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Estrogen Therapy and Risk of Cardiovascular Events Among Women With Type 2 Diabetes

¹ Center for Health Studies, Group Health Cooperative, Seattle, Washington
² Department of Epidemiology, University of Washington, Seattle, Washington
³ Fred Hutchinson Cancer Research Center, Seattle, Washington
⁴ Department of Biostatistics, University of Washington, Seattle, Washington

Address correspondence and reprint requests to Katherine M. Newton, PhD, Associate Investigator, Center for Health Studies, 1730 Minor Ave., Suite 1600, Seattle, WA 98101-1448. E-mail: newton.k{at}ghc.org

OBJECTIVE—To evaluate the association between estrogen therapy and cardiovascular disease risk among women with type 2 diabetes.

RESEARCH DESIGN AND METHODS—A retrospective, case-cohort study was conducted among 6,017 women aged 45–80 years with type 2 diabetes from 1 January 1986 to 31 December 1992 at the Group Health Cooperative in Washington state. Cardiovascular outcomes, including nonfatal myocardial infarction (n = 215), coronary revascularization (n = 253), and cardiovascular deaths (n = 229), were ascertained through 31 December 1998. Use of estrogen and progestin was derived from automated pharmacy records and modeled as a time-dependent variable. Median follow-up was 6.8 years. Multivariable-adjusted relative risk (RR) and 95% CI were calculated using Cox proportional hazard models for case-cohort analyses.

RESULTS—Current use of estrogen with (RR 0.43, 95% CI 0.22–0.85) or without (0.48, 0.30–0.78) progestin was associated with a decreased risk of cardiovascular events compared with never having used estrogen. Risk of cardiovascular events associated with a first episode of estrogen use (with or without progestin) of <25 months’ duration (1.12, 0.49–2.54), first episode of use 25 months’ duration (0.32, 0.06–1.70), and current use that was not the first episode of use (0.42, 0.42–0.67) indicated that recent initiation was not associated with an increase or decrease in risk.

CONCLUSIONS—These results show an association of estrogen therapy, with or without progestin, with decreased risk of cardiovascular events among women with type 2 diabetes. This association should be further investigated in large randomized, controlled trials.

Abbreviations: CDS, Chronic Disease Score • GHC, Group Health Cooperative • PEPI, Postmenopausal Estrogen/Progestin Trial

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