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.