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LeighAnn Frattarelli, MD, MPH
February 3, 2018
State North American Menopausal Society (NAMS)’s position on hormone therapy
Be familiar with newer treatments for ◦ Vasomotor symptoms of menopause (VMS)
◦ Genitourinary symptoms of menopause (GSM)
.
75 to 80 percent of menopausal women in the US
Study of Women across the Nation (SWAN):
Median total VMS duration was 7.4 years, persisting
median of 4.5 years after the final menstrual period
(FMP.)
Premenopausal or early perimenopausal when first
experienced VMS longest total duration (>11.8 years.)
Probability of VMS: Average observed probability of VMS at each time point within each trajectory subgroup. No factors were included in the model.
From: Tepper PG, Brooks MM, Randolph JF, et al. Characterizing the trajectories of vasomotor symptoms across the menopausal transition. Menopause 2016 23:1067.
Key points from the
2017 Position Statement of
The North American Menopause Society
© 2017
Menopause. 2017 Jul;24(7):728-753.
The 2017 NAMS Hormone Therapy Position
Statement has been endorsed by
Academy of Women’s Health
American Association of Clinical
Endocrinologists
American Association of Nurse Practitioners
American Medical Women’s Association
American Society for Reproductive Medicine
Asociación Mexicana para el Estudio
del Climaterio
Association of Reproductive Health
Professionals
Australasian Menopause Society
Chinese Menopause Society
Colegio Mexicano de Especialistas
en Ginecologia y Obstetricia
Czech Menopause and Andropause Society
Dominican Menopause Society
European Menopause and Andropause Society
German Menopause Society
Groupe d’études de la ménopause
et du vieillissement Hormonal
HealthyWomen
Indian Menopause Society
International Menopause Society
International Osteoporosis Foundation
International Society for the Study of Women’s Sexual
Health
Israeli Menopause Society
Japan Society of Menopause and Women’s Health
Korean Society of Menopause
Menopause Research Society of Singapore
National Association of Nurse Practitioners
in Women’s Health
SIGMA Canadian Menopause Society
SOBRAC and FEBRASGO
Società Italiana della Menopausa
Society of Obstetricians and Gynaecologists of Canada
South African Menopause Society
Taiwanese Menopause Society
Thai Menopause Society
The American College of Obstetricians and Gynecologists supports the value of this clinical document as an
educational tool, June 2017. The British Menopause Society supports this Position Statement.
No evidence to recommend discontinuation after age 65 if
indication remains and no contraindications
Breast cancer risk does not increase appreciably with short-
term use of estrogen-progestogen therapy and may be
decreased with estrogen alone
No increased risk of breast cancer in women who are BRCA-
positive on hormone therapy after risk-reducing bilateral salpingo-oophorectomy
© 2017
Benefits are likely to outweigh risks for
symptomatic women who initiate hormone therapyage <= 60 years
or within10 years of menopause onset
(Level I)
© 2017
The 2017 hormone therapy position statement of The North American Menopause Society.
Menopause. 2017;24(7):728-753.
Low-dose vaginal estrogen therapy (ET)◦ Minimal systemic absorption
Blood levels in postmenopause range
◦ Based on limited data, minimal risk for recurrence of breast cancer (Level II)
For survivors of breast cancer with bothersome genitourinary
syndrome of menopause symptoms, low-dose vaginal ET
may be an option◦ After a failed trial of nonhormone therapies
◦ In consultation with an oncologist
◦ Concern even with low-dose vaginal ET for women on aromatase inhibitors
because of suppressed estradiol levels (Level III)
© 2017
The 2017 hormone therapy position statement of The North American Menopause Society.
Menopause. 2017;24(7):728-753.
Randomized, double-blinded, placebo-controlled, multicenter trial
Test whether estrogen-replacement therapy slows progression of atherosclerosis when begun within 36 months of the last menstrual period
727 KEEPS participants: 42 to 58 years old (mean, 52.7 years) and within 36 months of the last menstrual period at enrollment
Many favorable benefits (results beginning 2012)
The women with symptoms appeared to have quality-of-life benefit and an overall favorable benefit:risk ratio
Transdermal estrogen, but not oral, associated with improvement in sexual function scores
KEEPS Taylor HS, Tal A, Pal L, et al. Effects of oral vs transdermal estrogen therapy on sexual function in early postmenopause: ancillary study of the Kronos Early Estrogen Prevention Study (KEEPS) [published online ahead of print August 28, 2017]. JAMA Intern Med.
Prescription rates for custom-compounded bioidentical hormones approach those of US Food and Drug Administration (FDA)-approved MHT prescriptions
Importance of physician and patient education about the differences
Bazedoxifene: estrogen agonist and antagonist. Agonist on bone and antagonist effects on the endometrium.
Duavee FDA indicated for postmenopausal women for treatment of moderate to severe vasomotor symptoms and prevention of osteoporosis (2013)
Phase III Trials: Selective Estrogen, Menopause and Response to Therapy (SMART) Progams:
Significantly reduced number of hot flashes by 74% (47% placebo) and severity by 39% (13% placebo)
Increased BMD at hip and spine at 1 and 2 years
Common Side Effects (5-9%)
◦ Muscle spasm
◦ Nausea
◦ Diarrhea
◦ Upset stomach
◦ Abdominal pain
◦ Throat pain
◦ Dizziness
◦ Neck Pain
Benefits◦ Similar rates of amenorrhea as placebo (87%)
◦ Lower rates of breast pain compared to EPT (5-8% vs 20-24%)
◦ No increase in breast density
Differential effects of menopausal therapies on the endometrium. MirkinS, et al; Menopause. 2014;21(8):899
50% to 80% of North American women use nonhormonal therapies for VMS at midlife
©2015
North American Menopause Society. Menopause. 2015;22(11).
North American Menopause Society. Menopause. 2015;22(11).
FDA-approved 7.5mg paroxetinesalt (Brisdelle)
Other SSRIs and SNRIs yielding significant VMS reductions in large RCTs
Gabapentin and pregabalin
©2015
FDA approved 2013
Paroxetine 7.5mg a day
Up to 60% decrease in hot flashes
Not for use with Tamoxifen: Strong inhibitor in CDYP2D6
Large RCTs show significant VMS reductionswith—Paroxetine—Escitalopram—Citalopram—Venlafaxine—Desvenlafaxine
North American Menopause Society. Menopause. 2015;22(11). ©2015
North American Menopause Society. Menopause. 2015;22(11).
Start lowest dose first; titrate up to effect, tolerance
When stopping, taper therapy over 1-2 wk
Re-evaluate carefully and regularly (eg, every 6-12 mo)
©2015
Level II evidence suggests these may be beneficial Weight loss Mindfulness-based stress
reduction S-equol derivative of soy Stellate ganglion block
North American Menopause Society. Menopause. 2015;22(11). ©2015
Do not recommend
North American Menopause Society. Menopause. 2015;22(11). ©2015
Level I evidence shows these are unlikely to alleviate VMS, although they may have other health benefits Exercise Yoga Paced respiration Acupuncture
Vaginal lubricants and moisturizers— Should be considered first-line
therapies— Over-the-counter products can
significantly decrease or eliminate symptoms for many women
Herbal products have not demonstrated any beneficial effect in clinical trials
North American Menopause Society. Menopause. 2013;20(9):886-904. ©2013
North American Menopause Society. Menopause. 2013;20(9):886-904.
US FDA-approved vaginal ET products
— Estradiol vaginal cream (Estrace)a:
— Conjugated estrogen vaginal cream (Premarin)a
— Estradiol vaginal ring (Estring)
— Estradiol acetate vaginal ring (Femring)b
— Estradiol hemihydrate vaginal tablet (Vagifem) and generic
Generic Estradiol vaginal cream approved 2017
©2013
aMultiple doses available; use low dose for VVA.bThis product delivers systemic levels of estradiol.
Typically provides greater benefit than nonhormonal interventions
Preferred mode of delivery when vaginal symptoms are the only complaint
Shown in clinical trials to be more effective than systemic oral ET
May also reduce risk of urinary urgency and recurrent urinary tract infections
North American Menopause Society. Menopause. 2013;20(9):886-904. ©2013
Ospemifene: Osphena
North American Menopause Society. Menopause. 2013;20(9):886-904. ©2013
Nonhormonal selective estrogen-receptor modulator (SERM)
Only SERM approved in the United States to treat moderate to severe dyspareunia
Ospemifene: Effectiveness
North American Menopause Society. Menopause. 2013;20(9):886-904. ©2013
Two 12-week studies showed improvements with daily use (60 mg) in— Vaginal maturation index — Vaginal pH— Most bothersome symptom (vaginal
dryness) 52-week extension study showed
sustained improvements with no casesof venous thromboembolism, endometrial hyperplasia, or carcinoma
Ospemifene: Adverse effects
North American Menopause Society. Menopause. 2013;20(9):886-904. ©2013
Vasomotor symptoms most common
Prescribing information contains precautions similar to those for estrogens and other SERMs
Data in women with breast cancer or at high risk of developing breast cancer are lacking
Intracrinology: Aromatization at the cellular level to estrone and estradiol
At 12 weeks, significant increase from baseline in serum DHEA, testosterone, and estrone, but not estradiol levels
DHEA, estradiol, estrone, and testosterone remained within the range of an average postmenopausal women [76].
Approved by FDA Nov 2016
Vaginal discharge most common side effect
12 week trials 665 women
5.7% vaginal discharge Intrarosa vs. 3.7% placebo
Non-comparative study 521 participating: 74 cases of vaginal discharge (14.2 percent)
Comparison of intravaginal 6.5mg (0.50%) prasterone, 0.3mg conjugated estrogens and 10μg estradiol on symptoms of vulvovaginal atrophy
Concluded AT LEAST as effective as 0.3mg vaginal CEE and 10mcg estradiol
◦ J Steroid Biochem Mol Biol. 2017 Nov;174:1-8. doi: 10.1016/j.jsbmb.2017.03.014. Epub 2017 Mar 18.
Effect of Intravaginal Prasterone on Sexual Dysfunction in Postmenopausal Women with Vulvovaginal Atrophy.
Randomized placebo controlled trial: all the six domains of the Female Sexual Function Index (FSFI) improved over placebo (from P = 0.047 to 0.0005)
Labrie F, et al; Journal of Sexual Function 2015
Overall satisfaction with sexual life significantly improved (p < 0.001).
Seventeen (85%) out of 20 (26%) women, not sexually active because of VVA severity at baseline, regained a normal sexual life at the 12-week follow-up.
Significant improvement in each VVA symptom (p < 0.001) and in quality-of-life evaluation, both for the scores in the physical (p = 0.013) and mental (p = 0.002) domains.
Salvatore, S. Climacteric, 2015
Significant improvement in VVA symptoms (vaginal dryness, burning, itching and dyspareunia) (P<0.0001)
VHI scores were significantly higher at T1 (P<0.0001)
Overall, 91.7% of patients were satisfied or very satisfied with the procedure and experienced considerable improvement in quality of life (QoL)
No adverse events due to fractionalCO2 laser treatment occurred.
Perino A. Maturtis, 2015
Proof of Concept Study
Funded by the Medical Research Council and the National Institute for Health Research (NIHR)
Significantly reduced menopausal flushing by 73% during a four-week treatment period