Objective: To determine the endometrial safety of 2 years of treatment with lower doses of continuous combined conjugated equine estrogens (CEE) and medroxyprogesterone acetate (MPA).
Design: Randomized, double-blind, placebo-controlled, multicenter metabolic and osteoporosis substudy of the Women's Health, Osteoporosis, Progestin, Estrogen (Women's HOPE) study.
Setting: Nineteen study centers across the United States.
Patient(s): Healthy, postmenopausal women (n = 822) with an intact uterus were recruited.
Intervention(s): Patients received CEE 0.625, CEE 0.625/MPA 2.5, CEE 0.45, CEE 0.45/MPA 2.5, CEE 0.45/MPA 1.5, CEE 0.3, CEE 0.3/MPA 1.5 (all doses mg/day), or placebo for 2 years. Endometrial biopsies were evaluated at baseline and years 0.5, 1, 1.5, and 2 using a centralized protocol.
Main outcome measure(s): Efficacy of lower doses of CEE/MPA in reducing the incidence of endometrial hyperplasia rates associated with unopposed estrogen (E).
Result(s): No cases of endometrial hyperplasia were seen in the four CEE/MPA groups. For the CEE-alone groups, a dose-related increase in incidence rates from 3.17% (CEE 0.3 mg) to 27.27% (CEE 0.625 mg) was seen at 2 years. The number of cases increased from year 1 to year 2. For the CEE-alone groups, the incidence rates and types of hyperplasia diagnosed varied among the pathologists.
Conclusion(s): Two years of treatment with lower doses of CEE/MPA provided endometrial protection comparable to that seen with commonly prescribed doses. These regimens should be considered for postmenopausal women who are candidates for hormone therapy.