OVERVIEW OF MENOPAUSE

Transcription

1 OVERVIEW OF MENOPAUSE Nicole Budrys, MD, MPH Reproductive Endocrinology Michigan Center for Fertility and Women s Health Presented at SEMCME March 13,2019

2 Objectives Define menopause Etiology of menopause Timing of menopause and relationship with symptoms Review menopausal symptoms and health risks Hormonal therapies Nonhormonal therapies

3 Disclosures None

4 How do we define menopause A. No period for 12 months B. Elevated FSH levels in the menopausal range C. When childbearing no longer possible D. The permanent stop of periods due to egg depletion

5 Menopause Basics Time at which menses cease due to depletion of oocytes in the ovary Retrospective diagnosis 12 months of amenorrhea Reproductive Senescence Average age of onset 51.3 years of age Affects health and quality of life

6 Which is true regarding egg numbers and age? A. The greatest number of eggs a woman will have is at birth B. The number of eggs at birth is about 6 million C. The number of eggs at the time of menarche is 300,000 to 500,000 D. At menopause there are no eggs left in the ovaries

7 Oocyte Counts and Age

8 The Reality of Oocyte Number and Menopause

9 Pathological Exploration of Oocyte Number

10 Oocytes and Age

11 Menopausal Threshold

12 Why are FSH levels high in menopause? A. Estradiol is low due to decreased egg numbers B. Inhibin is low due to decreased egg numbers C. AMH is low due to decreased egg numbers D. No idea. I am not an endocrinologist.

13 HPO axis feedback FSH E2

14 HPO axis feedback FSH E2 E2 INHIBIN INHIBIN

15 Why are FSH levels high in menopause? A. Estradiol is low due to decreased egg numbers B. Inhibin is low due to decreased egg numbers C. AMH is low due to decreased egg numbers D. No idea. I am not an endocrinologist.

16 Which of the following is true regarding the menopausal transition? A. All women have similar changes in menstrual patterns in the perimenopause. B. Hot flashes occur after menopause. C. The transition into menopause can take up to 3 years D. Symptoms of hypoestrogenism occur after menopause

17 STRAW Workshop Menopause 19(4)

18 What you are worried about: Long Term Health Risks of Hypoestrogenism Increased risk of cardiovascular disease Decreased bone density/ risk of fracture- Dr Rao

19 Is estrogen the fountain of youth?

20 The Back Story on Estrogen Therapy- How did we get here? CV risk lower than males before menopause but higher after Multiple small studies showed patients taking HT had decreased risk CV? Should we give to prevent heart disease? WHI provided large scale testing of hypothesis Two groups of postmenopausal women average age 61 Prior hysterectomy: conjugated estrogen (CEE) Intact uterus: CEE plus progestin- prempro Primary outcome: coronary artery disease

21 WHI Extended Post-stop Phase Coronary Heart Disease CEE + MPA Neutral Intervention 1.09 [ ] 1.18 [ ] Per Year Risk 2/10,000 Per Year Risk 6/10,000 CEE-alone Neutral 0.92 [ ] 0.94 [ ] Per Year Risk 4/10,000 Per Year Risk 3/10,000 RCS Mason et al., JAMA 2013;310: Estrogen alone or combined with Progestin does not harm or protect against CHD This is NOT what most people {providers & patients} think WHI study shows

22 5) Why was WHI stopped early? A. Increased risk of venous thromboembolism B. Increased stroke risk C. Increased risk of breast cancer D. Increased CV events

23 WHI Extended Post-stop Phase Breast Cancer Increased Risk CEE + MPA risk persisted Intervention HR 1.28 [ ] {HR 1.24 [ ] on HT} Per Year risk 10/10,000 Per Year risk 9/10,000 Time-dependent analysis suggests a year-by-year of HT reduction (data not shown) Mason et al., JAMA 2013;310: RCS: CEE + MPA study was stopped for breast ca risk HT is an accelerant & not a cause. Dx was advanced More advanced-stage disease may reflect breast density from HT GOOD NEWS: We should be stressing that 9,990/10,000 women had years of exceptional health (on HT). [Lila Nachtigall, First to Know, Oct 3, 2013]

24 WHI Extended Post-stop Phase CEE-alone Reduced risk became statistically NON-significant HR 0.79 ( ) HR 0.79 ( ) Per Year Risk -7/10,000 Per Year Risk -7/10,000 Mason et al., JAMA 2013;310: RCS Bad actor in this breast/hormone story remains a mystery Progestin is an often accused, but unproven, suspect Role of other estrogens and other doses unknown

25 WHI [CEE] Extended Post-stop Phase Stroke CEE + MPA Neutral Intervention 1.16 [ ] 1.37 [ ] Per Year Risk 5/10,000 Per Year Risk 9/10,000 CEE-alone Neutral RCS 1.15 [ ] 1.35 [ ] Per Year Risk 5/10,000 Per Year Risk 11/10,000 Mason et al., JAMA 2013;310: Estrogen alone study stopped for possible stroke risk Estrogen alone or combined with Progestin does not harm or protect against CVD This is NOT what most people think WHI study shows

26 THE TIMING HYPOTHESIS aka Critical Window Hypothesis

27 What your patient is worried about: Other Menopausal Symptoms Hot flashes Vulvovaginal/Urogenital Sexual Depression Difficulty sleeping Cognitive dysfunction Weight gain

28 Vasomotor Symptoms

29 SWAN Study: Reported Prevalence of Vasomotor Symptoms Ages 40 to 55 Years % of Women Reporting Hot Flushes/Night Sweats n = 12,357; SWAN = Study of Women s Health Across the Nation. Gold EB, et al. Am J Epidemiol. 2000;152: Race/Ethnicity Race/Ethnicity n African-American 3650 Hispanic 1712 Caucasian 5746 Chinese 542 Japanese Duration of VMS

30 Estrogen Therapy Reduces Vasomotor Symptoms Results of a 6-month, double-blind, placebo-controlled, crossover study of the effects of oral CEE (1.25 mg/d) on hot flushes Average Number of Hot Flushes Per Week Mean Age, 52 Years Placebo CEE Crossover Placebo CEE Months CEE Placebo n = 30. A significant (P <.05) reduction in number of hot flushes was reported for women taking estrogen compared with placebo. Coope J, et al. BMJ. 1975;4:

31 Acceptability of Estrogen Use Choose the statement which best reflects your/your program s approach to prescribing estrogen to postmenopausal women. A. My preceptors do not prescribe estrogen for postmenopausal symptoms. If a patient wants estrogen or has been on it before, we send them to someone who prescribes it. B. A few preceptors prescribe estrogen, but most do not. C. We use estrogen regularly for postmenopausal patients. D. We have so few postmenopausal patients that I don t know.

32 Treatment for hot flashes Lifestyle changes Hormonal therapies Non hormonal therapies

33 Lifestyle Changes Dress in layers Keep temperature low especially in bedroom Avoid spicy foods, caffeine, alcohol Exercise regularly Maintain a healthy weight

34 Hormonal Therapies Estrogen-which one and how much? Oral Transdermal Bioidentical Vaginal Progestins vs Natural progesterone DHEA/Intrarosa/prasterone Vaginal atrophy dysparunia

35 Which is not a contraindication to estrogen therapy? A. Current or history of estrogen sensitive cancer B. Diabetes C. Current of history of VTE D. Active liver disease

36 Contraindications to Estrogen Therapy

37 Copyrights apply

38 Can she just take estrogen? All women with an intact uterus will need progestin therapy to help prevent the effects of unopposed estrogen. Provera 10mg x 10d each month Choose a combination pill: prempro Micronized progesterone: may have fewer risks for breast cancer Levonorgestrel IUD

39 Length of Treatment ACOG Lowest dose for shortest time But what if your patient still has symptoms

40 Vulvovaginal Atrophy Hypoestrogenism causes thinning and atrophy of the vaginal tissues. Itching Dysparunia Urinary symptoms as the urogenital/periurethral tissues thin Vaginal estrogen applied topically 1-2 x/day May take 1-2 months to see full effects Estrace cream widely available but may be costly Not systemically absorbed

41 8) Do women using vaginal estrogen need progesterone to protect their uterus? A. Yes B. No

42 Nonhormonal Therapies What is bothering her most?

43 SSRI/SNRI Mild to moderate relief of hot flashes 7 pooled studies Venlafaxine 37.5mg daily x 1 week then 75mg daily to reduce nausea Desvenlafaxine: no ramp up needed Paroxetine 7.5 mg Do not use in women on Tamoxifen as blocks metabolism to active metabolite of Tamoxifen Citalopram 20mg Not effective: Sertraline and Fluoxetine

44 Neurontin Extended release mg per day 900 mg most effective 30-50% reduction in hot flash symptom scores Improves sleep Predominantly nighttime symptoms

45 Oxybutynin Extended release 5mg daily 90% of patients refractory hot flashes prior to start 70% reported partial or complete relief 12% stopped due to side effects

46 Glycopyrrolate/Robinul Systemic anticholinergic 1mg daily Increase weekly by one tablet per day until symptoms reached to 10 mg/d May cause dry mouth, dry eyes, urinary retention

47 Alternative Therapies The trouble with studies on menopause symptoms. Effective at 3 months, but no different than placebo at 6 months Soy Red clover Dong Quai Kava Evening primrose oil Yes to accupuncture

48 Estrogen Gold standard for treatment of symptomatic menopause Reduces bone loss Not proven to reduce risk of cardiovascular disease Should be initiated in early menopause Smallest dose for shortest period of time

49 Conclusions Lots of options for patients Ask about associated symptoms not just hot flashes Choose a treatment that will help most prominent symptoms Give patient realistic expectations

50 Questions? Nicole Budrys