Conjugated Estrogens/ Combination Meds (Oral)
Endometrial Cancer; Cardiovascular Disorders; Probable Dementia
- There is an increased risk of endometrial cancer in a woman with a uterus who uses unopposed estrogens. Estrogen containing products have been shown to reduce the risk of endometrial hyperplasia, which may be a precursor to endometrial cancer. Adequate diagnostic measures, including directed or random endometrial sampling when indicated, should be undertaken to rule out malignancy in postmenopausal women with undiagnosed persistent or recurring abnormal genital bleeding
- Estrogen therapy should not be used for the prevention of cardiovascular disease or 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 7.1 years of treatment with daily oral conjugated estrogens (0.625 mg)-alone, relative to placebo
- The WHI Memory Study (WHIMS) estrogen-alone ancillary study of WHI reported an increased risk of probable dementia in postmenopausal women 65 years of age and older during 5.2 years of treatment with daily conjugated estrogens (0.625 mg)-alone, relative to placebo. It is unknown whether this finding applies to younger postmenopausal women [see WARNINGS AND PRECAUTIONS (5.4)]
- Only daily oral 0.625 mg CE was studied in the estrogen-alone substudy of the WHI. Therefore, the relevance of the WHI findings regarding adverse cardiovascular events and dementia to lower CE doses, other routes of administration, or other estrogen-alone products is not known. Without such data, it is not possible to definitively exclude these risks or determine the extent of these risks for other products. Discuss with your patient the benefits and risks of estrogen-alone therapy, taking into account her individual risk profile
General Risk Statements
- Women taking estrogen containing products should not take additional estrogens
- Estrogens should be prescribed at the lowest effective doses and for the shortest duration consistent with treatment goals and risks for the individual woman.
MONITORING RECOMMENDATIONS RELATED TO BLACK BOX DATA
- Women taking estrogen containing products patients should not take progestins, additional estrogens or additional estrogen agonist/antagonists
- Monitor for:
Cardiovascular disorders, including venous thromboembolism, pulmonary embolism, stroke, and retinal vascular thrombosis
Malignant neoplasms, including endometrial cancer, breast cancer, and ovarian cancer
Estrogens increase the risk of gallbladder disease
- Discontinue estrogen if loss of vision, severe hypertriglyceridemia or cholestatic jaundice occurs.
- Monitor thyroid function in women on thyroid replacement therapy.
FDA and Industry Communications