Menopause

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Menopause

• Paul Beck, MD, FACOG, FACS

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What is Menopause

• Loss of ovarian activity loss of menses
• Loss of estrogen-significant impact
• Life span in menopause 1/3 to ½

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MenopauseDemographics

• 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)

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Epidemiology

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Primary Symptoms of Menopause

• Cycle changes
• Oligoamenorrhea amenorrhea
• Vasomotor
• Vaginal dryness

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Secondary Symptoms of Menopause

• Urinary stress/urge incontinence
• Frequency burning ( cystitis)
• Psychophysiologic changes
• Musculoskeletal pains
• Decrease concentration
• Decreased libido

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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

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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

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Consequences and Impact of Estrogen Loss

• Hot flashes
• Sleep disturbance
• Urogenital Atrophy
• Osteoporosis
• Skin Dryness
• Aging

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Managment

• Hormone therapy
• Alternative therapy
• Grin and bear it

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Estrogen/Progesterone TherapyPotential Risks and
Concerns

• Womens health initiative study
• Breast cancer
• Cardio vascular disease
• Venous thrombosis
• Endometrial cancer
• Compliance/therapy

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WHI Objective

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

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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

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WHI Continued

• No substantive difference between groups at
  baseline
• Mean age 63.2 for EP group
• Mean age 63.3 for placebo group
• 2/3 between 60 and 79 years

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WHI Status

• EP 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

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Womens Health InitiativeClinical Outcomes
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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

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Womens 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 Womens Health Initiative
  Investigators
• JAMA 2002288321-333

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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

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WHI Preliminary Findings for Estrogen Alone As
Reported by the NIH
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Summary (WHI Trials)
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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

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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. Johns 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

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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

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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

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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