Circulating sex steroids and vascular calcification in community-dwelling men: The Framingham Heart Study

Context: The relationship between sex steroids and atherosclerosis is poorly understood. Objective: To describe the association of serum total T (TT), calculated free T (cFT), estrone (E1), estradiol (E2), and SHBG to vascular calcification in adult men. Design: Observational study (Framingham Heart Study). Analyses are cross-sectional. TT, E1, and E2 were measured by liquid chromatography-tandem mass spectrometry, and SHBG by immunofluorometric assay. Estimates of association were obtained by Tobit regression, which acknowledges the influence of floor effects on outcomes. Setting: General community. Participants: A total of 1654 community-dwelling men from the Offspring and Third Generation cohorts of the Framingham Heart Study. Main Outcome Measures: Coronary artery calcification (CAC), abdominal aortic calcification, and thoracic aortic calcification were measured by computed tomography. Results: Mean (standard deviation [SD]) age was 49 (10) years. Mean (SD) TT, cFT, and SHBG were: 616 (224) ng/dL, 111 (45) pg/mL, and 46 (23) nmol/L, respectively. Mean (SD) E2 and E1 were 28 (10) and 39 (14) pg/mL. Vascular calcification at all sites was negatively associated with TT and cFT and positively associated with E2 and E1. A 100-ng/dL between-subjects increase in TT was associated with a mean (95% confidence interval) age-adjusted difference in CAC of -23% (-41%, -4%) (P = .02). After model adjustment for other cardiovascular risk factors, the estimated associations between T and vascular calcification scores were statistically nonsignificant. Conclusions: Decreased circulating T and E2 levels are associated with an age-adjusted increase in CAC, but these associations appear to express relationships either attributable to or mediated by established cardiovascular risk factors.