MINIMAL ENDOMETRIAL PROLIFERATION OVER A 2-YEAR PERIOD IN POSTMENOPAUSAL WOMEN TAKING 0.3 MG OF UNOPPOSED ESTERIFIED ESTROGENS

This article reports the endometrial histology of 238 postmenopausal w omen with an intact uterus who were randomized to receive daily admini stration of continuous unopposed esterified estrogens (ESE) in a dose of 0.3 mg, 0.625 mg, 1.25 mg or placebo over a 2-year, prospective, ra ndomized, double-blind, placebo-controlled, clinical trial evaluating osteoporosis prevention. Endometrial hyperplasia occurred in 1.7% of w omen randomized to 0.3 mg ESE (similar to 95% confidence interval, 0.0 0, 0.05), 28.8% of women randomized to 0.625 mg (0.17, 0.40), 53.3% of women randomized to 1.25 mg (0.41, 0.66), and 1.7% of women randomize d to placebo (0.00, 0.05), with no statistical difference between 0.3- mg ESE treatment and placebo. Endometrial proliferation was also dose related, with atrophy occur; ring at termination in only the placebo g roup. The study was completed by 78% of women on the 0.3-mg, 62% on pl acebo, 54% on the 0.625-mg, and 22% on the 1.25mg dose. Endometrial hy perplasia and uterine bleeding primarily contributed to early terminat ions in the higher ESE groups. The incidence of endometrial hyperplasi a during daily administration of 0.3 mg unopposed ESE over a 2-year pe riod was unexpectedly equal to that observed with placebo. The reducti on in endometrial risk, preservation of therapeutic benefit for osteop orosis prevention, and high patient continuation rate achieved by 0.3 mg ESE can be used to maximize the benefits of estrogen on public heal th outcomes.