Long-term safety of unopposed estrogen used by women surviving myocardial infarction: 14-year follow-up of the ESPRIT randomised controlled trial

BJOG. 2014 May;121(6):700-5; discussion 705. doi: 10.1111/1471-0528.12598. Epub 2014 Feb 18.


Objective: To compare health outcomes during 14-year observational follow-up in women initially randomised to unopposed estrogen or placebo.

Design: At recruitment to the Estrogen for the Prevention of Re-Infarction Trial (ESPRIT) women were assigned to estradiol valerate: 2 mg or placebo treatment for 2 years.

Setting: Women were recruited from 35 hospitals in the northwest of England and Wales in July 1996-February 2000.

Sample: Women aged 50-69 surviving their first myocardial infarction.

Methods: All women were followed by data linkage to UK mortality and cancer records; mean follow-up 14.1 and 12.6 years, respectively. In an intention-to-treat analysis, hazard ratios (HRs) were computed, overall and stratified by age at recruitment.

Outcome measures: Death (all-cause, cardiac disease, stroke or cancer) and cancer incidence (any, breast or endometrium).

Results: There were 418 deaths in 1017 women randomised. The all-cause mortality HR of 1.07 (95% CI 0.88-1.29) indicated no significant difference between treatment groups. Women aged 50-59 years at recruitment had lower HRs than women aged 60-69 years for all outcomes except ischaemic heart disease. Among 149 incident cancers there were seven cases of breast cancer in the intervention arm and 15 in the placebo; HR 0.47 (95% CI 0.19-1.15). There were no deaths from endometrial cancer but three incident cases, one in the active arm and two in placebo.

Conclusions: These results suggest that unopposed estrogen may be used safely by women with an intact uterus surviving a first myocardial infarction.

Keywords: Cancer; estrogen; randomised controlled trial.

Publication types

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

MeSH terms

  • Aged
  • Endometrial Neoplasms / prevention & control*
  • England / epidemiology
  • Estrogen Replacement Therapy*
  • Estrogens / administration & dosage*
  • Female
  • Follow-Up Studies
  • Humans
  • Middle Aged
  • Myocardial Infarction / mortality
  • Myocardial Infarction / prevention & control*
  • Postmenopause
  • Risk Factors
  • Secondary Prevention
  • Survivors / statistics & numerical data*
  • Time Factors
  • Treatment Outcome
  • Wales / epidemiology


  • Estrogens