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

James H. Pickar, I. Tien Yeh, James E. Wheeler, Mary F. Cunnane, Leon Speroff

Research output: Contribution to journalArticlepeer-review

101 Scopus citations


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 Health, 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/day, 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 biopsies were evaluated at baseline, cycle 6, and year 1 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 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 developed 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 CEE alone. As expected, there were some inconsistencies among pathologists' ratings in the numbers of hyperplasias and incidence rates for the CEE-alone regimens. There were too few cases of hyperplasia in the combination groups to evaluate consistency among pathologists. Conclusion(s): One year of treatment with lower doses of CEE/MPA provides endometrial protection comparable to commonly prescribed doses. These regimens may be used by clinicians to individualize hormone replacement therapy in postmenopausal women.

Original languageEnglish (US)
Pages (from-to)25-31
Number of pages7
JournalFertility and sterility
Issue number1
StatePublished - 2001


  • Conjugated equine estrogens (CEE)
  • Endometrial hyperplasia
  • Hormone replacement therapy (HRT)
  • Lower HRT doses
  • Medroxyprogesterone acetate (MPA)
  • Menopause
  • Postmenopausal women
  • Women's HOPE Study

ASJC Scopus subject areas

  • Reproductive Medicine
  • Obstetrics and Gynecology


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