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

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 pre-existing 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.