Context: Although postmenopausal hormone replacement therapy is widely used, its risks and benefits are not well understood.
Objective: To assess the risk of venous thromboembolism with the use of postmenopausal hormone replacement therapy (HRT) by literature review and meta-analysis.
Data Sources: All relevant English-language studies identified in MEDLINE (1966 to December 2000), HealthSTAR (1975 to December 2000), Cochrane library databases, and reference lists of key articles. Studies of selective estrogen receptor modulators (SERMs) were identified in MEDLINE (1991 to December 2000).
Study Selection: All studies of postmenopausal HRT or SERMs reporting venous thromboembolism as an outcome or adverse event.
Data Extraction: Twelve studies of HRT (3 randomized controlled trials, 8 case-control studies, and one cohort study), and 5 randomized controlled trials of SERMs were identified. We extracted data on number of participants, interventions, event rates, and confounders. Two reviewers independently rated study quality based on established criteria.
Data Synthesis: We used Bayesian meta-analysis. Current HRT use was associated with an increased risk of venous thromboembolism (relative risk [RR], 2.14; CI, 1.64-2.81). The absolute rate increase was 1.5 venous thromboembolic events per 10,000 women in one year. Five case-control studies reported highest risk within the first year of use (odds ratios [OR], 2.9-6.7). Data from 5 randomized controlled trials of SERMs were not included in the meta-analysis. The 2 largest trials reported a similar increased risk of venous thromboembolism.
Conclusions: Postmenopausal HRT is associated with an increased risk of venous thromboembolism, and this risk may be highest in the first year of use. SERMs are associated with a similar increase in risk.