Esterified estrogens and conjugated equine estrogens and the risk of venous thrombosis

Abstract

Conclusion: Equine-derived estrogens, but not esterified estrogens, are associated with increased venous thromboembolic (VTE) risk in perimenopausal and postmenopausal women. Summary: Clinical trials indicating increased VTE risk associated with perimenopausal and postmenopausal estrogen supplementation have employed oral conjugated equine estrogens. The authors sought to determine whether these findings also apply to other estrogen compounds. They compared risk of VTE among users of conjugated equine estrogens, esterified estrogens, and nonestrogen users. This was a population-based, case-control study conducted among patients of a large health maintenance organization. The cases included perimenopausal and postmenopausal women aged 30 to 89 years who had a first episode of VTE from January 1995 to December 2001. The controls were matched by age, hypertension status, and calendar year. The main outcome measure was the risk of first VTE with respect to use of esterified or conjugated equine estrogens with or without progestin. The authors identified 586 first-time VTE cases and 2,268 controls. Current users of esterfied estrogen had no increase in VTE risk (odds ratio [OR], 0.92; 95% confidence interval [CI], 0.69 to 1.22) compared with controls. Women taking conjugated equine estrogen had an elevated risk (OR, 1.65; 95% CI, 1.24 to 2.19). Users of conjugated equine estrogen had a higher risk of VTE than users of esterified estrogen (OR, 1.78; 95% CI, 1.11 to 2.84). An increased daily dose of conjugated equine estrogen was associated with increased risk (trend P = .02). Among users of conjugated equine estrogen and esterified estrogen, use of progestin was associated with an increased risk compared with use of estrogen alone (OR, 1.60; 95% CI, 1.13 to 2.26). Comment: Just as all quarterbacks and surgeons are not equal, it also appears that estrogens, when used in perimenopausal and postmenopausal women, are also not all the same. This study has significant implications for potential selection of perimenopausal and postmenopausal hormone therapy and may modify the implications of the findings of increased VTE risk associated with estrogen therapy in The Women’s Health Initiative Study. (See abstract Estrogen Plus Progestin and Risk of Venous Thrombosis in this month’s abstract section of the journal.)