Conjugated equine estrogens and coronary heart disease: the Women's Health Initiative

Arch Intern Med. 2006 Feb 13;166(3):357-65. doi: 10.1001/archinte.166.3.357.


Background: In recent randomized trials, conjugated equine estrogens (CEE) with continuous medroxyprogesterone acetate provided no protection against coronary heart disease in postmenopausal women and may have increased cardiac risk. These trials did not address the role of unopposed estrogen for coronary protection.

Methods: A total of 10 739 women aged 50 to 79 years at baseline (mean age, 63.6 years) who had previously undergone hysterectomy were randomized to receive CEE, 0.625 mg/d, or placebo at 40 US clinical centers beginning in 1993. The trial was terminated early after 6.8 years of follow-up (planned duration, 8.5 years). This report includes final, centrally adjudicated results for the primary efficacy outcome (myocardial infarction or coronary death), secondary coronary outcomes, and subgroup analyses.

Results: During the active intervention period, 201 coronary events were confirmed among women assigned to receive CEE compared with 217 events among women assigned to receive placebo (hazard ratio, 0.95; nominal 95% confidence interval, 0.79-1.16). Among women aged 50 to 59 years at baseline, the hazard ratio for the primary outcome was 0.63 (nominal 95% confidence interval, 0.36-1.08). In that age group, coronary revascularization was less frequent among women assigned to receive CEE (hazard ratio, 0.55; nominal 95% confidence interval, 0.35-0.86), as were several composite outcomes, which included the primary outcome and coronary revascularization (hazard ratio, 0.66; nominal 95% confidence interval, 0.44-0.97).

Conclusions: Conjugated equine estrogens provided no overall protection against myocardial infarction or coronary death in generally healthy postmenopausal women during a 7-year period of use. There was a suggestion of lower coronary heart disease risk with CEE among women 50 to 59 years of age at baseline.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Distribution
  • Aged
  • Blood Glucose / analysis
  • C-Reactive Protein / analysis
  • Cholesterol / blood
  • Estrogens / therapeutic use*
  • Estrogens, Conjugated (USP) / therapeutic use*
  • Female
  • Follow-Up Studies
  • Hormone Replacement Therapy*
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use
  • Insulin / blood
  • Male
  • Middle Aged
  • Myocardial Infarction / epidemiology*
  • Myocardial Infarction / therapy
  • Myocardial Revascularization / statistics & numerical data*
  • Postmenopause
  • Proportional Hazards Models
  • Triglycerides / blood
  • United States / epidemiology


  • Blood Glucose
  • Estrogens
  • Estrogens, Conjugated (USP)
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Insulin
  • Triglycerides
  • C-Reactive Protein
  • Cholesterol