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J Clin Endocrinol Metab. 2019 Mar 21. pii: jc.2018-01874. doi: 10.1210/jc.2018-01874. [Epub ahead of print]

Causal link between vitamin D and total testosterone in men: A mendelian randomization analysis.

Author information

1
Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China.

Abstract

CONTEXT:

Low circulating vitamin D levels have been associated with lower total testosterone. These epidemiological associations, if true, would have public health importance, since vitamin D deficiency is common and correctable. We aimed to test whether genetically lowered vitamin D levels were associated with lower total testosterone (T), using Mendelian randomization (MR) methodology.

DESIGN AND SETTING:

4,254 men were enrolled from the SPECT-China study, which was performed in 23 sites in East China during 2014 to 2016. Using four single-nucleotide polymorphisms (SNPs) strongly associated with 25-hydroxyvitamin D (25(OH)D) levels, we created a genetic risk score (GRS) as instrumental variable (IV) to estimate the effect of genetically lowered 25(OH)D on total T.

MAIN OUTCOME MEASURE:

Total T was detected by chemiluminescenceassay.

RESULTS:

Lower measured 25(OH)D levels were associated with lower total T (B 0.40, 95%CI 0.23, 0.58) after multivariable adjustment. In addition, per SD increase in the VD_GRS was significantly associated with 25(OH)D (B -1.64, 95%CI -2.04, -1.24) and with total T (B -0.19, 95%CI -0.37, -0.02). Using VD_GRS as IV in the MR analysis, the causal regression coefficient (βIV) of genetically determined per SD increase for 25(OH)D on total T was 0.12 (95%CI 0.02, 0.22).

CONCLUSIONS:

The study provided evidence for the biologically plausible causal effects of 25(OH)D on total T using MR analysis. Whether vitamin D supplementation can raise androgen levels merits further investigation in long-term randomized controlled trials.

PMID:
30896763
DOI:
10.1210/jc.2018-01874

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