Comparison of endometrial growth produced by unopposed conjugated estrogens or by micronized estradiol in postmenopausal women

Objectives: When unopposed estrogen replacement treatment is used, what is the pattern of endometrial growth? Does endometrial growth differ for various dosages and formulations? Study Design: A total of 87 postmenopausal women, median age 57 years (mean 56.7±5.6 years, range 45 to 69 years), were studied in a prospective, randomized, open clinical trial lasting 24 weeks. The treatment arms consisted of micronized estradiol, 0.5 or 1.0 mg (Estrace, Bristol-Myers Squibb, Princeton, N.J.), and conjugated estrogens, 0.625 mg (Premarin, Wyeth-Ayerst, Philadelphia). Endometrial thickness was evaluated by vaginal probe ultrasonography at outset and after 6, 12, and 24 weeks of treatment. Results: Endometrial growth was progressive over time; more than half the total 24-week growth occurred in the first 6 weeks. The mean weekly rate (±SD) of endometrial growth was similar for micronized estradiol, 1.0 mg, and conjugated estrogens, 0.625 mg (0.19±0.15 mm for micronized estradiol, 1.0 mg, and 0.19±0.14 mm for conjugated estrogens, 0.625 mg). These rates differed to a statistically significant degree (p<0.05) from the growth rate produced by micronized estradiol, 0.5 mg (0.08±0.16 mm). Both unscheduled and scheduled uterine bleeding was less likely among women using micronized estradiol, 0.5 mg, than among women using micronized estradiol, 1.0 mg, or conjugated estrogens, 0.625 mg. Conclusions: In a 24-week trial the therapeutically equivalent estrogen doses produced the same mean increment in endometrial thickness, but half-strength estradiol produced half as much endometrial growth.