wean)
Use bisphosphonates, SERMS, Statins more
frequently
5. Use more half dose EPT, alternative routes
4.
25% to 50% resume EPT at lower dose
NAMS Panel: Recommendation for
Clinical Practice (2003)
1.
2.
3.
4.
Treatment of vasomotor symptoms
remains primary indication for HT
Use progestogens only in women with a
uterus
WHI/HERS data cannot be extrapolated
to women experiencing premature or
early menopause
Risk v. benefit must be considered when
using HT to treat postmenopausal
osteoporosis.
NAMS Panel: Recommendation for Clinical
Practice (2003)
5.
6.
7.
8.
Use of HT should be limited to the shortest
duration consistent with treatment goals,
benefits and risks for each individual vis a vis
quality of life
The lowest dose of HT needed to correct
symptoms should be used
Alternative routes of HT may offer advantages
but long term risk benefit ratios have not been
demonstrated
Individual risk profile is essential.
Quality of Life
Largely ignored in decade after publication
of WHI data
Lives saved by avoiding HT would justify
distress:
126,000 fewer breast cancers
76,000 fewer VTE and CV disease cases
145,000 QOL years with decreased
incidents
Climacteric (2012) 15:213-216.
Not taken into account:
263,000 more fractures
15,000 more colorectal cancers
Increased morbidity/mortality from CVD in
young patients denied HT
Fear of use of vaginal estrogen
Ann.Int.Med.(2014) 160: 549-602.
OBG.Mgt. (2014)n26: 1415.
Timing of HT (2013)
Growing body of data: safety and
efficacy of HT
Initiating within 10 years of FMP, under age
60
Continuing after age 60 for QOL
Providers still reluctant to prescribe
Push for 5 year limit
Discontinue after age 60
Obstet.Gynecol. (2013) : 172-176.
Conflicting Reports
Original reports overstated risks of HT
Recent Lancet article: increased incidence
(40%) of ovarian cancer on HT even less than 5
years
Growing body of evidence for continuing HT
after age 60 if needed for symptom
management, and risk of arterial event and
breast cancer low
Climacteric (2012) 15: 275-280.
Menopause (2007) 14: 1056-1059.
Evidence Re: Progestogens and BrCA
Limited data demonstrating safety of
progestogens on the breast
“Appears to contribute substantially to the
increased breast cancer risk seen with EPT
use.”
Continuous vs. Sequential unclear:
observational trials: risk greater with
continuous
Risk reverts to normal after 3 years off HT.
J. Clin.Oncol.(2009) 27:5138-5143.
Lancet (2009) 374:1243-1251.
Menopause (2012) 19: 260-261.
Subsequent Trial
KEEPS-USA (2012)
No increase risk of breast cancer with
estrogen alone
CV safety better with transdermal route
CVA risk related to higher doses
Progesterone has least effect on breast
proliferation, less than Provera.
NAMS 2012 Annual Meeting : KEEPS Report
NAMS
Authority for evidence based practice:
www.menopause.org
Position Paper HT 2012 Menopause 9:257-271.
Recommendations for Clinical Care of
Midlife Women 2014 Menopause 21:1038-1062.
Statement on HT Use after Age 65 2015
April 6, 2015 NAMS Position Statement.
Symptom Management
Hot flashes/ night sweats
Mechanism not fully understood
Estrogen withdrawal rather than low levels
SWAN study (ongoing):
2015 data shows max duration of hot flashes 12
years (average duration 7.4)
Hot flashes can continue 4.5 years after last
period
Int, J. Women’s Health (2010) 2: 123-135.
JAMA Internal Medicine online, Feb. 16, 2015.
Pharmacologic Rx: Hot Flashes
HT
FDA-approved
CBHT (Compounded Bioidentical HT)
SSRI/SNRI
Gabapentin (Neurontin)
Clonidine
Hormone Therapy
FDA Approved: (bioidentical)
Estrogens
Orals:
○ Estrace, generics
Patches:
○ Alora, Climara, Esclim, Estraderm Menostar, Minivelle,
Vivelle
Gel:
○ Divigel, Estrogel, Elestrin
Cream: Estrasorb
Spray: EvaMist
Vaginal ring: Femring
Progesterone
Oral: Prometrium, generic
Hormone Therapy
FDA Approved (not bioidentical)
Premarin
Prempro
Duavee (Conjugated estrogens 0.45mg
Bazedoxifene 20mg )
Other Agents
FDA Approved:
Brisdelle (Paxil 7.5mg)
Non-FDA Approved: (No FDA approved nonhormonal agents)
Paroxitine (Paxil) 12.5-25mg ($4.00)
Citalopram (Celexa) 10-20mg ($4.00)
Escitalopram (Lexapro) 10-20mg
Venlafaxine (Effexor) 37.5-75mg (BP)
Desvenlafaxine (Pristiq) 100-150mg (BP)
Other Agents
Gabapentin (Neurontin) 900-1800mg
○ Start with 300mg at night, increase by 300mg
till maximum effect reached
○ Side effects: weight gain, drowsiness
Clonidine (Catapres) 0.1mg
Side effects: sedation, bradycardia,
hypotension, dry mouth
Low Dose HT: Is Low Dose Safer?
FemHRT 2.5mg EE/0.5mg NETA
Activella 0.5mg E2/ 0.1mg NETA
ClimaraPro 0.045mg E2/0.015mg LVN
Oral E2 (Estrace) 0.5mg
Transdermal E2 0.014mg (Menostar) 0.025mg
Gel, Cream, Mist
Arch.Int.Med. (2008) 168: 861-866.
Eur HeartJ. (2008) 29: 2660-2668.
Is Bioidentical Progesterone Safer?
Progesterone
Favorable effect on HDL-C (PEPI)
Less risk for clot and Breast Cancer
probable (KEEPS Trial)
Not in any combination products
COMPOUNDED BIOIDENTICAL
HORMONES
1-2.5 million women currently using
86% unaware not FDA approved
27% don’t know if personalized or compounded
2.5 billion dollars/year
Compounding pharmacies accreditation, state
licensing
Poster 2014 NAMS Annual Meeting: Univ. VA. Health System
Progesterone
Estriol vaginal
TRANSDERMAL THERAPY
Less effect on
Draw backs
Clotting factors
Cost
Triglycerides
Limited E+P comb.
C-Reactive Protein
No bioidentical P
SHBG (testosterone)
Possible skin irritant
BP (probably)
Consistent blood levels
Multiple low doses
Bioidentical
Are Transdermals Safer?
VTE
Increased first VTE with oral vs. transdermal
CAD
Decreased risk MI with unopposed ET
CVA
Low dose only
BMJ (2008) 336: 1203-1204.
Circulation(2007) 115:840
BMJ (2010) 340:2519.
PERIMENOPAUSAL SYMPTOMS
Hormone Therapy
Risk/Benefit Assessment Tool
Page 1: Benefits
More benefit from
Hormone Therapy
+
-
+
-
Hot flashes
Night sweats, insomnia
Vaginal dryness, painful intercourse
Fuzzy thinking – noun, object forgetting
Skipped periods
Frequent periods
Palpitations/anxiety
Aching joints
Mood swings/irritability
Urethral relaxation/incontinence
OSTEOPOROSIS RISK
Age: over 60
Osteopenia/osteoporosis by DEXA
Non-traumatic fractures
First degree relative with fracture – hip or vertebra
Sudden loss of height greater than 11/2"
Small bones
Drugs:
anticoagulants
anticonvulsants
lithium
immunosupressives
thyroid unregulated
steroids
diuretics
SSRI > 1 year
alcohol – more than 2 per day
Caucasian/Asian
Low calcium intake
Low exposure to sun and vitamin D
Menopause prior to age 50
Malabsorption syndrome
Eating disorder, amenorrhea
Caffeine or soda excess
Sedentary lifestyle
Hormone Therapy
Risk/Benefit Assessment Tool
Page 2: Risks
CARDIOVASCULAR RISK
More risk from
Hormone Therapy
+
-
+
-
Age: over 50
CRP elevated
Homocysteine elevated
Sedentary lifestyle
Waist-hip ratio
HDL below 50
LDL over 130
Triglycerides over 150
First degree relative with heart attack before 50
Hypertension
Diabetes
Smoker
BREAST CANCER RISK
Age: over 54.5
Nulliparous
First pregnancy after 30
First degree relative
Breast density increased
Atypia by breast biopsy
Alcohol use in excess of 2 per day
Low vegetable and fruit diet, obesity
Lack of exercise
Radiation exposure
Menarche before 12
Menopause after 53
Active smoking
A free mobile app for menopause symptom management from
The North American Menopause Society
Clinical decision support tool
Available for iPhone and iPad
Dual mode for Clinicians and Women/Patients
Learn more at: Menopause 2015; 22(3):[e-pub 10/13/14] or at
www.menopause.org
Stopping HT
90% note recurrent VMS
Most try CAM alternative
Herbal preparations
Acupuncture
Behavioral/ Lifestyle modification
Many use SSRI/SNRI
50% return to HT low dose
Menopause (2015) 22:384-390
SSRI/SNRI for Hot Flashes
Mechanism:
○
○
○
○
Estrogen withdrawal
Decreased norepinephrine and seratonin levels
Increased receptors in hypothalmus
Narrowed setpoint in thermoregulatory nucleus
SSRI/SNRI increase endorphin levels, have
potential to decrease hot flashes by up to 65%
SSRI/SNRI use after 1 year can decrease bone
density, increase fracture risk
Int. J. Women’s Health (2010) :123-135.
Pharmacotherapy (2009) 29: 1357-1374.
SSRI/SNRI for Hot Flashes
Best choices:
○ Citalopram (Celexa)
○ Escitalopram (Lexapro)
○ Paroxetine (Paxil)
Tend to be less effective:
○ Fluoxetine (Prozac) 10-20mg ($4.00 for 30 days)
○ Sertraline (Zoloft) 25-100mg
Note: SSRIs interfere with Tamoxifen MOA
○ in this case use SNRI (venlafaxine/Effexor;
desvenlafaxine/Pristiq; duloxetine/Cymbalta)
These decrease bone density after I year
Re-evaluate efficacy after 12 months
Strategies
Lifestyle modification
Keep core body temperature cool
○ Dress in layers
○ Avoid:
Hot rooms
Hot drinks
Spicy food
Alcohol
Caffeine
Sugar
White flour
Cigarette smoke
Strong emotions
Strategies
Regular exercise
British study reduction in alterations in sleep and
mood, but not VMS
Swedish studies indicate reduction in hot flashes
SWAN does not show any reduction
○ ? Self-selection bias - healthy lifestyle
Menopause (2015) 22:384-390
Maturitas (2004) 48: 97-105
Am J Epidemiol (2000) SWAN
Paced breathing
Slow deep abdominal breathing at onset of hot flash
Menopause (2004) 11: 11-33
Strategies
Other
Some benefit shown in latest British trials:
-
Massage
Meditation
Yoga
Biofeedback/CBT/mindfulness
Mediterranean diet
Acupuncture
-
Improves VMS frequency and severity
Menopause (2015) 22: 384-390
Menopause(2008) 15:1070.
Strategies
Soy foods/isoflavones
○ 1 to 2 servings soy food per day
40-80 grams soy protein
80-120 grams isoflavones
○ Tofu, tempeh, soy milk, roasted soy nuts
○ Allow 1 month to determine effect
Menopause (2015) 22; 185-197
Soy Studies
Isoflavones don’t stimulate growth of
endometrium in post-menopausal women
J Soc Gynecol Investig (2002) 9: 238-42
Menopause 2015; 185-197
Hot flash incidence does not correlate with
serum levels of phytoestrogens, daidzein,
and equol, but does with genistein.
Other components of soy may be
responsible for reduction in hot flashes
Obstet Gynecol (1999) 94: 229-231
Am. J. Clin. Nutr. (2014)100; 4233-4305.
Soy Studies
Conversion of daidzein to equol
Intestinal bacteria (equol producers)
Equol producers may derive greater soy benefit
S-EQUOL
Swedish flower pollen extract
Contains low sub effective concentrations of daidzin,
daidzein, and genistein
○ No estrogenic or phytoestrogenic activity
FEMAL
RELIZEN
Menopause (2011) 18:732-753.
Soy Studies
Soy improvement of cognitive function
No evidence of harm 60-160mg 6wk-30mo.
Improvement of summary cognitive function
and visual memory
Earlier in age of initiation helps
Menopause (2015) 22: 198-206.
Soy Studies: Estrogenic?
Preliminary Studies
In premenopausal women soy
phytoestrogens may have an antiestrogen effect since soy isoflavones
displace endogenous estrogen from
receptors.
Daily soy consumption lowers circulating
levels of estradiol over the entire
menstrual cycle by 20%.
J Clin Endocrinol Metab (2001) 86: 3045-3052
Soy: Prevention of Breast CA?
Review of 18 human studies showed no
protective effect of phytoestrogen
consumption with possible exception of
women consuming them during
adolescence or at very high doses.
Isoflavones may enhance early cellular
differentiation and maturation of mammary
glands making them less susceptible to
carcinogens.
Breast Cancer Res Treat (2003) 77: 171-183
Am.J.Clin.Nutrition (2014) 100: 423s-430s.
Adverse Effects: Soy
GI upset
Allergy
More research is needed to define the
role of soy in breast cancer.
Influence of genetic modification a
factor.
Soy does not seem to have a
proliferative effect on endometrial cells.
Contraindications: Soy
Allergy (Risk higher if asthma or allergic
rhinitis)
Relative contraindications
Estrogen dependent cancer
(however, it may turn out to be protective)
Interactions: Soy
Preliminary evidence soy isoflavones
antagonize anti-tumor effects of
Tamoxifen
Ann Pharmocother (2001) 35: 1118-1121
1 case report: Soy milk decreased INR
in a patient taking warfarin. Mechanism
not known
Ann Pharmocother (2002) 36: 1893-1896
High intake of soy in postmenopausal
women may lower PTH levels
Other Herbal RCTs
Black Cohash
Discontinue after 6 months
Possible liver damage
MACA/ Femenessence
Red Clover/Promensil
Estroven
Combination of herbs
Progesterone Cream
Multiple preparations-some with no active
progesterone
400 mg P4 in 2 oz. cream-20 mg/Gm
No adverse effects
Will not prevent estrogen-induced
endometrial hyperplasia
Study outcomes conflict- NAMS does not
recommend for hot flash relief
Obstet Gynecol (1999) 94: 225-228
Menopause (2003) 10: 13-18
Menopause (2004) 11: 11-33
Bone Density Loss
2-5%/year first 5 years after FMP
Increased loss after age 65
Diagnosis made by:
DXA Spine and Hip T-score >2.5
Fragility fracture
DXA at age 65 unless other risk factors
BMI < 28 best predictor but not used alone
First degree relative with fracture
Absence of menses with low body weight
Osteoporosis Int. (2011) 22: 517-527.
Bone Density Loss
FRAX score
Used to evaluate risk of fracture even
without DXA
Web-based tool (WHO)
Helps in decision to treat to prevent fracture
Based on 10 year probability of fracture
○ Hip 3% or higher
○ Major osteoporosis-related fracture 20% or
higher
Bone Density: Prevention of Fracture
Bone-resistant exercise 30min. 3x/week min.
with weight regimen
Calcium 1200-1500mg/day, maximum
1000mg in supplement, most in foods that
also have minerals to help absorb (Vit. K2)
Vitamin D3 to achieve serum level of 4060ng/dl
○ Up to 5000IU/day (controversial)
○ Unblocked sun 10-15 min. upper body 3-
4x/wk =10,000IU
Bone Density: Prevention of Fracture
Vitamin K2
Found in green leafy vegetables (kale, chard)
Controversial doses 40-200mg/day
Balance
Yoga, Tai Chi, Qi Gong
Fall prevention
Rugs, safety rails, lighting, alcohol limits
Smoking cessation
Body weight over 127 lb or BMI >28
SSRI/SNRI / thyroid treatment adjustment
Bone Density: Prevention of Fracture
Bisphosphonates
Have been over used and used in women too young
Controversial over duration and length of holiday
Recommend 5 years on, 5 years off with re-
evaluation
3months off before jaw procedure with 3 months to
allow for healing
Remain first line of treatment for women over 60 or
who can not take HT
Must take on empty stomach ½-1hour before eating
with 8 oz. water and stay upright.
Climacteric (2014) 17:4-7.
Bone Density: Prevention of Fracture
Pharmacologic Prevention
FDA Approved for prevention
○ Estrogen or HT especially if under 60 years of age
○ Menostar 0.014mg patch/ annual progesterone
○ Brisdelle (CEE 0.45mg with bazodoxiphene
20mg)
Prevention and Treatment
○ Raloxifene (Evista) 60 mg
Spine only
Can increase risk of VTE, CVA , VMS
Never double up HT with another agent
Bone Density: Fracture Treatment
Osteoporosis
○ Denosumab (Prolia) 60mg subq q6mo.
$2016.00
○ Teraparatide (Forteo) 20 mcg subq qd
$18.720.00
○ Zoledronic Acid (Reclast) 5mg IV over 15 min.
yearly $1301.00
○ Calcitonin 200 IU nasal spray (alt. nostril) daily
In FDA pipeline
Blosozumab subq inj. Q2-4 wk (+18%/yr)
Odancatib (+12%/yr)
Bone Density: Fracture Treatment
Alendronate (Fosamax) $12.00
Binosto (effervescent Fosamax: 650mg NA=1650mg
Nacl) $245.
Residronate (Actonel) $233.00
○ Increased loss after discontinuing
○ Easier on GI system
Ibandronate (Boniva) $139.00
○ Not yet FDA approved
○ IV push 3mg q3mo. $2108.00
Bone Density: New Guidelines
DXA frequency
Low-risk, wait till 65yo
With risk 6-12 mo after FMP
○ If T-score -1 to <-1.5 repeat 10 years
○
○
-1.5 to <2
-2 to -2.5
repeat 5 years
repeat 2 years
Genitourinary Syndrome of Menopause (GSM)
Term replaces atrophic vaginitis, vulvovaginal
atrophy and all terms related to vulvar and
urinary symptoms associated with menopause
including urgency, atrophic dysuria, recurrent
UTIs
Vaginal health prescription (as with exercise
prescription)
○ Daily activities, hygiene
○ Prescription meds
○ OC options
○ Physical therapy
○ Sexual issues
Dyspareunia
Rule out chronic infection/inflammation
○ STIs
○ Provoked vulvar pain
Culture chronic symptoms, negative wet mount
Re-establish lactobacilli to normalize
pH 4.5-5.0
Insure adequate lubrication
Vaginal Aging Questionnaire (DIVA)
Self-administered
Assesses impact of vaginal symptoms on
functioning
Menopause (2015) 22: 144-154.
Dyspareunia
Re-establish epithelial maturation: local estrogen
Conjugated equine estrogen cream (Premarin)
Estradiol cream (Estrace)
Femring
○ Necessitates adequate progestogen opposition
○ Questionable effect on breast tissue
Estring (estradiol) 7.5 mg 1q 3 mo
Vagifem (estradiol) 0.025 mg 1 2x/week*
Ospemifene (Osphena) 60mg po/day
○ Systemic SERM should not need progestogen
E3 Estriol 0.5 mg/Gm 1 Gm 2x/week *
*After loading dose of qhs x 14
NAMS petitioning FDA to remove Black Box warnings (2014)
○ Negligible systemic absorption
ObstetGynocol.(2008) 111:67-76.
Menopause(2014) 21:911-916.
VAGINAL LASER TREATMENT
3 five to ten minute treatments q 4-6
weeks
$750-$1000/treatment
No long-term safety data
Potentially dangerous scarring
Web event: NAMS: Treatment of GSM; April 16, 2015.
Decreased Libido/Sexual Dysfunction
Assess physical, psychological, social factors,
relationship issues;
Evaluate possible side effects of medications,
herbs, OTC products.
Effect of serum hormone levels: (day 3-5 level
of cycle)
Estrogen not related to any measure of sexual
function
Testosterone influences masturbation, sexual desire,
and arousal
FSH influences masturbation, arousal, and orgasm
BSO leads to 50% less testosterone
J.Clin.Endoc.Metab. (2014) 99: 3489-3510.
Pharmacologic Interventions
Consider alternatives to medications
contributing to side effects decreasing
libido
Androgen therapy (2006 Guidelines: no
indication for androgen Rx)
Play a role in regulating lean muscle mass,
energy level, libido, and sense of well-being
in women
Modulate breast growth and development
Trends Endocrinol Metab (2001) 12: 33-37
Decreased Libido
2014 Guidelines (Endocrine Soc. Task
Force)
Recommend against making a diagnosis for
androgen deficiency syndrome in healthy
women because data are lacking
Against routine use of DHEA
Hypoactive sexual desire-evidence supports
short-term physiologic doses of testosterone
J.Clin.Endocrinol.Metab. (2014) 99:3489-3510.
Decreased Libido
Epidemiologic evidence/androgens in the
development of breast cancer
Based on single samples of hormone levels
No control for variables e.g. time of day, diet,
body mass, activity
Assays not sensitive enough in women
Aromatize to estradiol in tissue
PCOS: no increase in breast cancer rates
No increase in 6 mo. Patch trials
Decreased Libido: Treatment
Could androgens play a protective role in
breast cancer?
Testosterone: genetic studies-the lower the
testosterone the higher the incidence of breast
cancer
Breast Cancer Res (2003) 5: 164-173
DHEA: lower risk of breast cancer at high
estrogen concentrations; higher risk of breast
cancer at low estrogen concentrations
Endocr Rev (2003) 24: 152-182
Androgens: Rhesus monkeys
Endogenous androgens reduce mammary
epithelial proliferation
FASEB J (2000) 14: 1725-1730
Decreased Libido: Treatment
No FDA approved androgen-alone product
Estratest- shows improvement in libido
Clinical Therapeutics (1997) 19: 383-404
Sildenafil (Viagra) @ 10, 50 and 100 mg did not
improve sexual response. Higher doses were
related to headaches and flushing.
BJOG (2001) 108: 623-628
Canada
Methyl testosterone (Metandren) po
Testosterone undecancate (Andriol) po
Testosterone enanthate (Climacteron, Delatestryl) IM
Decreased Libido: Treatment
Topical methyl testosterone
Compounding pharmacies including mail away
insurance pharmacies
Methyl testosterone 5 mg/Gm 0.5 gm/day
○ Androgel Testoderm
Not FDA approved
Topical testosterone
Patch- (Intrinsa) no longer being manufactured
Compounding pharmacies “Oprah Winfrey
Prescription” 1% testosterone cream (10mg/Gm)
0.5Gm qhs – no data on safety or efficacy –Goal to
stay within normal levels for women.
Patch data 300mcg (3mg) day, normal serum levels
Libigel (Phase III trials) 300mcg/day
Decreased Libido: Treatment
Testosterone side effects
Hirsuitism
Acne
Alopecia
Dark coarse hair will grow where cream applied
Clitoris will enlarge with topical application
Libido-enhancing effect may be lost at higher doses
Elevated mood may result in depression with sudden
withdrawal
No data available for over two years’ use
Decreased Libido: Treatment
DHEA
OTC products often do not contain amount specified
on label
Oral DHEA converts more to estrogens
Topical DHEA converts mostly to testosterone
J Clin Endocrinol Metab(1999) 84: 3896-3902
No benefit as an anti-obesity drug or anti-aging drug
Contraindicated in women of reproductive age:
masculinization of female fetus
Contraindicated in women with hormone- responsive
tumor
At 25-50 mg/day appears to be well tolerated in older
women
Banned in Canada due to lack of safety data
Decreased Libido: Treatment
Intravaginal DHEA
Urogenital atrophy
Decreased libido
6.5mg suppository qhs
12 week RCT
○ Improved vaginal cytology
○ Decreased pH
○ Improved dyspareunia
○ Did not elevate circulating hormones over
placebo.
Climacteric (2011) 14: 282-288.
Decreased Libido:
Non-pharmacologic Interventions
Establish regular sexual contact,
allowing 1-2 hours
Change routine, include erotic material,
sex toys
Explore non-coital activity
Consider seeing sex therapist
PATIENT # 1
E.W. 54yo, 3years since FMP
○ Persistent hot flashes during the day
○ Occasional night sweats, goes back to sleep
○ Type II diabetes
○ Borderline hypertension
○ Family history of osteoporosis
○ Dyspareunia
Best friend just started HT and wants you to
order it for her as well.
PATIENT # 2
51yo skipping cycles, LMP 3 months ago
Hot flashes come, then go
Feeling sleep-deprived
History of postpartum depression, feeling “down”
BMI 18, skipped cycles with anorexia as teen
MGM with breast cancer at age 68, normal
mammograms
Wants symptom relief
Conclusion
Assess all patient’s strategies including herbal
preparations when taking a history
Effective v. not effective or no data
Inform patient about lack of standardization
among over the counter products as well as
side effects and interactions
Evaluate individual risk/benefit ratio for any
suggested therapeutic intervention
Encourage modification of risk factors
contributing to CVD or Breast Cancer that
often outweigh risk posed by short-term HT
“It is much more important to know what sort of
patient has these symptoms than what sort
of symptoms a patient has.” Sir William Osler