(Circulation. 2005;111:1242-1249.)
© 2005 American Heart Association, Inc.

Epidemiology

Sex Hormone–Binding Globulin and the Free Androgen Index Are Related to Cardiovascular Risk Factors in Multiethnic Premenopausal and Perimenopausal Women Enrolled in the Study of Women Across the Nation (SWAN)

From the Department of Epidemiology (K.S.-T., S.B.), Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pa; Department of Epidemiology (R.P.W.), Tulane University School of Public Health and Tropical Medicine, New Orleans, La; Department of Psychiatry (K.A.M.), University of Pittsburgh School of Medicine, Pittsburgh, Pa; Cardiology Division (C.C., R.C.P.), Massachusetts General Hospital, and Division of Preventive Medicine, Brigham and Women’s Hospital, Boston, Mass; Department of Population Health and Reproduction (B.L.L.), University of California—Davis, Davis, Calif; Feinberg School of Medicine (D.L.-J.), Northwestern University, Chicago, Ill; Department of Epidemiology (M.F.S.), School of Public Health, University of Michigan, Ann Arbor, Mich; and Department of Obstetrics, Gynecology and Women’s Health (J.L.T.), New Jersey Medical School, Newark, NJ.

Correspondence to Kim Sutton-Tyrrell, Department of Epidemiology, University of Pittsburgh, 127 Parran Hall/130 DeSoto St, Pittsburgh, PA 15261. E-mail Tyrrell{}edc.pitt.edu

Received September 17, 2004; revision received December 17, 2004; accepted December 28, 2004.

Background— Recent clinical trials have shifted attention away from estrogens and toward androgens and sex hormone–binding globulin (SHBG) as potential mediators of increasing cardiovascular (CV) risk in women at midlife.

Methods and Results— The correlation between reproductive hormones and CV risk factors was evaluated in a multiethnic (white, black, Hispanic, Chinese, and Japanese) sample of 3297 premenopausal and perimenopausal women. Testosterone and estradiol (E₂) were evaluated along with SHBG and the free androgen index (FAI), the amount of testosterone not bound by SHBG. Low SHBG and high FAI were strongly and consistently related to elevated CV risk factors (higher insulin, glucose, and hemostatic and inflammatory markers and adverse lipids) even after controlling for body mass index (P<0.001 for all). Low levels of E₂ were associated with elevated CV risk factors to a lesser degree. These observations were consistent across the 5 ethnic groups. Compared with whites, blacks had higher levels of SHBG and lower levels of FAI, and Chinese had lower levels of SHBG and higher levels of FAI.

Conclusions— Low SHBG and high FAI are strongly associated with CV risk factors in racially diverse women, and thus, androgens likely play a role in the CV risk profile of perimenopausal women.

Key Words: hormones • aging • sex • menopause • risk factors

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