Association of endogenous sex hormone levels with coronary artery calcium progression among post-menopausal women in the Multi-Ethnic Study of Atherosclerosis (MESA)

Background: Sex differences in the incidence and manifestation of cardiovascular disease (CVD) suggest the involvement of sex hormones in disease pathogenesis. Coronary artery calcium (CAC) and its progression, measured by non-contrast cardiac computed tomography, are markers of subclinical atherosclerosis and predict CVD, even among low-risk women. We hypothesized that sex hormone levels were associated with CAC progression among women in the Multi-Ethnic Study of Atherosclerosis. Methods: We studied 2759 post-menopausal women (age 65 ± 9 years), free of baseline CVD, with baseline serum sex hormones and CAC measured at Exam 1 (2000–2002). Of this sample, 2427 had ≥1 follow-up CAC measurement through Exam 5 (2010–2012). Using mixed effects linear regression methods, we tested change in log[CAC+1] score by log[sex hormone] levels (continuous, comparing the 90th versus 10th percentiles). Models adjusted for demographics, lifestyle factors, cardiovascular risk factors, hormone therapy, and years since menopause. Results: At baseline, we found no associations between sex hormones and prevalent CAC. Over a median of 4.7 years, in fully-adjusted models, women with higher free testosterone levels had relatively greater CAC progression [Ratio 1.26 (95% CI 1.01–1.56)], whereas higher sex hormone binding globulin (SHBG) was associated with lower progression risk [0.80 (0.64–0.99). No associations were seen for total testosterone, estradiol, or dehydroepiandrosterone. Conclusion: A more androgenic hormone profile of higher free testosterone and lower SHBG is associated with a greater CAC progression up to 10-years in post-menopausal women. Sex hormone levels may help identify women at increased risk for CVD who may benefit from additional risk-reducing strategies.