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Published on : Jan 08, 2015
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Slide 1 - Menopause Paul Beck, MD, FACOG, FACS
Slide 2 - What is Menopause Loss of ovarian activity – loss of menses Loss of estrogen-significant impact Life span in menopause – 1/3 to ½
Slide 3 - Menopause Demographics 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)
Slide 4 - Epidemiology
Slide 5 - Primary Symptoms of Menopause Cycle changes Oligoamenorrhea – amenorrhea Vasomotor Vaginal dryness
Slide 6 - Secondary Symptoms of Menopause Urinary – stress/urge incontinence Frequency – burning ( cystitis) Psychophysiologic changes Musculoskeletal pains Decrease concentration Decreased libido
Slide 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
Slide 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
Slide 9 - Consequences and Impact of Estrogen Loss Hot flashes Sleep disturbance Urogenital Atrophy Osteoporosis Skin Dryness Aging
Slide 10 - Managment Hormone therapy Alternative therapy Grin and bear it
Slide 11 - Estrogen/Progesterone Therapy Potential Risks and Concerns Women’s health initiative study Breast cancer Cardio vascular disease Venous thrombosis Endometrial cancer Compliance/therapy
Slide 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
Slide 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
Slide 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
Slide 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
Slide 16 - Women’s Health Initiative Clinical Outcomes
Slide 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
Slide 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
Slide 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
Slide 20 - WHI Preliminary Findings for Estrogen Alone – As Reported by the NIH
Slide 21 - Summary (WHI Trials)
Slide 22 - Alternative Measures Vasomotor 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
Slide 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
Slide 24 - Menopause Preventing 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
Slide 25 - Menopause Preventing 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
Slide 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