Endometrial effects of lower doses of conjugated equine estrogens and medroxyprogesterone acetate

Objective: To determine the endometrial safety of lower doses of continuous combined conjugated equine estrogens (CEE) and medroxyprogesterone acetate (MPA). Design: Randomized, double-blind, placebo-controlled study (the Women's Hea lth, Osteoporosis, Progestin, Estrogen study). Setting: Study centers across the United States. Patient(s): Healthy, postmenopausal women (n = 2,673) with an intact uterus . Intervention(s): Patients received CEE 0.625 mg/day, CEE 0.625/MPA 2.5 mg/d ay, CEE 0.45 mg/day, CEE 0.45/MPA 2.5 mg/day, CEE 0.45/MPA 1.5 mg/day, CEE 0.3 mg/day, CEE 0.3/MPA 1.5 mg/day, or placebo for 1 year. Endometrial biop sies were evaluated at baseline, cycle 6, and year 1 using a centralized pr otocol. Main Outcome Measure(s): Efficacy of lower doses of CEE/MPA in reducing the incidence of endometrial hyperplasia rates associated with unopposed CEE. Result(s): Endometrial hyperplasia rates ranged from 0 to 0.37% for all CEE /MPA doses. Twenty-nine of the 32 cases of endometrial hyperplasia develope d in women who were administered CEE 0.625 mg or CEE 0.45 mg. The incidence of endometrial hyperplasia increased with age for patients administered CE E alone. As expected, there were some inconsistencies among pathologists' r atings in the numbers of hyperplasias and incidence rates for the CEE-alone regimens. There were too few cases of hyperplasia in the combination group s to evaluate consistency among pathologists. Conclusion(s): One year of treatment with lower doses of CEE/MPA provides e ndometrial protection comparable to commonly prescribed doses. These regime ns may be used by clinicians to individualize hormone replacement therapy i n postmenopausal women. (C) 2001 by American So'iety for Reproductive Medic ine.