Endometrial Cancer; Cardiovasular; Dementia Risk

Estrogens Increase The Risk of Endometrial Cancer

• Close Clinical surveillance of all women taking estrogens is important.
• Adequate diagnostic measures, including endometrial sampling when indicated, should be undertaken to rule out malignancy in all cases of undiagnosed persistent or recurring abnormal vaginal bleeding.
• There is no evidence that the use of "natural" estrogens results in a different endometrial risk profile than synthetic estrogens at equivalent doses. 

Cardiovascular and Other Risks

• Estrogens with or without progestins should not be used for the prevention of cardiovascular disease.
• Estrogens Alone-Stroke, DVT:The estrogen alone substudy of the Women's Health Initiative reported increased risks of stroke and deep vein thrombosis in postmenopausal women (50 to 79 years) during 6.8 years and 7.1 years, respectively, of treatment with daily oral conjugated estrogens (0.625 mg) per day relative to placebo (See Package Insert)
• Estrogens Plus Progestins-Myocardial infarction, Stroke, Invasive Breast Cancer, Pulmonary Emboli, DVT: The estrogen plus progestin substudy of the Women's Health Initiative reported increased risks of myocardial infarction, stroke, invasive breast cancer, pulmonary emboli, and deep vein thrombosis in postmenopausal women (50 to 79 years) during 5.6 years of treatment with daily oral conjugated estrogens (0.625 mg) combined with medroxyprogesterone acetate (MPA 2.5 mg) per day relative to placebo (See Package Insert)

Risk of Probable Dementia

• Estrogens with or without progestins should not be used for the prevention of dementia.
• Estrogens Plus Progestins-Dementia: The Women's Health Initiative Memory Study (WHIMS), a substudy of WHI, reported an increased risk of developing probable dementia in postmenopausal women 65 years of age or older during 5.2 years of treatment with conjugated estrogens 0.625 mg alone and during four years of treatment with daily conjugated estrogens 0.625 mg combined with medroxyprogresterone acetate 2.5 mg, relative to placebo. It is unknown whether this finding applies to younger postmenopausal women. (See package insert)
  Other Risk
• Other doses of conjugated estrogens and medroxyprogesterone acetate, and other combinations and dosage forms of estrogens and progestins, were not studied in the WHI clinical trials, and in the absence of comparable data, these risks should be assumed to be similar.
• Because of these risks, estrogens with or without progestins should be prescribed at the lowest effective doses and for the shortest duration consistent with treatment goals for the individual woman.