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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2006;26:2807.)
© 2006 American Heart Association, Inc.

Thrombosis

Conjugated Equine Estrogen, Esterified Estrogen, Prothrombotic Variants, and the Risk of Venous Thrombosis in Postmenopausal Women

Nicholas L. Smith; Susan R. Heckbert; Rozenn N. Lemaitre; Alexander P. Reiner; Thomas Lumley; Frits R. Rosendaal; Bruce M. Psaty

From Department of Epidemiology (N.L.S., S.R.H., A.P.R., B.M.P.), Medicine (R.N.L., B.M.P.), Biostatistics (T.L.), and Health Services (B.M.P.), University of Washington, Seattle; and the Department of Clinical Epidemiology (F.R.R.) and Hematology (F.R.R.), Leiden University Medical Center, Leiden, the Netherlands.

Correspondence to Nicholas L. Smith, PhD, Cardiovascular Health Research Unit, University of Washington, 1730 Manor Avenue, Suite 1360, Seattle, WA 98101. E-mail nlsmith{at}u.washington.edu

Background— Joint exposure to oral conjugated equine estrogen (CEE) and prothrombotic genetic variants factor II G20210A or factor V G1601A (Leiden) increase venous thrombotic risk 6- to 16-fold in postmenopausal women. Esterified estrogen (EE), an alternative estrogenic compound, appears not to be associated with increased risk and nothing is known about the joint risk with prothrombotic genetic variants.

Methods and Results— We conducted a population-based, case-control study among postmenopausal women within a health maintenance organization. Subjects included 328 cases who sustained a first venous thrombosis and 1591 controls. Current hormone use was defined using electronic pharmacy records and variants FII G20210A and FV Leiden were genotyped using blood samples. FII and FV Leiden variants were associated with 2.1-fold and 3.7-fold increases in venous thrombotic risk, respectively. Overall, CEE use was associated with a 2.5-fold increase in risk compared with no hormone use, whereas EE use was not associated with a statistically increased risk. Compared with no hormone use and no variant, joint exposure to CEE and either prothrombotic variant was associated with an odds ratio (OR) of 9.1 (95% CI: 4.5 to 18.2), whereas joint exposure to EE and either variant was associated with an OR of 2.1 (0.6 to 6.8). When analyses were restricted to hormone users with either variant, CEE use was associated with an OR of 5.3 (1.3 to 21.7) compared with EE use.

Conclusions— These findings need replication and suggest EE use is associated with less risk than CEE use especially among 5% to 10% of women who are carriers of a prothrombotic variant.

Joint exposure to conjugated equine estrogen (CEE) and prothrombotic genetic variants increase venous thrombotic risk. Esterified estrogen (EE) is not associated with risk and nothing is known about joint risks with prothrombotic variants. Findings suggest EE is associated with less risk than CEE especially among carriers of prothrombotic variants.

Key Words: epidemiology • genetics • hormones • venous thrombosis • women