Genetically Determined Low Vitamin D Concentrations Associated With Low Testosterone Levels

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PCR analysis
Genetically low 25-hydroxyvitamin D levels are associated with lower testosterone levels.

Genetically low 25-hydroxyvitamin D (25[OH]D) levels are associated with lower testosterone levels, according to study results published in The Journal of Clinical Endocrinology & Metabolism. According to the researchers, data from the study, which focused on people of Chinese descent, support possible causal effects of 25(OH)D on total testosterone levels.

Many previous studies have reported the effect of vitamin D deficiency on various extraskeletal disorders. Observational and cross-sectional studies have linked vitamin D deficiency with lower testosterone levels. There are conflicting results regarding the possible effect of vitamin D supplementation on testosterone levels.

In this mendelian randomization study, the researchers investigated the association between genetically low 25(OH)D concentrations and low testosterone levels. They used data from an ongoing SPECT-China (Survey on Prevalence in East China for metabolic diseases and risk factors) study, a large cross-sectional study of adult Chinese citizens, including 4254 men with available genotype information.

Vitamin D genetic risk score was constructed based on 4 single-nucleotide polymorphisms, chosen on the basis of a recent genome-wide association study of 25(OH)D, as they were strongly associated with 25(OH)D levels. This risk score was used to estimate the effect of genetically low 25(OH)D levels on total testosterone levels.

Not surprisingly, with increasing vitamin D genetic risk score, there was an increase in serum 25(OH)D levels. The data showed an association between lower serum 25(OH)D levels and lower total testosterone (β=0.40; 95% CI, 0.23-0.58) following multivariable adjustment. Furthermore, vitamin D genetic risk score was negatively and significantly associated with total testosterone levels (β=-0.19; 95% CI, -0.37 to -0.02) after multivariable adjustment.

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Formal mendelian randomization using instrumental variable (genetic risk score) was used to examine the causal effect of 25(OH) D on total testosterone. In this analysis, the causal regression coefficient of genetically determined 25(OH)D for total testosterone was 0.12 (95% CI, 0.02-0.22).

The researchers acknowledged that the study had several limitations, including focusing solely on participants of Asian descent and creating a vitamin D genetic risk score based only on the basis common variants.

“Our study demonstrated that a genetic decrease in 25(OH)D was associated with lower [testosterone], providing evidence in support of a causal role of vitamin D in raising [testosterone],” concluded the investigators, who called for further prospective studies to confirm this relationship.

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Chen C, Zhai H, Cheng J, et al. Causal link between vitamin D and total testosterone in men: a mendelian randomization analysis [published online March 21, 2019]. J Clin Endocrinol Metab. doi:10.1210/jc.2018-01874