1. Menopause 2010 Katherine Beach, CNM Maine Medical Partners Women’s Health

2. Definition of Menopause Cessation of Menses for 12 consecutive months –Genetic factors –Lifestyle factors (smoking, alcohol abuse) –Long term health –Transition time is very individual Ranges from easy to very difficult

3. Age of Menopause Average age in the US is 51 –Range is 42-58 years Average of 2 years earlier in smokers Diagnosis is given retrospectively Earliest clinical finding is a decrease in cycle length –Age 18-30: 30 day cycles –Age 40: 25 day cycles –Age 45: 23 day cycles

4. Outline/Introduction Menopause as time of transition Health considerations –Cardiac disease –Loss of bone mass –Breast cancer Current understanding of hormone therapy

5. General Considerations Life expectancy is now 80 years –30 years longer than in 1910 One-third to One-half of life is post- menopause Public Health Impact –Cardiac disease –Osteoporosis

6. 10 Leading Causes of Death Heart Disease Cancer (Lung Ca in Maine) Stroke Chronic Respiratory Disease Accidents/Unintentional Injuries Diabetes Alzheimer’s Disease Influenza/Pneumonia Nephritis/Kidney Disease Septicemia

7. Peri-Menopause Defined as the years surrounding the final menstrual period Often characterized by hot flashes/night sweats Can be accompanied by mood swings, irritability

8. Counseling the Perimenopausal Woman Discuss changes in cycles Expectations Seek medical attention if: –Bleeding more frequently than every 21 days –Bleeding is heavy for more than 7 days –Hot flashes and/or insomnia are disturbing to daily life

9. Terminology Natural/spontaneous menopause –The final period, confirmed after 12 consecutive months of amenorrhea with no obvious pathologic cause Induced menopause –Permanent cessation of menstruation after bilateral oophorectomy or iatrogenic ablation of ovarian function

10. Terminology (continued) Premature menopause –Menopause reached at or under age 40, whether natural or induced Premature ovarian failure –Ovarian insufficiency experienced under age 40, leading to permanent or transient amenorrhea

11. Perimenopausal Endocrine Changes Hypothalamic-ovarian axis –Inhibin levels decrease –Ovaries become resistant to pituitary FSH –This results in higher estradiol levels –Corpus luteum function decreases, leading to shorter luteal phases and lower progesterone levels –End result is shorter cycles with heavier bleeding

12. Initial Clinical Symptoms Hot flashes (75% of women in the US) –Sleep disturbances –Insomnia Vaginal dryness Irritability Mood swings

13. Multi-Organ Changes Due to Estrogen Loss Urinary and reproductive tracts Bone Vascular lining Skin Brain Central nervous system Teeth

14. Later Clinical Symptoms Osteopenia/Osteoporosis –Higher incidence if Caucasian or Asian descent –Slender body build –Positive family history –Early estrogen deficiency –Abuser of tobacco and/or alcohol –Low calcium and Vitamin D intake –Sedentary lifestyle Cardiac disease

15. Screening for Bone Density Loss Dual Energy X-Ray Absorptiometry (DEXA) is current standard of care Non-invasive Accurate Bone Density is measured in standard deviations from the norm

16. Diagnosis of Osteoporosis Using WHO Criteria NormalT-score above –1 OsteopeniaT-score between –1 and –2.5 OsteoporosisT-score of –2.5 or below

17. When to start screening and how often should it be done? Usually best to obtain baseline at time of menopause If normal, repeat in 5 years If abnormal, recommend treatment and repeat in 2 years –For all women, Calcium 1500 mg/day and Vitamin D 1000 IU/day –Daily weight-bearing exercise Osteopenia vs Osteoporosis

18. Estrogens Produced by the Body Estradiol –Major estrogen secreted by the ovaries Estriol –Weak peripheral metabolite of estradiol and estrone Estrone –Minor estrogen secreted by the ovary and produced from peripheral conversion of androstenedione

19. Who Should Use Hormone Therapy? Current thinking is to use HT to relieve hot flashes on a short-term basis (2-5 years) and at the lowest dose that will achieve the desired effect Should be initiated at the time of menopause, not many years after menopause

20. Women’s Health Initiative First Randomized Control Trial for Women –Not until 2002 Primary objective was prevention of Cardiac Disease ET and EPT neither reduce nor increase incidence of cardiac disease Average age of women in study was 63 yrs Data may not translate to more typical woman seeking HT at age 50

21. WHI (continued) Also looked at Breast Cancer, Stroke, DVT, Dementia, Diabetes, Endometrial Cancer, Osteoporosis, and Depression with use of HT EPT arm of study was discontinued early ET arm continued On-going studies are continuing

22. Terminology ET—Estrogen Therapy EPT—Combined Estrogen-Progestogen Therapy HT—Hormone Therapy (includes both ET and EPT) Progestogen—Includes both natural progesterone and synthetic progestins

23. Local Estrogen Therapy for Vaginal Dryness Can be initiated safely at any time in a woman’s life 3 forms currently available –Estrogen cream (1 gram per vagina 1-2 times per week) –Vagifem tablets (1 tablet per vagina once a week) –Estring (1 ring per vagina every 3 months)

24. Vaginal Estrogen Treatment Local effect, not systemic –Does not increase risk of cardiac disease, stroke, breast cancer, or DVT –Relieves dyspareunia (painful intercourse) that is due to vaginal atrophy –Will not improve decreased libido –May benefit urge incontinence –May reduce risk of recurrent UTIs

25. Systemic Hormone Therapy Must use both estrogen and progesterone if uterus is intact to protect endometrium Estrogen alone will cause hyperplasia and can lead to uterine cancer Safe to use estrogen alone if uterus is absent At usual doses, does not affect weight or Body Mass Index

26. HT and Quality of Life Must weigh risks and benefits HT can improve health-related QOL through mood elevation and decreased menopause symptoms Less fatigue (as result of better sleep) often leads to fewer mood swings and less irritability

27. HT and Osteoporosis Not first line of therapy Should use bisphosphonates if possible –Fosamax –Actonel –Boniva If bisphosphonates are not tolerated (GI upset) can use HT, but patient must understand risks Osteoporosis is long-term problem—cannot be addressed with 2-5 year therapy in most cases

28. HT & Cardiac Disease HT may reduce cardiac disease risk if initiated in younger and more recently postmenopausal women Follow-up studies from WHI show longer HT duration may be associated with less mortality in women who initiate therapy at time of menopause and continue use beyond 5 years

29. HT & Cardiac Disease (continued) HT not recommended for women who have gone through menopause more than 5 years ago Even short-term use in this group of women is associated with increased risk of cardiac disease HT currently not recommended as sole or primary indication for coronary protection in women of any age

30. Stroke & Venous Thromboembolism Systemic HT increases risk of ischemic stroke and therefore HT is not recommended for primary or secondary prevention of stroke Oral HT increases risk of VTE in women over age 60 VTE risk emerges soon after HT initiation (1-2 years) and decreases over time Possible lower risk with transdermal patch than with oral HT, but no RCT evidence

31. HT & Diabetes Mellitus HT reduces new DM onset Inadequate evidence to recommend HT for sole or primary indication of DM prevention in peri- or postmenopausal women Transdermal ET may have advantages over oral route in women with DM

32. HT & Breast Cancer Breast cancer risk increases with HT use beyond 5 years Increased absolute risk of EPT in WHI was rare (4-6 cases/10,000 women/yr of EPT for >5 years) WHI ET trial showed no increased risk after 7.1 years (6 fewer cases/10,000 women/yr of ET use; not statistically significant)

33. HT & Breast Cancer (continued) EPT and, to a lesser extent, ET, increase breast cell proliferation, breast pain, and mammographic density EPT may impede diagnostic interpretation of mammograms HT not recommended if personal history of breast cancer Evidence unclear when family history of breast cancer exists (no RCTs)

34. HT & Mood/Depression Progestogens in EPT may worsen mood if woman has a history of premenstrual syndrome, premenstrual depressive disorder, or clinical depression Controversial if ET augments antidepressant effects of SSRIs (selective serotonin re-uptake inhibitors)

35. HT & Dementia HT not recommended at any age for the prevention of dementia HT seems to increase dementia if initiated at age 65 or older Inadequate data as to whether HT started soon after menopause increases or decreases later dementia risk Limited data do not support HT for prevention of Alzheimer’s disease

36. HT & Premature Menopause, Premature Ovarian Failure Most data suggest HT has protective cardiac effect in these women Data regarding HT in women experiencing menopause at the typical age cannot be extrapolated to these women Likely that risks attributable to HT are smaller and benefits greater in these younger women, but no RCTs exist

37. HT & Total Mortality HT may reduce total mortality when initiated soon after menopause Both ET and EPT may reduce total mortality by 30% when initiated in women <60 years old HT not associated with mortality reduction among women who initiate HT at >60 years old

38. HT Dosages Therapeutic goal is lowest effective estrogen dose (plus corresponding low progestogen dose for women with a uterus) consistent with individual treatment goals, benefits, and risks Lower doses better tolerated, may have more favorable benefit-risk ratio than standard doses

39. HT Dosages (continued) Estrogen –0.3 mg oral conjugated estrogens –0.5 mg oral micronized 17ß-estradiol –0.014-0.025 mg 17ß-estradiol patch Progestogen –1.5 mg oral medroxyprogesterone acetate –0.1 mg oral norethindrone acetate –0.5 mg oral drospirenone –50-100 mg oral micronized progesterone

40. HT Routes of Administration No clear benefit of oral vs. transdermal if no risk factors Transdermal bypasses the liver, and therefore is recommended for women with liver disease Transdermal ET may be associated with lower DVT risk than oral route Local ET preferred when solely vaginal symptoms Systemic progestogen required for endometrial protection from unopposed systemic ET

41. Bioidentical Hormone Therapy Custom-made HT compounded in accordance with healthcare provider’s prescription Custom BHT may provide doses, ingredients, and routes of administration not commercially available –Apothecary By Design Salivary hormone testing used to adjust custom BHT levels is not justified on any scientific basis

42. Evaluation Prior to HT Initiation Complete history and physical exam Mammography within the 12 months before HT initiation and yearly while on HT DEXA as needed After discussion of risks and benefits, begin therapy as close to menopause as possible Never begin therapy in women over age 60

43. Individualization of Therapy Imperative to review risk profile Each woman must be informed of her known risks Acceptance of HT risks varies with the individual Acceptance of HT risks varies as to primary indication (e.g. relief of hot flashes now vs. prevention of osteoporosis later in life)

44. Duration of Use Again, must individualize for each woman Review risk/benefit ratio each year Use lowest effective dose May continue for further osteoporosis prevention/treatment if alternate therapies are not acceptable Must have clinical supervision

45. When HT is Discontinued… 50% chance of symptoms recurring Hot flashes are similar whether tapered or abrupt discontinuance Data conflicting regarding breast cancer incidence after discontinuance Decision to resume HT must be individualized

46. Explaining Risk Essential to understand basic concepts of risk and be able to explain to patients Tailor the discussion to the individual patient Be sensitive to whether she wants numerical information, your honest opinion, or both Providing figures for absolute risk is clearer than relative risk Put the risk is perspective (ie, a risk is “rare” if it occurs <10 per 10,000 patients per year, it’s “very rare” if it occurs <1 per 10,000 patients per year)

47. Explaining Risk (continued) Potential absolute risks for use of HT are low, especially for ET in WHI In WHI, risks for EPT were “rare”, except for stroke For younger women (<50 yrs) or those at low risk of cardiac disease, osteoporosis, breast cancer, or colon cancer, absolute risk is likely to be even smaller than seen in WHI Each regimen, route of administration, and timing of therapy has distinct beneficial and adverse effects

48. HT Risk is Related to… A woman’s baseline disease risks Her age Age at menopause Cause of menopause Time since menopause Prior use of any hormone HT types, routes of administration, and doses used Emerging medical conditions during treatment

49. Summary Menopause is a retrospective diagnosis We serve women best if we individualize discussion and treatment based on symptoms and risk factors Ideal world—few symptoms, and no need for any hormone replacement therapy As women’s life expectancy continues to increase, must look at menopause as third phase of life, and optimize health