Association between serum 25-hydroxyvitamin D and serum sex steroid hormones among men in NHANES

Background: Recent literature suggests that high circulating vitamin D may increase prostate cancer risk. Although the mechanism through which vitamin D may increase risk is unknown, vitamin D concentration could influence circulating sex steroid hormones that may be associated with prostate cancer; an alternate explanation is that it could be associated with prostate-specific antigen (PSA) concentration causing detection bias. Objective: We examined whether serum vitamin D concentration was associated with sex steroid hormone and PSA concentrations in a cross-sectional analysis of men in the National Health and Nutrition Examination Surveys (NHANES). Design: Testosterone, oestradiol, sex hormone-binding globulin (SHBG), androstanediol glucuronide, and 25-hydroxyvitamin D (25(OH)D) were measured in serum from men aged 20 and older participating in NHANES III (n = 1315) and NHANES 2001–2004 (n = 318). Hormone concentrations were compared across 25(OH)D quintiles, adjusting for age, race/ethnicity, body fat percentage, and smoking. PSA concentration was estimated by 25(OH)D quintile in 4013 men from NHANES 2001–2006. Results: In NHANES III, higher testosterone (quintile (Q) 1 = 17·2, 95% confidence interval (CI) = 16·1–18·6; Q5 = 19·6, 95% CI = 18·7–20·6 nmol/l, P-trend = 0·0002) and SHBG (Q1 = 33·8, 95% CI = 30·8–37·0; Q5 = 38·4, 95% CI = 35·8–41·2 nmol/l, P-trend = 0·0005) were observed with increasing 25(OH)D. Similar results were observed in NHANES 2001–2004. PSA concentration was not associated with serum 25(OH)D (P-trend = 0·34). Conclusion: Results from these nationally representative studies support a positive association between serum 25(OH)D and testosterone and SHBG. The findings support an indirect mechanism through which vitamin D may increase prostate cancer risk, and suggest the link to prostate cancer is not due to PSA-detection bias.