Background: Body mass index (BMI) is directly related to testosterone (total T and free T) and inversely to SHBG cross-sectionally, but little is known about how changes in body fat and androgen markers affect each other over time. Methods: Participants included 969 White and Black women from the Coronary Artery Risk Development in Young Adults (CARDIA) cohort, who were ages 18-30 at entry into the study and were pre- or perimenopausal 16 yr later at the time of the CARDIA Women's Study (CWS). Total T and SHBG were assayed from specimens drawn at the CWS examination and stored serum from the yr 2 and 10 CARDIA exams. Free T was calculated based on total T and SHBG. BMI and waist circumference were measured at yr 2, 10, and 16. Results: Despite clinically significant increases in BMI and waist circumference, total T and free T tended to decline, whereas SHBG remained relatively constant. BMI and waist circumference were directly correlated with free T and inversely correlated with SHBG in cross-sectional analyses. In longitudinal, multivariable analyses, an annualized increase in BMI was inversely related to a concurrent annualized decrease in SHBG (β = -0.79 ng/dl, and SE = 0.22 in Blacks; β = -1.07 ng/dl; and SE = 0.31 in Whites). However, early increases in BMI were not related to later decreases in SHBG. Conclusion: Increases in adiposity are closely tied to decreases in SHBG, but changes in BMI and SHBG may occur concurrently rather than sequentially. Copyright © 2008 by The Endocrine Society.