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Androgens Are Associated with Hemostatic and Inflammatory Factors among Women at the Mid-Life

Departments of Epidemiology and Biostatistics (M.R.S., M.J., R.L., D.M.), School of Public Health, University of Michigan, Ann Arbor, Michigan 48109; Department of Obstetrics and Gynecology (M.R.S., J.F.R.), University of Michigan, Ann Arbor, MI 48109; University of California Davis (B.L.), Davis, California 95817; University of Pittsburgh (K.S.-T., K.A.M.), Pittsburgh, Pennsylvania 15260; and Merck & Co., Inc. (R.P.), Rahway, New Jersey 08889

Address all correspondence and requests for reprints to: M. R. Sowers, Ph.D., University of Michigan, Department of Epidemiology, School of Public Health, 339 East Liberty Street, Suite 310, Ann Arbor, Michigan 48104. E-mail: mfsowers{at}umich.edu.

Goal: The goal of this study was to relate annually measured endogenous androgens to hemostatic and inflammation markers in women longitudinally.

Methods: A total of 3302 participants from the Study of Women’s Health Across the Nation, aged 42–52 yr at baseline and self-identified as African-American (28%), Caucasian (47%), Chinese (8%), Hispanic (8%), or Japanese (9%) were evaluated for testosterone (T), dehydroepiandrosterone sulfate, and SHBG at four time points in 5 yr. Cardiovascular disease markers were fibrinogen, activated factor VII-c, C-reactive protein (hsC-RP), and the fibrolytic factors, plasminogen activator inhibitor type 1 (PAI-1), and tissue plasminogen activator [t(PA)].

Results: T and free androgen index (FAI) were associated highly positively with PAI-1 and t(PA), and FAI was associated highly and positively with hsC-RP. Lower SHBG levels, associated with greater bioavailable T, were associated significantly with higher levels of PAI-1, t(PA), hsC-RP, and factor VII-c. SHBG was lower in Chinese and Japanese women markedly, resulting in FAI values that, on average, were higher among Chinese and Japanese women compared with African-American, Caucasian, and Hispanic women.

Implications: There were strong, positive associations of androgens with fibrolytic and inflammation markers, even after considering age, body size, smoking, and race/ethnicity. It is important to study androgens, their precursors, and their carrier protein as part of the risk profile for heart disease in mid-aged women.

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