Endometrial effects of lower doses of conjugated equine estrogens and medroxyprogesterone acetate: two-year substudy results

Fertil Steril. 2003 Nov;80(5):1234-40. doi: 10.1016/s0015-0282(03)01167-1.

Abstract

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.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Drug Therapy, Combination
  • Endometrial Hyperplasia / epidemiology*
  • Estrogen Replacement Therapy*
  • Estrogens / administration & dosage*
  • Estrogens, Conjugated (USP) / administration & dosage*
  • Female
  • Humans
  • Incidence
  • Medroxyprogesterone Acetate / administration & dosage*
  • Middle Aged
  • Placebos

Substances

  • Estrogens
  • Estrogens, Conjugated (USP)
  • Placebos
  • Medroxyprogesterone Acetate