Postmenopausal estrogen replacement and risk for venous thromboembolism: a systematic review and meta-analysis for the U.S. Preventive Services Task Force

Ann Intern Med. 2002 May 7;136(9):680-90. doi: 10.7326/0003-4819-136-9-200205070-00011.


Background: Postmenopausal estrogen replacement is widely used in the United States but poses important health risks.

Purpose: To assess the risk for venous thromboembolism with postmenopausal estrogen replacement by using literature review and meta-analysis.

Data sources: All relevant English-language studies identified in searches of the MEDLINE (1966 to December 2000), HealthSTAR (1975 to December 2000), and Cochrane Library databases, and references lists of key articles.

Study selection: All published studies of postmenopausal estrogen replacement reporting venous thromboembolism as an outcome or adverse event.

Data extraction: 12 studies of estrogen were identified (3 randomized, controlled trials; 8 case-control studies; and 1 cohort study). Data were extracted on participants, interventions, event rates, and confounders. Two reviewers independently rated study quality on the basis of established criteria.

Data synthesis: A Bayesian meta-analysis was conducted. When data from all studies were pooled, current estrogen use was associated with an increased risk for venous thromboembolism (relative risk, 2.14 [95% credible interval, 1.64 to 2.81]). Estimates did not significantly change when studies were pooled according to study design, quality score, or whether participants had preexisting coronary artery disease. The absolute rate increase was 1.5 venous thromboembolic events per 10 000 women in 1 year. Six case-control studies that reported risk according to duration of use found that risk was highest in the first year of use (relative risk, 3.49 [credible interval, 2.33 to 5.59]).

Conclusion: Postmenopausal estrogen replacement is associated with an increased risk for venous thromboembolism, and this risk may be highest in the first year of use.

Publication types

  • Meta-Analysis
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.
  • Review
  • Systematic Review

MeSH terms

  • Bayes Theorem
  • Case-Control Studies
  • Cohort Studies
  • Estrogen Replacement Therapy / adverse effects*
  • Female
  • Humans
  • Postmenopause*
  • Randomized Controlled Trials as Topic
  • Risk Factors
  • Thromboembolism / epidemiology
  • Thromboembolism / etiology*
  • Time Factors
  • United States / epidemiology