Conjugated Estrogens/ Combination Meds (Oral)
Cardiovascular; Other Risks
Cardiovascular and Other Risks
- Estrogens plus progestins should not be used for the prevention of cardiovascular disease.
- WHI Study-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)
- WHI Study-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 plus progestins should not be used for the prevention of dementia.
- WHIMS-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 General Risk Statements
- 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.
MONITORING RECOMMENDATIONS RELATED TO BLACK BOX DATA
- Use lowest possible estrogen dose to control symptoms and discontinue medication as soon as possible
- If prolonged treatment indicated, reassess patient on at least a semi-annual basis to determine need for continued therapy
- Close clinical surveillance recommended, monitor for persistent/recurrent abnormal vaginal bleeding.
- Exposure during pregnancy requires patient appraisal of potential risks.
FDA and Industry Communications
Updated May 2019