What’s new in Menopausal
Medicine
Erica Johnstone, MD
Feb. 9, 2015
Objectives
• Review innovations in the management of
menopause and perimenopause in the past 2
years
• Understand the North American Menopause
Society Recommendations for Clinical Care of
Midlife Women and their implications
New Products: DuaVee
• Conjugated estrogens 0.45 mg/Bazedoxifene 20
mg tablets
• Bazedoxifene is a SERM, originally developed,
but not FDA-approved for osteoporosis
• Alternative to progestin to prevent endometrial
hyperplasia or cancer
New Products: DuaVee
• FDA approved October 2013
• Indications:
▫ Moderate to severe vasomotor symptoms
associated with menopause
▫ Prevention of menopausal osteoporosis
DuaVee: Effectiveness
• Mean reduction in hot flashes of 2.7 per day
greater than placebo at 12 weeks
• 1.6-1.7% increase in lumbar spine bone mineral
density at 24 months, compared with 1.5-2%
decrease in placebo groups
DuaVee: Risks
• 0.7% incidence of endometrial hyperplasia or
malignancy at 24 months
• Postmenopausal bleeding did not differ from
placebo
• No apparent increase in VTE, stroke, or CHD
over placebo at 24 months
• Presumed to have the same safety profile as ERT
based on WHI data
New Products: Brisdelle
• Paroxetine 7.5 mg qhs
• Lower dose than used for major depressive
disorder (10-60 mg daily)
• Reduction in moderate and severe hot flashes by
0.9 to 1.7 per day compared with placebo in 2
RCTs
• Interaction with tamoxifen lowers tamoxifen
effectiveness
Simon et al, 2013
Preliminary data from the ELITE Trial
• Early versus late Intervention Trial of Estrogen
• 643 postmenopausal women
▫ Half menopausal <6 years
▫ Half menopausal >10 years
• 1 mg 17 beta-estradiol versus placebo.
• 10 days per month of micronized progesterone vaginal
gel or placebo for women with a uterus
• Early intervention group using estrogen had slower
progression of atherosclerosis measured by carotid IMT
than the women randomized to placebo.
• No difference based on estrogen in the late intervention
group.
• P value for interaction was .007.
North American Menopause Society
Recommendations: Contraception
• Low dose oral contraceptives are appropriate for
heavy menstrual bleeding and irregularity in
perimenopause (Level I)
• Contraception should be continued until 12
months of amenorrhea (Level I)
NAMS: Treatment of Vasomotor
Symptoms
• Hormone replacement therapy
• Brisdelle (paroxetine 7.5 mg) is FDA approved
• Other SSRIs with demonstrated efficacy include
paroxetine, escitalopram, venlafaxine, and
desvenlafaxine; paroxetine
• Gabapentin and clonidine reduce hot flashes but
have not been approved by FDA for this
indication.
NAMS: HRT
• A prolonged course of HRT can be considered
for treatment of symptoms or osteoporosis if
alternatives are not appropriate (Level III)
• HRT is recommended for women with early
menopause or primary insufficiency until age 52,
and longer durations can be considered to treat
symptoms. (Level II)
NAMS: Bioidentical HRT
• Compounded HRT is not receommended due to
concerns about quality, safety, and efficacy
(Level I)
• Neither serum nor salivary hormone levels are
recommended to monitor therapy for
menopausal symptoms. (Level II)
• Prescription of FDA-approved natural products
(estradiol, progesterone) is recommended for
women who prefer bioidentical HRT (Level II)
A Reminder…
• Hormone replacement therapy does not prevent
or treat cardiovascular disease
• Cardiovascular effects of HRT are more
favorable in women 50-59 years and within 10
years of menopause when treatment is initiated
(Level I)
NAMS: Genitourinary Syndrome of
Menopause
• Low-dose vaginal estrogen is effective and does
not require progestin therapy. (Level I)
• The estrogen agonist/antagonist ospemifene is
an oral agent for the treatment of moderate to
severe dyspareunia due to GSM/VVA. (Level I)
• Postmenopausal women with recurrent UTIs
may consider treatment with low-dose vaginal
ET or prophylactic antibiotics. (Level I)
NAMS: Sexual Function
• Bupropion and PDE-5 inhibitors may have a role
in the treatment of SSRI-induced sexual
dysfunction. (Level II)
• No role for DHEA
NAMS: Androgen Therapy
• Testosterone therapy may benefit some
postmenopausal women with female sexual
interest/arousal disorder, but there are no
formulations available for women in the US and
inadequate long-term safety (Level I)
• Monitoring of testosterone therapy should include
assessment of facial hair, acne, virilization, and
adverse changes in lipids or liver function tests.
• Blood testosterone levels should be maintained in
the normal range for reproductive-aged women.
(Level II)
NAMS: Hair loss and hirsutism
• First line for FPHL: Topical minoxidil 5% (FDAapproved)
• Limited evidence supports addition of an
antiandrogen (spironolactone) (Level II)
• Hair loss is not an indication for HT use (Level
II)
• Ketoconazole 2% and zinc pyrithione 1%
shampoos may increase scalp hair growth.
(Level II)
NAMS: Weight gain and obesity
• Mean weight gain across menopause is 5 lb (2.3
kg)
• Consider medical treatment in addition to diet
and exercise in women with a BMI greater than
30 kg/m2 or BMI greater than 27 kg/m2 with
comorbidities (Level II)
• Consider bariatric surgery in women with a BMI
of 40 kg/m2 or higher or a BMI greater than 35
kg/m2 with comorbidities who have failed
conservative measures. (Level II)
NAMS: Migraines
• Hormone therapy at standard doses is
appropriate for postmenopausal women with
migraines, but may worsen headaches in some
women
• Continuous rather than cyclic HT is
recommended as changes in hormone levels may
trigger a headache (Level II)
NAMS: Breast cancer
• Combined HRT increases breast cancer risk
beyond 3-5 years
• ERT does not increase breast cancer risk in the
first 7 years, but may thereafter
• SERMs (tamoxifen, raloxifene) reduce the
incidence of primary breast cancer in high-risk
women.
• Bazedoxifene effects on breast cancer risk not
yet adequately studied
NAMS: Soy and phytoestrogens
• Soy isoflavones may protect against breast
cancer during breast development.
• Soy isoflavones in early menopause may inhibit
the progression of atherosclerosis.
• Soy isoflavones and phytoestrogens are not
known to increase the risk of breast or
endometrial cancer, but women with breast or
endometrial cancer are advised to discuss their
use with their oncologist. (Level II)
NAMS: Supplements
• OTC topical progesterone cream does not
provide endometrial protection or benefit for
menopausal symptoms (Level III)
• Oral DHEA has not been shown to improve
mood, sexual function, or general well-being
(Level III)
• Melatonin may help with circadian-rhythm sleep
disorders (Level II)
References
• Hodis HN, et al. Testing the menopausal hormone
therapy timing hypothesis: The early versus late
intervention trial with estradiol. AHA 2014; Abstract
13283.
• Shifren L, Gass MLS, for the NAMS Recommendations for
Clinical Care of Midlife Women Working Group. The North
American Menopause Society Recommendations for
Clinical Care of Midlife Women.
Menopause 2014;21(10):1038-1062
• Simon JA, et al. Low-dose paroxetine 7.5 mg for
menopausal vasomotor symptoms: two randomized
controlled trials. Menopause 2013 Oct;20(10):1027-35.
doi: 10.1097/GME.0b013e3182a66aa7.
• Duavee Prescribing Information