There is an increased risk of endometrial cancer in a woman with a uterus who uses unopposed estrogens. Adding a progestin to estrogen therapy has 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.
Estrogens with or without progestins 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 with daily oral conjugated estrogens (CE) alone. The WHI estrogen plus progestin substudy reported increased risks of DVT, pulmonary embolism, stroke, and myocardial infarction in postmenopausal women with daily oral CE combined with medroxyprogesterone acetate (MPA). In the absence of comparable data, these risks should be assumed to be similar for other dosage forms of estrogens.
The WHI Memory Study (WHIMS) reported an increased risk of developing probable dementia in postmenopausal women 65 years of age or older, in both the estrogen-alone and estrogen plus progestin arms. It is unknown whether these findings apply to younger postmenopausal women.
The WHI estrogen plus progestin substudy demonstrated an increased risk of invasive breast cancer.
Estrogens with or without progestins should be prescribed at the lowest effective dose and for the shortest duration consistent with treatment goals and risks for the individual woman.
ESTRING should not be used in women with any of the following conditions: undiagnosed abnormal genital bleeding; known, suspected, or a history of breast cancer; known or suspected estrogen-dependent neoplasia; active DVT, pulmonary embolism, or a history of these conditions; active arterial thromboembolic disease (eg, stroke, myocardial infarction), or a history of these known conditions; anaphylactic reaction or known hypersensitivity to ESTRING; liver dysfunction or disease; known protein C, protein S, or antithrombin deficiency, or other known thrombophilic disorders; known or suspected pregnancy.
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, because estrogens may be associated with increased thyroid-binding globulin (TBG) levels.
The most frequently reported adverse events associated with ESTRING were headache, leukorrhea, back pain, genital moniliasis, upper respiratory tract infection, vaginitis, and vaginal discomfort/pain.
ESTRING is indicated for the treatment of moderate-to-severe symptoms of vulvar and vaginal atrophy due to menopause.
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