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

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)

Epidemiology

Born Life Span

Years in Menopa

use

1850 45 0

1900 50 0

1950 70 19

1960 73 22

1970 75 24

1980 79 28

1990 80 30

2000 80 30+

0

10

20

30

40

50

60

70

80

1850 1850 1950 1970 1990

Life Span

Yrs. In Men

3-D Column 3

Primary Symptoms of Menopause

Cycle changes Oligoamenorrhea – amenorrhea Vasomotor Vaginal dryness

Secondary Symptoms of Menopause

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

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

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

Consequences and Impact of Estrogen Loss

Hot flashes Sleep disturbance Urogenital Atrophy Osteoporosis Skin Dryness Aging

Managment

Hormone therapy Alternative therapy Grin and bear it

Estrogen/Progesterone TherapyPotential Risks and Concerns

Women’s health initiative study Breast cancer Cardio vascular disease Venous thrombosis Endometrial cancer Compliance/therapy

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

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

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

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

Women’s Health InitiativeClinical Outcomes

Outcome Placebo HRT Additional

(fewer) Cases

Hazard

Ratio

CHD 30 37 +7 1.29

Stroke 21 29 +8 1.41

Pulmonary Embolism

8 16 +8 2.13

Breast Cancer 30 38 +8 1.26

Hip Fracture 15 10 -5 0.66Colon Cancer 16 10 -6 0.63

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

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

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

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

Outcomes Changes Vs Placebo after nearly 7 years

CHD No increased or decreased overall risk

Breast Cancer No increased risk

Stroke Increased risk

Hip Fractures Decreased risk

Probable Dementia and Mild Cognitive Impairment

Trend Toward Increased Risk

Summary (WHI Trials)

E/P E/Only

Breast CA Significant increased risk

Did not detect increased risk

Coronary heart disease events

Significant increased risk

Did not detect increased risk

Hip fractures Decreased risk Decreased risk

Colon cancer Decreased risk Decreased risk

Stroke Increased risk Increased risk

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

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

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

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

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