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Smith NL, Heckbert SR, Lemaitre RN, et al. Esterified Estrogens and Conjugated Equine Estrogens and the Risk of Venous Thrombosis. JAMA. 2004;292(13):1581–1587. doi:10.1001/jama.292.13.1581
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).
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
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
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