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Background: Cardiovascular disease (CVD) is the leading cause of death in women. Sex differences in risk factors, prevalence and mortality suggest the involvement of sex hormones in disease processes. Coronary artery calcium (CAC) is a marker of subclinical atherosclerosis and its progression. CAC is prognostic of CVD risk, independent of traditional risk factors, even among low-risk women. We hypothesized that a more androgenic hormone pattern will predict CAC progression over 10 years in post-menopausal women.Methods: We studied 2759 post-menopausal women, aged 45-84 years, participating in MESA who underwent serum sex hormone measurement and a cardiac CT scan for CAC at baseline (2000-2002). Among these, 2427 women had up to 3 follow-up cardiac CT scans at subsequent visits spanning 10 years. CAC was assessed by Agatson units. CAC and sex hormones were log-transformed for analysis. Using multivariable-adjusted Poisson and linear mixed effects models, we tested the longitudinal associations of testosterone (T), free T, dehydroepiandrosterone (DHEA), estradiol (E2), and sex hormone binding globulin (SHBG) with prevalent CAC and progression of CAC over 10 years.Results: At baseline, average age was 65 years, 46% had prevalent CAC and 32% were using hormone therapy (HT). Cross-sectionally, there were no associations between sex hormones and prevalent CAC. After adjustment for demographics, lifestyle factors and use of HT, higher levels of free T and lower levels of SHBG were associated with an increase in CAC progression over 10 years (Table, Model 2). These associations remained statistically significant after adjusting for potential mediating cardiovascular risk factors (Model 3) and in sensitivity analyses excluding women on HT.Conclusion: A more androgenic hormone profile of higher free T and lower SHBG is associated with a greater CAC progression over 10 years in post-menopausal women. Sex hormone levels may help identify women at increased CVD risk who may benefit from other risk reduction strategies.