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REVIEW

Postmenopausal Estrogen Replacement and Risk for Venous Thromboembolism

A Systematic Review and Meta-Analysis for the U.S. Preventive Services Task Force

Jill Miller, MD; Benjamin K.S. Chan, MS; and Heidi D. Nelson, MD, MPH

7 May 2002 | Volume 136 Issue 9 | Pages 680-690

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.

Author and Article Information

From Veterans Affairs Medical Center and Oregon Health & Science University, Portland, Oregon.

Acknowledgments: The authors thank Steven Teutsch, MD, MPH, and Janet Allan, PhD, RN, from the U.S. Preventive Services Task Force and Mark Helfand, MD, MS, from the Evidence-Based Practice Center for their helpful comments on earlier versions of this review. They also thank Peggy Nygren, MA, for assistance with manuscript preparation.

Grant Support: By the Oregon Health & Science University Evidence-Based Practice Center, under contract (no. 290-97-0018, task order no. 2) to the Agency for Healthcare Research and Quality. Additional support came from the Portland Veterans Affairs Medical Center Women's Health Fellowship.

Requests for Single Reprints: Jill Miller, MD, Oregon Health & Science University, Mail Code BICC 504, 3181 SW Sam Jackson Park Road, Portland, OR 97201.

Current Author Addresses: Drs. Miller and Nelson and Mr. Chan: Oregon Health & Science University, Mail code BICC 504, 3181 Southwest Sam Jackson Park Road, Portland, OR 97201.

Related articles in Annals:

Summaries for Patients
Postmenopausal Estrogen Replacement Therapy and the Risk for Blood Clots: A Review from the U.S. Preventive Services Task Force

Annals 2002 136: I42. [Full Text]  

Letters
Correction: Postmenopausal Estrogen Replacement and Risk for Venous Thromboembolism

Annals 2003 138: 360. [Full Text]  

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