Low-Dose Unopposed Estrogens

Abstract

The objective of this study is to compare the frequency and duration of vaginal bleeding in postmenopausal women randomized to receive unopposed esterified estrogens (ESE) in a dose of 0.3 mg, 0.625 mg, 1.25 mg, or placebo. A two-year randomized, double-blind, placebo-controlled, multicenter study was conducted in 269 non-hysterectomized postmenopausal women who recorded bleeding incidence and severity on diary cards. Amenorrhea occurred in 61% of women receiving placebo and 59%, 51%, and 24% of women treated with 0.3, 0.625, and 1.25 mg ESE, respectively. Combining spotting with amenorrhea, these numbers increased to 88%, 88%, 75%, and 61%, respectively. Onset of menopause greater than 1 year before study entry was associated with less bleeding than onset within 1 year (53% vs. 31%). Treatment with 0.3 mg ESE, a dose that is effective in preventing osteoporosis, did not result in a higher incidence of vaginal bleeding or endometrial hyperplasia than treatment with placebo over a 2-year period. Studies longer than 2 years will be needed to confirm that the beneficial effects on bone can occur without any detrimental endometrial effects.