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Menopause

Menopause. Paul Beck, MD, FACOG, FACS. What is Menopause. Loss of ovarian activity – loss of menses Loss of estrogen-significant impact Life span in menopause – 1/3 to ½. 42 million women over age 50 52 million by 2010 8.8 million women age 50 to 54

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Menopause

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  1. Menopause Paul Beck, MD, FACOG, FACS

  2. What is Menopause • Loss of ovarian activity – loss of menses • Loss of estrogen-significant impact • Life span in menopause – 1/3 to ½

  3. 42 million women over age 50 52 million by 2010 8.8 million women age 50 to 54 Average age at menopause 51.4 years (range – 45 to 55 years) MenopauseDemographics

  4. Epidemiology

  5. Primary Symptoms of Menopause • Cycle changes • Oligoamenorrhea – amenorrhea • Vasomotor • Vaginal dryness

  6. Secondary Symptoms of Menopause • Urinary – stress/urge incontinence • Frequency – burning ( cystitis) • Psychophysiologic changes • Musculoskeletal pains • Decrease concentration • Decreased libido

  7. Actions of Estrogen • Development of ovaries, tubes, uterus and vagina • Secondary sexual characteristics • HPO axis interaction • Proliferative changes in the endometrium • Increases fat deposition and vascular profusion of skin

  8. Actions of Progesterone Specific • Interacts with hypothalmus and pituitary to regulate menstrual cycle • Produces secretory changes in the endometrium • Increases viscosity of cervical mucus • Prepares breast for lactation during pregnancy

  9. Consequences and Impact of Estrogen Loss • Hot flashes • Sleep disturbance • Urogenital Atrophy • Osteoporosis • Skin Dryness • Aging

  10. Managment • Hormone therapy • Alternative therapy • Grin and bear it

  11. Estrogen/Progesterone TherapyPotential Risks and Concerns • Women’s health initiative study • Breast cancer • Cardio vascular disease • Venous thrombosis • Endometrial cancer • Compliance/therapy

  12. WHI Objective • Assess benefits and risks of the most commonly used E/P combination in the US • 16,608 women randomized • 8, 506 – E+P (.625 CEE + 2.5 MP) • 8, 102 – placebo • Planned duration 8.5 years • Post menopausal women age 50 – 79 years

  13. WHI Main Outcome Measures • Primary outcome coronary heart disease (CHD): non-fatal myocardial infarction and CHD death • Primary adverse outcome invasive breast cancer • Secondary outcomes stoke pulmonary embolism endometrial cancer cholorectal cancer hip fracture death due to other causes

  14. WHI Continued • No substantive difference between groups at baseline • Mean age 63.2 for E+P group • Mean age 63.3 for placebo group • 2/3 between 60 and 79 years

  15. WHI Status • E+P study stopped early – 531 2002, mean 5.2 years • Reason – increase in invasive breast cancer exceeded the safety boundary for harm • Evidence for some increase in CHD, stroke and pulmonary embolism • Outweighed evidence fracture decrease • Unopposed estrogen study continued

  16. Women’s Health InitiativeClinical Outcomes

  17. WHI Time Trends • CHD began to develop soon after randomization (first year) • Breast Cancer – comparable through first four years then curve for estrogen began to rise more rapidly then placebo • 5.2 years sharper increase- more pronounced

  18. Women’s Heath Initiative Primary Conclusion “The risk-benefit profile found in this trial is not consistent with the requirements for a viable intervention for primary prevention of chronic diseases, and the results indicate that this regiment should not be initiated or continued for primary prevention of CHD.” Writing Group for the Women’s Health Initiative Investigators JAMA 2002;288:321-333

  19. WHI Implications/Limitations • Absolute risks –small-previously described • E/PT for treatment of menopausal symptoms not evaluated • Only one drug used not comparable for other E/PTs

  20. WHI Preliminary Findings for Estrogen Alone – As Reported by the NIH

  21. Summary (WHI Trials)

  22. Alternative MeasuresVasomotor Symptoms • Progesterone/oral and transdermal works/adverse affect on lipid profile • Micronized natural plant progesterone – no adverse effect on lipid profile – no trials regarding vasomotor symptoms • Exercise –beneficial (selection bias) • Soy – significant reduction in hot flashes- requires large amounts – lowers LDL

  23. Vasomotor Symptoms(continued) • Black Cohosh: significant improvement • Dong Quai: no improvement when used alone • Evening Primrose Oil: no more effective than placebo • Antidepressants: SSRIs – 50% improvement • St. John’s Wort: use in mild depression beneficial – for menopausal symptoms – questionable efficacy • Other Herbal Supplements/Homeopathy: flaxseed oil, fish oil, omega 3, red clover, ginseng, rice bran oil, wild yam, calcium, gotukola, licorice root, sage, sarsaparilla, passion flower, ginkgo biloba and valerian root – no evidence

  24. MenopausePreventing Cardiovascular Disease • Soy: claim based on lipid lowering effects • Vitamin C, E, and B Carotene: no good evidence • Fish Oil: Omega-3 fatty acids and N-3 polyunsaturated fatty acids – effective for secondary prevention of cardiac events – no large trials as a means of primary prevention in postmenopausal women who are at risk • Red Clover: does not improve plasma lipids- no long term studies

  25. MenopausePreventing Bone Loss • Soy: (i.e., isoflavone) - small studies on postmenopausal women show increase in lumbar spine BMD – no difference in hip • Hip Fracture: no studies documenting reduction • Magnesium: deficiency may contribute to decreased BMD

  26. Summary • Black Cohosh: good for vasomotor symptoms • Soy: good for VMS –bone – lowers lipid levels • Exercise: good for VMS • Fish Oil: good for secondary prevention of cardiac events, not VMS • Magnesium: good for bone density – no evidence of prevention of hip fractures

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