on September 15, 2003
Published online before print September 15, 2003, doi: 10.1161/01.CIR.0000091114.36254.F3
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Submitted on September 23, 2002
From the Department of Medicine, Division of Preventive Medicine (K.M.R., J.E.M., I.-M.L., P.M.R., N.R.C., J.E.B.), Brigham and Women's Hospital and Harvard Medical School; Department of Epidemiology (J.E.M., I.-M.L., J.E.B.), Harvard School of Public Health; Reproductive Endocrine Unit Assay Laboratory (P.M.S.), Massachusetts General Hospital; and Department of Ambulatory Care and Prevention (J.E.M., J.E.B.), Harvard Medical School, Boston, Mass. * To whom correspondence should be addressed. E-mail: krexrode{at}partners.org.
Background--Despite diffuse effects of sex hormones on the cardiovascular system, few prospective studies have examined the relationship of plasma androgens and estrogens with risk of cardiovascular disease (CVD) in postmenopausal women. Methods and Results--A nested case-control study was performed among women in the Women's Health Study. Two hundred women who developed CVD were matched 1:1 by age, smoking, and postmenopausal hormone therapy (HT) to controls who remained free of CVD. We measured testosterone, estradiol, and sex hormone binding globulin (SHBG) levels and calculated free androgen index (FAI), free estradiol index, and the FAI/free estradiol index ratio. Results were stratified by HT use. Among HT nonusers, cases had significantly higher androgen profiles (higher median FAI and lower SHBG levels) than controls. After adjustment for age, smoking, use of aspirin, vitamin E, and alcohol, family history of myocardial infarction, and physical activity, nonusers in the lowest SHBG quartile had an OR of 2.25 (95% CI, 1.03 to 4.91) for CVD, and there were significant trends across FAI quartiles (P for trend=0.03). Additional adjustment for body mass index, hypertension, diabetes, and elevated cholesterol eliminated associations with SHBG and FAI. Among women using HT, no significant differences in hormones or SHBG were observed among women who developed CVD and controls. Conclusions--Among HT nonusers, lower SHBG and higher FAI levels were noted among postmenopausal women who developed CVD events, but this was not independent of body mass index and other cardiovascular risk factors. Estradiol levels were not associated with risk of CVD in HT users or nonusers.
Revised on July 24, 2003
Accepted on July 26, 2003
Sex Hormone Levels and Risk of Cardiovascular Events in Postmenopausal Women
Kathryn M. Rexrode MD, MPH*,
Key words: hormones • women • cardiovascular diseases • risk factors
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