Katharina Nimptsch; Elizabeth A. Platz; Walter C. Willett; Edward Giovannucci
Clin Endocrinol. 2012;77(1):106-112. © 2012 Blackwell Publishing
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.
Data from a small randomized controlled trial suggest that vitamin D supplementation might increase the production of testosterone in men. In that trial, 54 healthy men whose mean 25(OH)D levels were in the deficiency range (mean 29·7 nmol/l in the placebo group and 32·5 nmol/l in the vitamin D group; to convert nmol/l to ng/ml, divide by 2·5) received either 83 ?g vitamin D daily for 1 year (n = 31) or placebo (n = 23). Compared with baseline values, a significant increase in total testosterone levels (from 10·7 ± 3·9 to 13·4 ± 4·7 nmol/l; P < 0·001) was observed in the vitamin D supplementation group. Similar increases were observed for free testosterone and bioactive testosterone. No changes in testosterone concentrations were observed in the placebo group. In a cross-sectional study among 2299 men who were routinely referred for coronary angiography, positive associations between 25-hydroxy vitamin D [25(OH)D] and total testosterone levels were observed. In the same study, 25(OH)D and total testosterone followed a similar seasonal pattern. A recently published cross-sectional study among 3369 healthy European men observed weak positive associations between 25(OH)D and testosterone levels and an inverse association between 25(OH)D and oestradiol. While these studies suggest a link between 25(OH)D and sex steroids, more studies are warranted, and especially the shape of the dose–response relationship has not been explored so far. There is biological support for a possible association between vitamin D and male reproductive hormones. The vitamin D receptor (VDR) and vitamin D metabolizing enzymes are widely expressed, including in the male reproductive tract. Furthermore, vitamin D levels have been associated with sperm count and motility, and VDR knockout mice have significant gonadal insufficiency, decreased sperm count and motility. The aim of this study was to cross-sectionally investigate the association between vitamin D status as reflected by 25(OH)D concentrations and plasma testosterone and oestradiol in participants of the Health Professionals Follow-up Study (HPFS).
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