Abstract
OBJECTIVE: A small randomized controlled trial suggested that vitamin D might increase the production of testosterone in men, which is supported by experimental studies in animals and a cross-sectional study showing positive associations between plasma 25-hydroxyvitamin D [25(OH)D] and testosterone and concordant seasonal variation of both biomarkers. DESIGN AND MEASUREMENTS: We investigated the cross-sectional association of plasma 25(OH)D levels and total and free testosterone measured by immunoassay in 1362 male participants of the Health Professionals Follow-up Study who were selected for a nested case-control study on prostate cancer using multivariate-adjusted linear and restricted cubic spline regression models. RESULTS: 25(OH)D was positively associated with total and free testosterone levels. From the lowest to the highest 25(OH)D quintile, multivariate-adjusted means (95% confidence interval) were 18·5 (17·7; 19·4), 19·4 (18·6; 20·2), 19·6 (18·8; 20·4), 20·1 (19·3; 20·9) and 20·0 (19·1; 20·8; P-trend = 0·003) for total testosterone and 97·7 (93·9; 101·5), 98·2 (94·1; 102·2), 99·2 (95·2; 103·2), 100·7 (96·9; 104·5) and 101·5 (97·6; 105·4; P-trend = 0·03) for free testosterone. The shapes of the dose-response curves indicate that the association between 25(OH)D and total and free testosterone is linear at lower levels of 25(OH)D (below approximately 75-85 nmol/l), reaching a plateau at higher levels. Unlike for 25(OH)D, we did not observe any seasonal variation of testosterone concentrations. CONCLUSION: This study supports previously reported positive associations between vitamin D and testosterone although we did not observe parallel seasonal variation patterns. Possible causality and direction of the vitamin D-testosterone association deserve further scientific investigation.