Effects of lower doses of conjugated equine estrogens and medroxyprogesterone acetate on endometrial bleeding

Fertil Steril. 2001 Jun;75(6):1080-7. doi: 10.1016/s0015-0282(01)01792-7.


Objective: To evaluate vaginal bleeding profiles with lower doses of conjugated equine estrogens (CEE) and medroxyprogesterone acetate (MPA) as continuous combined therapy.

Design: The Women's Health, Osteoporosis, Progestin, Estrogen (Women's HOPE) study, a randomized, double-blind, placebo-controlled trial.

Setting: Study centers across the United States.

Patient(s): Two thousand six hundred seventy-three healthy, postmenopausal women.

Intervention(s): Women received CEE, 0.625 mg/d; CEE, 0.625 mg/d, plus MPA 2.5 mg/d; CEE, 0.45 mg/d; CEE, 0.45 mg/d, plus MPA, 2.5 mg/d; CEE 0.45 mg/d, plus MPA, 1.5 mg/d; CEE, 0.3 mg/d; CEE, 0.3 mg/d, plus MPA, 1.5 mg/d; or placebo for 1 year.

Main outcome measure(s): Bleeding data were analyzed in efficacy-evaluable and intention-to-treat populations.

Result(s): Cumulative amenorrhea and no bleeding rates were higher with lower doses of CEE/MPA than with CEE 0.625/MPA 2.5. A linear trend between time since menopause and cumulative amenorrhea was observed (P<.05) in all CEE/MPA groups except the CEE 0.45/MPA 1.5 group. The proportion of patients who experienced no bleeding in cycle 1 was 89%, 82%, and 80% in the CEE 0.3/MPA 1.5, CEE 0.45/MPA 1.5, and CEE 0.45/MPA 2.5 groups, respectively. These values were significantly greater than the incidence of no bleeding in the CEE 0.625/MPA 2.5 group (P<.05).

Conclusion(s): Lower-dose regimens of CEE and MPA produce higher rates of amenorrhea and no bleeding compared with CEE 0.625/MPA 2.5 and may be appropriate for newly menopausal patients.

Publication types

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

MeSH terms

  • Amenorrhea / physiopathology
  • Animals
  • Cohort Studies
  • Double-Blind Method
  • Endometrium / blood supply*
  • Estrogens, Conjugated (USP) / administration & dosage*
  • Estrogens, Conjugated (USP) / adverse effects*
  • Female
  • Horses
  • Humans
  • Medroxyprogesterone Acetate / administration & dosage*
  • Medroxyprogesterone Acetate / adverse effects*
  • Treatment Outcome
  • Uterine Hemorrhage / physiopathology*


  • Estrogens, Conjugated (USP)
  • Medroxyprogesterone Acetate