Cardiovascular and Other Risks
- Estrogens with or without progestins should not be used for the prevention of cardiovascular disease.
- Estrogens Alone WHI Study-Stroke, DVT:The estrogen alone substudy of the Women's Health Initiative (WHI) Study reported increased risks of stroke and deep vein thrombosis in postmenopausal women (50 to 79 years) during 6.8 and 7.1 years, respectively, of treatment with oral conjugated estrogens (0.625 mg) alone 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)
- Estrogen and progestin combinations increase the risk of thrombotic or thromboembolic disorders, especially in women at increased risk for these events.
- contraindicated in women with current or a history of thrombotic or thromboembolic disorders and in women at increased risk for these events, including women over 35 years of age who smoke or women with uncontrolled hypertension.
Risk of Probable Dementia
- Estrogens with or without progestins should not be used for the prevention of dementia.
- WHIMS Data-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
- In the absence of comparable data, these risks should be assumed to be similar for other doses of conjugated estrogens and medroxyprogesterone 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 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 June 2021