Estradiol Valerate (Injectable)
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 estrogen doses.
Cardiovascular and Other Risks
- Estrogens and progestins should not be used for the prevention of cardiovascular disease.
- MI, Stroke, Breast Cancer, PE, DVT:The Women's Health Initiative (WHI) 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 yrs of treatment with daily oral conjugated estrogens (0.625 mg) combined with medroxyprogesterone acetate (MPA 2.5 mg) relative to placebo (See Package Insert)
- 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.
- Only daily oral oral 0.625 mg CE and 2.5 mg MPA were studied in the estrogen plus progestin substudy of the WHI. Therefore, the relevance of the WHI findings regarding adverse cardiovascular events, dementia and breast cancer to lower CE plus other MPA doses, other routes of administration, or other estrogen plus progestin 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 plus progestin therapy, taking into account her individual risk profile.
Risk of Probable Dementia
- WHIMS Study: 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 four years of treatment with daily conjugated estrogens combined with medroxyprogresterone acetate, relative to placebo. It is unknown whether this finding applies to younger postmenopausal women. (See package insert)
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 January 2020