Causal Link Between Vitamin D and Total Testosterone in Men: A Mendelian Randomization Analysis

Area of Science:

• Endocrinology
• Nutritional Science
• Genetics

Background:

• Low circulating vitamin D levels are epidemiologically associated with reduced total testosterone.
• Vitamin D deficiency is prevalent and correctable, making this association potentially significant for public health.

Purpose of the Study:

• To investigate the causal relationship between genetically determined vitamin D levels and total testosterone using Mendelian randomization.
• To assess if lower vitamin D influences total testosterone levels.

Main Methods:

• Employed Mendelian randomization (MR) methodology.
• Utilized data from 4254 men in the SPECT-China study.
• Constructed a genetic risk score (GRS) using four single-nucleotide polymorphisms associated with 25-hydroxyvitamin D [25(OH)D] levels as an instrumental variable.

Main Results:

• Multivariable analysis showed an association between lower 25(OH)D and lower total T (β = 0.40).
• The vitamin D GRS (VD_GRS) was significantly associated with both 25(OH)D and total T.
• MR analysis indicated a causal effect: a per-standard deviation increase in genetically determined 25(OH)D was associated with a 0.12 increase in total T (95% CI, 0.02 to 0.22).

Conclusions:

• The study provides evidence supporting a biologically plausible causal effect of 25-hydroxyvitamin D on total testosterone.
• Further long-term randomized controlled trials are warranted to determine if vitamin D supplementation can increase androgen levels.