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Managing Medically and Naturally

Mindy Goldman, MD Clinical Professor Dept. of Ob/Gyn and Reproductive Sciences Director, Women’s Care Program, UCSF Breast Care Center and Women’s Health University of California, San Francisco

I have nothing to disclose

–Mindy Goldman, MD CASE STUDY

50 yr. old G2P2 peri-menopausal woman presents with complaints of significant night sweats interfering with her ability to sleep. She has mild hot flashes during the day. She has never had a bone density test but her mother had a hip fracture at age 62 due to . Her 46 yr. old sister was diagnosed with breast cancer at age 43, treated with lumpectomy and radiation and currently is doing well. There is no other family history of cancer.

Questions

 1. Would you offer her MHT?

 2. If yes, how long would you continue it?

 3. If no, what would you offer for alternative treatments?

 4. Would your treatment differ if you knew she had underlying heart disease? Is it safe? How long can I take it?

What about Mymy Bones?bones?

Will it protect my heart?

MHT - 2015 What about my brain?

Will I get breast cancer? What about my hot flashes?

Menopausal Symptoms

 Hot flashes

 Night sweats

 Sleep disturbances

 Vaginal dryness/Sexual dysfunction

 Mood disturbances How to Treat Menopausal Symptoms

 Hormone therapy

 Alternatives to hormones

 Complementary and Integrative Techniques

Prior to Women’s Health Initiative

 Hormone therapy primary treatment of menopausal hot flashes

 Few women would continue hormones past one year

 By 1990’s well known that progestins protect against uterine cancer, so women with a uterus prescribed HRT and women with prior hysterectomy prescribed ERT

 Hormone therapy primary treatment of osteopenia and osteoporosis Prior to Women’s Health Initiative

 Vast majority of observational studies showed hormones protected against heart disease, so women with cardiac risks most often prescribed HRT/ERT (primary prevention)

 Many women took hormones for protection against Alzheimer's Disease

 Were the benefits of HRT/ERT overestimated?

Women’s Health Initiative – What was it

Prospective primary prevention RCT – designed to see if hormones protected against heart disease

 Hormone Therapy Trial (HT) (27,347)  Dietary Modification Trial (DM) (48,835)  / D Supplementation Trial (CaD) (36,282)  Observational Study (OS)  RCT/OS Participants: – From 40 Clinical Centers (CC) nationwide – 161,808 women aged 50-79; 68,132 in RCT 93,676 in OS

10 – 17.5% overall minority recruitment: Women’s Health Initiative – What was it

. Women with a uterus randomized to CEE .625 plus 2.5 medroxyprogesterone acetate vs. (prempro)

. Women with hysterectomy randomized to conjugated equine .625 vs. placebo (premarin)

. 16,000 women enrolled in CEE + MPA vs. placebo

. 11,000 in the CEE vs. placebo

. Average age 63 (range 50 -79 years)

. 10% of subjects were 50 to 54 years old

. 16% of subjects were less than 5 years past the onset of menopause

WHI – Study characteristics

 At entry, 7.7% had prior CVD

 36% had hypertension

 49% were current or past smokers

 34% had a body mass index ≥30

 Was not designed to study effects on menopausal symptoms WHI – What Happened

 Combination HRT study terminated early in May 2002 because of increased risk of breast cancer, heart attacks, stroke and DVT

 Study of Estrogen only did not find an increased risk of breast cancer and continued. It terminated 1 year early in 2004 because of an increased risk of stroke and no protection for heart disease

WHI: In Graphic - Numerical Terms

14 Gold Standard – but Criticisms of WHI

 Relative risks used instead of absolute which would take into account incidence rates

 After randomization the women were free to decide whether to continue their assigned treatment or whether to undergo diagnostic procedures

 The rate of unblinding in the E+P group was 45%, so almost ½ of women knew their treatment group

 High drop out rates - 43% of treated group and 38% of placebo group stopped their medication

 Average age of patient 10-15 yrs. above average age of menopause

 Media “took off” with results

WHI Data - Where are we now? Fun Hawaii Facts

 Residents of Hawaii live longer than in any other state, average life expectancy of 81.5 years, about three years longer than the country’s average of 78.8 years

 Hawaii’s official state fish is the trigger fish called humuhumunukunukuāpuaʻa” (also one of the longest words in the Hawaiian language and the name is thought to be longer than the fish!) Called the Humuhumu,” for short, and is a “fish that grunts like a pig,” and named for the sounds it makes when cornered or caught.

WHI Extension Study

 2005-2010, 2010-2015

 Annual updates on health outcomes are collected by mail, with signed release to obtain medical records if needed Heart Disease

 Absolute risks seen in WHI low: 19 additional events per year per 10,000 women with HRT versus placebo

 Analysis of WHI showed excess risks seen primarily in older women with combination HRT

 No increased risks with ERT and some suggestion of benefit in younger women, < 10 yrs. from menopause

 Increasing data that synthetic progestins may negate some of the beneficial effects of estrogen on lipids and endothelial function

 13 yr follow up from WHI showed net neutral effects on CHD in both HRT and ET groups Timing Hypothesis and Heart Disease

 Various CHD events -nonfatal MI, coronary death, angina, and coronary artery revascularization were significantly reduced by 34% to 45% in the ET group relative to placebo in women aged 50 to 59, but not women aged 60 to 69 or 70 to 79

 Number of studies since WHI including coronary angiography study, calcification study, and meta-analysis showed <10 yrs. since menopause or age 50-59 did not have increased CHD risks and suggestion of benefit

 Large prospective RCT Danish Osteoporosis Prevention Study (2012) showed 52% reduction death, MI, heart failure in HRT users, average age 50, over 10 year period (also found no increased breast ca or stroke risks)

 No major organization has said to use hormones for primary prevention

Heart Disease

 “ Timing Hypothesis” most studies now suggest timing since menopause affects risk of CHD

 Types of estrogen may effect risks of CHD, transdermals have more favorable effects on markers for CHD

 No data that suggests that MHT should be used for secondary prevention in women with CHD Stroke

 In a meta-analysis of randomized trials (including HERS, WEST, and WHI), both ERT and HRT associated with an increase in ischemic stroke, but not hemorrhagic stroke

 Increases in all age groups but in younger women 50-59 no absolute increased risks

 Studies have shown a trend toward more fatal strokes in women on oral ERT

 Studies have shown low dose transdermal not thought to increase risk of stroke

VTE Risks

 Meta-analysis have showed that oral MHT use causes about 2 fold increased risk of DVT/PE

 Studies suggest older age and obesity affects risks

 Data from WHI show risks not changed by smoking, ASA use or

 3-7 fold higher if Factor V Leiden VTE Risks- Type and Dose of MHT

 Type of estrogen may matter: small studies have shown that conjugated , but not esterified (-derived) estrogens, increase risk

 Meta-analysis showed that transdermal routes not associated with increased VTE risks – oral, but not transdermal elevate CRP levels which is a marker for CHD risks

 low-dose MHT, (0.3 mg conjugated estrogen) has less effects on coagulation and inflammatory markers than standard dose therapy and lower VTE risks

 Type of progestin may matter- large Million Women Study showed higher risks with MPA

Mortality

 When WHI reanalyzed by age, a significant 30 percent mortality reduction was seen in women under 60 years of age using MHT

 Absolute reductions: 5.3 and 5 fewer deaths per 1000 per five years of combined estrogen-progestin or unopposed estrogen use, respectively

 meta-analysis showed overall mortality not reduced with MHT in women over age 60

 Meta-analysis of 19 RCT of MHT for women under 60 showed 27 percent reduced mortality with HT when compared with placebo , absolute risks: 1 in every 119 women treated with HT did not die at five years compared with untreated patients Breast Cancer

 Risk of breast ca in HRT users seen in year 3 for prior users and year 4 for first time users, absolute risk 8 excess cases per 10,000 person-years. Persistent increased risks in 13 yr fu in HRT group but decreased over time

 Epidemiologic studies have shown risks of breast cancer drop off when HRT discontinued

 Trend toward lower risk of breast ca in ERT arm, HR .79, and that has persisted with long-term follow up (13 years)

Breast Cancer

 Not clear if starting hormones closer to menopause is associated with greater risks

 Length of ERT and risk? In Nurses Health Study long-term ERT associated with risk of breast ca (>15 yrs.) but not short term

 Studies have shown than breast cancer risk is not furthered increased in women with a family history- mainly independent risk factors

Why would ERT alone be associated with decreased risk of breast cancer?

 One hypothesis is that in menopausal women with low endogenous estrogen maybe exogenous estrogens induce apoptosis in existing tumors

 What about ovarian status - women using ERT alone have had a hysterectomy with possible oophorectomy, which decreases risk of hormone positive breast cancer

MHT and Breast Cancer Prognosis

 Impact of HT on breast cancer prognosis and mortality unclear

 2010 follow-up analysis of WHI showed similar grade and histology but more node positive disease, more deaths in HRT. But overall numbers small

 Epidemiologic studies have suggested that breast cancer in women taking MHT (ERT and HRT) has a relatively good prognosis and improved survival when compared with breast cancer that develops in women not taking MHT Progestins and Breast Cancer

 One theory is that progestins may cause an increase in cell division in mammary tissue leading to an accumulation of DNA errors

 Type of progestin may increase risk – large prospective cohort showed MPA increased risk but not natural progestin

Bones

 WHI showed that both HRT and ERT users had 1/3 lower risks of both vertebral and hip fractures

 For women ages 50 to 59 years, the estimates of benefit were 4.9 and 5.9 fewer fractures per 1000 women per five years of HRT or ERT use, respectively

 Progestins have not found to change benefits on bones

 Studies have shown benefits with current users and long-term users, possibly dose dependent fashion, although trials showing benefits even with ultra low dose estrogens Bones

 No data that when women stop their HRT or ERT that they lose BMD at a faster rate. At 13 yr fu in WHI persistent reduction in fractures for HT arm

 Studies in general show estrogen as effective as bisphosphonates in preventing bone loss

 Estrogen therapy is FDA approved for prevention of osteoporosis, but not treatment

 Because of the risks found in the WHI, MHT not recommended for first line therapy for protection from bones

MHT and Cognitive Function

 WHI Memory Study (WHIMS), an ancillary study of the WHI, showed no global cognitive benefits of HRT/ERT in older, non-demented postmenopausal women and led to accelerated cognitive decline

 Some epidemiologic studies suggest that women who start HT soon after menopause have a decreased risk of later , while women who start many years after menopause do not

 Recent report from Kronos Early Estrogen Prevention Study (KEEPS) examined the effects of up to 4 y of MHT on cognition and mood in recently postmenopausal women and found MHT did not affect cognition (June 15 PlosMed)

 Several small, RCT’s have evaluated estrogen treatment of women with Alzheimer disease: studies all small but no difference in tests of cognition in women on MHT vs placebo Endometrial Effects of MHT

 Well established that unopposed ERT increases risk of endometrial hyperplasia and progestins are protective

 Equivalent doses of transdermal and oral estrogen appear to have similar effects on the endometrium

 Some reports that cyclic HRT (q3 or 4 mos.) has higher risk of endometrial hyperplasia then continuous

 Levonorgestrel- releasing intrauterine systems (LNG-IUS) - off-label use for endometrial protection and provides very high intrauterine but low systemic concentrations of levonorgestrel - almost all women develop a nonproliferative, atrophic endometrium, as good or better in protecting against endometrial hyperplasia

Results in Newly Menopausal Women

 Data limited as most studies draw from WHI which had fewer women in this subgroup

 Fewer CHD in ERT alone

 Lower mortality in both HRT and ERT

 Less Type 2 DM in both groups

 Less breast cancer in ERT group

 Less colorectal ca in HRT group

 Slight increased CHD and breast cancer in HRT but not considered significant because low incidence rates MHT- so where are we now?

 Current guidelines - use MHT for control of menopausal symptoms, not for prevention of disease

 Limit use of MHT to 5 yrs.

 Use lowest dose possible

 Consider transdermal estrogen as risks may be less (VTE and stroke)

 Consider micronized progestin as opposed to MPA as risks may be less (VTE and breast cancer)

 Continuous better for endometrial protection but greater risks to the breast

 Try to find lowest dose of progestin that protects the uterus but doesn’t harm the breast, consider cyclic therapy

MHT in newly menopausal women- Should we change recommendations?

 Increasing data supporting timing hypothesis for many outcomes

 Should we be using MHT in newly menopausal women to prevent cardiac disease and decrease overall mortality?

 Will MHT in this group prevent cognitive decline?

 What are the risks of NOT using MHT in this group? Hawaii Fun Facts

 Beaches are publicly owned lands in the State of Hawaii - meaning the public has full right of access to all beaches and shorelines throughout the Islands

 The Big Island is comprised of 4,028 square miles (10,432 km) and makes up 63% of State of Hawai’i’s total landmass

 Big Island is youngest of the islands, estimated to be 800,000 years old

What about the use of Bio-identical Hormones?

 Review of multiple data bases, identified only 3 RCT looking at bio-identical cream for hot flashes. 1 found that compounded cream was more effective than placebo, other 2 found that manufactured cream was not.

 Vaginal bleeding and were the most commonly reported adverse effects

– Whelan AM, et al. Bioidentical progesterone cream for menopause-related vasomotor symptoms: is it effective? Ann Pharmacother. 2013 Jan;47(1):112-6. Committee Statements on Bio-identical Hormones

 Evidence lacking to support superiority claims of compounded bioidentical hormones over conventional menopausal hormone therapy

 Efficacy and safety data lacking because of variability in purity  – American College of Obstetricians and Gynecologists Committee on Gynecologic Practice; American Society for Reproductive Medicine Practice Committee. Compounded bioidentical menopausal hormone therapy. Fertil Steril. 2012 Aug;98(2):308-12.

SERM with – “TSEC” Treatment of Menopausal Symptoms

 Selective Estrogen Menopause And Response to Therapy 3 (SMART-3) trial

 Goal is to provide symptom relief with estrogen and combine with a SERM to eliminate need for progestins to protect the uterus – or providing a tissue selective estrogen complex (TSEC)

 Found improvement of vaginal atrophy and menopausal symptoms

20 mg/conjugated estrogens .45 (Duavee) got FDA approval in 2013 for moderate to severe VMS and prevention of osteoporosis Alternatives to Hormones for Management of Menopause

Hot Flashes – Alternatives to Hormones

• Low dose – Venlaflaxine, , , , • Antihypertensive Clonidine • Gabapentin (Neurontin) • • Soy supplements • Herbal Products: best studied Black Cohosh • (in ) • Chinese • Alternative Therapies (Effexor) and Hot Flashes

 Most well studied – RCT’s, largest populations and longest trials

 Felt to improve overall well being

 Beneficial effects in days compared to

 Side effects - Dry Mouth, Decreased Appetite, , Sleeplessness

Venlafaxine (Effexor) and Hot Flashes

 Doses different than depression  depression 37.5 - 75 mg BID/TID - max 375 mg/d  hot flashes 37.5-75 mg/d - Most effective dose 75 mg/d

 Less sexual dysfunction at these doses

 May cause vaginal dryness given anticholinergic side effects Paroxetine and Hot Flashes

 Number of RCT’s have showed significant relief of HF’s compared to placebo, initially found success with both 10, 20 mg/day

 Lower dose, 7.5 mg (Brisdelle) FDA approved in 2013 for treatment of vasomotor symptoms (VMS)

Antihypertensive Clonidine (Catapres) and Hot Flashes

 Clonidine .1 mg/d PO or patch – 2 RCT have shown slight benefit in reducing number of hot flashes, some improvement in QOL

 Side effects - sleep difficulties, dry mouth, , and nausea

 Avoid with low blood pressure

Rymer J, et al (2000) BMJ, 321(7275): 1516–1519

Pandya KJ, et al. (2000) Annals of Internal Medicine, 132(10): 788– 793. Gabapentin (Neurontin) and Hot Flashes

 Gabapentin thought to decrease hot flashes by regulating calcium flow in and out of cells which is one mechanism for regulating body temperature

 A number of RCT’s and meta-analysis have shown improvement of HF’s with low doses of Gabapentin. Most effective dose felt to be 900 mg

 RCT compared gabapentin to conjugated estrogen(.625mg) and found gabapentin was as effective as estrogen in the treatment of postmenopausal hot flashes

• Reddy et al., Obstet Gynecol 2006

Gabapentin (Neurontin) and Hot Flashes

 Side effects like dizziness common and may cause sedation

 12 wk RCT, 59 women given gabapentin 300 mg TID vs placebo, found significant improvement in sleep quality in women on gabapentin • Michael E. Yurcheshen, J of Women’s Health, Sept 2009

is a newer compound that works similarly to Gabapentin. RCT’s have also shown this to be an effective treatment for hot flashes. Vitamin E and Hot Flashes

 Vitamin E 800 IU/day : marginal improvement compared to placebo in Randomized Controlled Trial (1 /day) No toxicity (1998)

 Overall not great data that it helps

 Meta-analysis raised concerns about megadoses of Vitamin E and increased mortality risk – most patients studied “not healthy”

What about Soy and Hot Flashes? Soy

– plant-derived compounds that bind to estrogen receptors (ER)

 Some bind weakly to ER-

 Many bind strongly to ER-

– Three main classes

( and daidzein): , soy products, lentils, chickpeas, red clover

( and ): wide variety of fruits, vegetables, and cereals; concentrated in flaxseed

(): bean sprouts, fodder crops (alfalfa) Scheiber MD, Rebar RW. Menopause. 1999;6:233-41.

Is Soy Beneficial in Reducing Hot Flashes?

 Systematic review and meta-analysis of RCT’s in Pubmed and Cochrane Clinical Trials Register Database (to Dec 2010) evaluating the effects of extracted or synthesized isoflavones from 6 wks.- 12 mos. on the frequency and severity of hot flashes found significant reductions in frequency and severity - Supplements with more than 18.8 mg of genistein (the median for all studies) were more than twice as potent at reducing hot flash frequency than lower genistein supplements

• Taku K, et al. Menopause. 2012 Mar 19 Is Soy Beneficial in Reducing Hot Flashes?

 Review of RCT’s of isoflavones and amino acid preparation effects on hot flashes and at least one other menopausal symptom between 2004 and July 2011

– five trials of soy preparations, two (6g soy germ extract and 25 g in soy nuts) significantly decreased hot flashes, but no other symptoms. – seven trials of other isoflavones, six significantly reduced hot flashes – One trial of red clover (80 mg) significantly reduced mood symptoms – One trial of Rexflavone (350 mg) significantly reduced sleep symptoms – One trial of red clover (80 mg) reduced cognitive symptoms – In one trial, red clover isoflavone (80 mg/day) significantly relieved hot flashes, mood, pain, and cognitive symptoms. – Amino acids yielded no significant results

– Thomas AJ, . Maturitas. 2014 Aug;78(4):263-76.

Cimicifuga Racemosa (Black Cohosh) and Hot Flashes

 Older studies generally showed a benefit but relatively poor quality studies

 Review in of RCT’s looking at multiple herbal therapies showed no improvement in hot flashes with Cimicifuga racemosa compared to placebo but improvement when combined with perforatum (St. John’s wort) – Laakmann E, et al. Gynecol Endocrinol. 2012 Mar 2.

 Review of 16 RCT using a median dose of 40 mg per day of Black Cohosh, mean duration of 23 weeks found no significant difference between black cohosh and placebo in frequency of hot flashes – Cochrane Database Syst Rev. 2012 Sep 12;9 Other Alternatives for Hot Flashes

 Acupuncture - a review in 2009 found 5 of 6 trials showed no benefit of acupuncture compared to sham or placebo.

• Menopause. 2009;16(5):1065–1073.

 Small RCT from showed yoga improved total menopausal rating score (2011) but review of literature (2009) did not find a benefit for reducing hot flashes

• Joshi S, et al. Menopause Int. 2011 Sep • Lee MS, et al. Menopause. 2009

Treatment of Hot Flashes - Lifestyle Modifications

 Regular exercise, particularly improves sleep

 Avoid foods or climate changes that trigger hot flashes – , , spicy foods

 Stress reduction – yoga, meditation, hypnosis, therapy, massage, “pleasure activities” Hawaii Fun Facts

 Population of the Big Island – approximately 185,000

 Called the 2 sided island- Hilo on the east is wet and tropical with > 150 inches of rain annually and the Kona side gets < 10 inches of rain annually

 Mauna Kea observatory houses the worlds largest telescope

What About other Quality of Life Issues?

• Vaginal Dryness

• Decreased Libido Vaginal Dryness and Resultant Dyspareunia

 More common since women stopping MHT with publication of WHI

 Begins within 6 months of estrogen loss

 Treatments include local or systemic estrogen

 Tablets, ring, creams – Vagifem-10mcg nightly x 2 weeks then 3x/wk – Estring-2 mg q 3 months – Estrace(0.01%-2 gms nightly x 2 weeks then 3x/wk) – Premarin (0.625 CE/gm-1gm nightly x 2 weeks then 3x/wk)

 Estrogen cream for introitus

Local vs. Systemic Estrogen

 Local estrogen therapy is generally preferred for Vaginal Dryness/Dyspareunia

– Targeted efficacy to vaginal tissues – Minimal systemic absorption, fewer adverse effects – Progestin component is not needed in women with uterus

 Local estrogen thought to improve lubrication, increase blood flow and sensation in vaginal tissues NAMS. Menopause. 2010;17:242-255. NAMS. Menopause. 2007;14(3):357-369. Other Treatments for Vaginal Dryness

 Pilocarpine – stimulates muscarinic cholinergic receptors  Phase 3 trial did not show this to be effective

 Loprinzi et al, J Support Oncol. 2011 May-Jun

 Lots of OTC products for reducing dryness, improving moisture, improving libido – typically make it to the market with little or no data

Ospermifene - SERM for Vaginal Dryness

• FDA approved Feb 2013

• Trade name Osphena

• Approval for moderate to severe dyspareunia and vulvar and vaginal atrophy

• Approval based 3 RCT of 1889 pts., first 2 looked at effectiveness and 3rd safety

• Recommended dose is one 60 mg tablet with food Ospermifene

• Reported adverse effects - hot flashes, vaginal discharge, muscle spasms, and excessive sweating

• Serious risks • thrombotic and hemorrhagic strokes: 0.72 and 1.45 per 1000 women, respectively • deep vein thrombosis: 1.45 per 1000 women

 Contraindicated in breast cancer patients

Local DHEA for Vaginal Dryness

 Randomized, double-blind and placebo-controlled phase 3 trial of (DHEA) applied locally in the vagina for treatment of vaginal atrophy in 216 postmenopausal women.

 Found three doses (0.25%, 0.5%, and 1.0%) of DHEA ovules applied intra-vaginally daily induced significant beneficial change in the percentage of vaginal parabasal and superficial cells and pH as well as in the most bothersome symptoms at 2 weeks. Continued improvements noted at 12 wks.

• Menopause. 2009 Sep-Oct;16(5):907-22. Menopause and Sexual Functioning

 Many women note decreases in libido or desire

• If experiencing sleep disturbances, may influence sexual desire

• Other life stressors may affect sexual functioning – job, stressors related to children or aging parents, relationship satisfaction

• Body image changes may influence desire for both partners – gray hair, wrinkles, sagging body parts

• Surgical procedures may affect sexual functioning – hysterectomy, breast cancer surgery

Menopause and Sexual Functioning

 Associated medical conditions may affect sexual functioning – heart disease, cancer, arthritis, urinary incontinence

 Certain medications may affect desire and sometimes ability to have orgasm – blood pressure medicines, antidepressants

 Prior sexual attitudes and degrees of satisfaction may influence interest and activity during and after menopause

 Vaginal dryness and irritation may affect sexual functioning Treatment of Decreased Desire

• Lifestyle changes – regular exercise, decreasing stress, “be happier”, pelvic muscle strengthening, improving relationship/emotional intimacy

• Treat underlying conditions – medical and side effects of medicines

• Hormone therapy - few studies evaluating success of this

 Topical estrogen

 Systemic estrogen

 Estrogen ± progestin

 Estrogen/androgen

 Androgens

• Herbal products that thought to cause smooth muscle relaxation and improved genital blood flow – lack of data

Testosterone for Decreased Libido

 Non FDA approved

 Can be compounded in many forms – oral, sublingual, topical creams

Patch – number of trials have shown benefit in improving female sexual functioning

 N Engl J Med 2006; 354:1497-1506  N Engl J Med. 2008 Nov 6;359(19):2005-17  Menopause. 2006 May-Jun;13(3):387-96

 Cochrane review in 2005 showed that HT with testosterone improved libido and sexual functioning more than HT alone Herbal Remedies for Decreased Libido - DHEA

 RCT looking at whether restoring circulating DHEA levels in PMP women to the levels seen in young individuals improves sexual functioning:  93 PMP women not on ERT enrolled in 52-week trial, received DHEA 50 mg or placebo  Outcome measures were the change in total satisfying sexual events (SSE), the change in the Sabbatsberg Sexual Self-Rating Scale (SSS) score, the Psychological General Well-Being Questionnaire (PGWB), and the Menopause-Specific Quality of Life Questionnaire (MENQOL)

 Results: at 26 wks., no significant differences between the groups in any outcome measures. More women in the DHEA group experienced acne and increased hair growth. J Sex Med. 2009 Sep;6(9):2579-90. Epub 2009 Jul 10

Bupropion (Wellbutrin) for Decreased Libido

• Frequently used to counterbalance sexual dysfunction associated with SSRI antidepressants

• Pilot studies showed a potential benefit, small 6 week RCT of 41 patients showed no benefit with SR in any measure of sexual functioning

• J Clin Psychiatry. 2005 Jul;66(7):844-8. • 8-week trial of bupropion 150 mg/d in 20 women with breast ca prior chemotherapy and were currently on hormonal therapy • Evaluated with Arizona Sexual Experience Scale (ASEX) at baseline, 4 and 8 wks • Results showed improvement in sexual functioning at 4 and 8 weeks.

• Ann Oncol. 2006 Dec;17(12):1792-6. Epub 2006 Sep 15. What about Viagra in Women?

Viagra for Decreased Libido

 Preliminary trials have suggested benefit for sexual arousal disorders

 Industry sponsored trial: 98 women with normal sexual function before treatment for depression, successfully treated with SRI’s for a mean of 28 mos, substantial sexual dysfunction associated with use

 Randomized to sildenafil (50–100 mg) or placebo - drugs were taken 1 to 2 hrs. before anticipated sexual activity

– Results - baseline to 8 weeks, sildenafil-treated women reported a mean improvement of 1.9 points on a global sexual function scale (range, 1–7 points) compared with 1.1 points for those who received placebo - statistically and clinically significant

– Treatment resulted in significant improvement in ability to achieve orgasm as measured on three additional scales

– Improvements in several measures of satisfaction and enjoyment

Nurnberg et al. JAMA 2008 Addyi (flibanserin) for Hypoactive sexual desire disorder

 Not the “New Viagra”

 Novel, non-hormonal, multifunctional antagonist (MSAA) that acts in the CNS

 Acts to increase dopamine and norepinephrine (both responsible for sexual excitement) while decreasing serotonin (responsible for sexual satiety/inhibition)

Addyi (flibanserin) for Hypoactive sexual desire disorder

 24-week Phase 3, placebo-controlled studies in premenopausal showed flibanserin resulted in a significant increase in sexual desire, decrease in distress from the loss of sexual desire and an increase in the frequency of satisfying sex

 most common side effects were dizziness, nausea and sleepiness

 On June 4, 2015, an FDA Advisory Committee recommended approval of Addyi for HSDD Treatment of Sexual Dysfunction -

 Set goals, team approach

 Education

 Open communication important for both partners

 Alter sexual behavior as needed to accommodate for physical, emotional and social changes

 Therapists that specialize in sex therapy

CASE STUDY

50 yr. old G2P2 perimenopausal woman presents with complaints of significant night sweats interfering with her ability to sleep. She has mild hot flashes during the day. She has never had a bone mineral density but her mother has had a hip fracture due to osteoporosis. Her 46 yr. old sister was diagnosed with breast cancer at age 43, treated with lumpectomy and radiation and currently is doing well. There is no other family history of cancer. Questions

 1. Would you offer her MHT?

 2. If yes, how long would you continue it?

 3. If no, what would you offer for alternative treatments?

 4. Would your treatment differ if you knew she had underlying heart disease?

Conclusions and Thanks

 Hopefully you will now know something more about menopause and hormones, alternatives to hormones, management of vaginal dryness and sexual functioning

 And if not, that you know more about the Big Island of Hawaii!