WARNINGS
ENDOMETRIAL CANCER
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. (See WARNINGS, Malignant neoplasms, Endometrial cancer.)
CARDIOVASCULAR AND OTHER RISKS
Estrogens with or without progestins should not be used for the prevention of cardiovascular
disease or dementia. (See CLINICAL STUDIES and WARNINGS, Cardiovascular disorders and Dementia.)
The Women’s Health Initiative (WHI) estrogen alone substudy reported increased risks of stroke
and deep vein thrombosis (DVT) in postmenopausal women (50 to 79 years of age) during 6.8 years
and 7.1 years, respectively, of treatment with daily oral conjugated estrogens (CE 0.625 mg)
relative to placebo. (See CLINICAL STUDIES and WARNINGS, Cardiovascular disorders.)
The estrogen plus progestin WHI substudy reported increased risks of myocardial infarction,
stroke, invasive breast cancer, pulmonary emboli, and DVT in postmenopausal women (50 to 79 years
of age) during 5.6 years of treatment with daily oral CE 0.625 mg combined with medroxyprogesterone
acetate (MPA 2.5 mg), relative to placebo. (See CLINICAL STUDIES and WARNINGS, Cardiovascular disorders
and Malignant neoplasms, Breast cancer.)
The Women’s Health Initiative Memory Study (WHIMS), a substudy of the WHI, reported increased risk
of developing probable dementia in postmenopausal women 65 years of age or older during 5.2 years
of treatment with daily CE 0.625 mg alone and during 4 years of treatment with daily CE 0.625 mg
combined with MPA 2.5 mg, relative to placebo. It is unknown whether this finding applies to
younger postmenopausal women. (See CLINICAL STUDIES and WARNINGS, Dementia and PRECAUTIONS,
Geriatric Use.)
In the absence of comparable data, these risks should be assumed to be similar for other doses of
CE and MPA and other combinations and dosage forms of estrogens and progestins. 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 and risks for the individual woman.