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Esterified Estrogens and Conjugated Equine Estrogens and the Risk of Venous Thrombosis
Nicholas L. Smith, PhD;
Susan R. Heckbert, MD, PhD;
Rozenn N. Lemaitre, PhD;
Alex P. Reiner, MD, MPH;
Thomas Lumley, PhD;
Noel S. Weiss, MD, DrPH;
Eric B. Larson, MD, MPH;
Frits R. Rosendaal, MD;
Bruce M. Psaty, MD, PhD
JAMA. 2004;292:1581-1587.
Context Clinical trial evidence indicates that estrogen therapy with or without progestins increases venous thrombotic risk. The findings from these trials, which used oral conjugated equine estrogens, may not be generalizable to other estrogen compounds.
Objective To compare risk of venous thrombosis among esterified estrogen users, conjugated equine estrogen users, and nonusers.
Design, Setting, and Participants This population-based, case-control study was conducted at a large health maintenance organization in Washington State. Cases were perimenopausal and postmenopausal women aged 30 to 89 years who sustained a first venous thrombosis between January 1995 and December 2001 and controls were matched on age, hypertension status, and calendar year.
Main Outcome Measure Risk of first venous thrombosis in relation to current use of esterified or conjugated equine estrogens, with or without concomitant progestin. Current use was defined as use at thrombotic event for cases and a comparable reference date for controls.
Results Five hundred eighty-six incident venous thrombosis cases and 2268 controls were identified. Compared with women not currently using hormones, current users of esterified estrogen had no increase in venous thrombotic risk (odds ratio [OR], 0.92; 95% confidence interval [CI], 0.69-1.22). In contrast, women currently taking conjugated equine estrogen had an elevated risk (OR, 1.65; 95% CI, 1.24-2.19). When analyses were restricted to estrogen users, current users of conjugated equine estrogen had a higher risk than current users of esterified estrogen (OR, 1.78; 95% CI, 1.11-2.84). Among conjugated equine estrogen users, increasing daily dose was associated with increased risk (trend P value = .02). Among all estrogen users, concomitant progestin use was associated with increased risk compared with use of estrogen alone (OR, 1.60; 95% CI, 1.13-2.26).
Conclusion Our finding that conjugated equine estrogen but not esterified estrogen was associated with venous thrombotic risk needs to be replicated and may have implications for the choice of hormones in perimenopausal and postmenopausal women.
Author Affiliations: Departments of Epidemiology (Drs Smith, Heckbert, Reiner, Weiss, and Psaty), Medicine (Drs Lemaitre and Psaty), Biostatistics (Dr Lumley), and Health Services (Dr Psaty), University of Washington, Seattle; Center for Health Studies, Group Health Cooperative, Seattle, Wash (Drs Heckbert, Larson, and Psaty); and Leiden University Medical Center, Leiden, the Netherlands (Dr Rosendaal).
Corresponding Author: Nicholas L. Smith, PhD, Cardiovascular Health Research Unit, 1730 Minor Ave, Suite 1360, Seattle, WA 98101 (nlsmith{at}u.washington.edu).
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