Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People's Hospital, Shanghai University School of Medicine, Shanghai, China.
J Clin Endocrinol Metab. 2019 Aug 1;104(8):3148-3156. doi: 10.1210/jc.2018-01874.
Low circulating vitamin D levels have been associated with lower total testosterone levels. These epidemiological associations, if true, would have public health importance because vitamin D deficiency is common and correctable. We tested whether genetically lowered vitamin D levels were associated with lower total testosterone (T), using Mendelian randomization (MR) methodology.
A total of 4254 men were enrolled from the Survey on Prevalence in East China for Metabolic Diseases and Risk Factors (SPECT-China) study, which was performed at 23 sites in eastern China during 2014 to 2016. Using four single-nucleotide polymorphisms strongly associated with 25-hydroxyvitamin D [25(OH)D] levels, we created a genetic risk score (GRS) as an instrumental variable to estimate the effect of genetically lowered 25(OH)D on total T.
Total T was detected by chemiluminescence assay.
Lower 25(OH)D levels were associated with lower total T (β, 0.40; 95% CI, 0.23 to 0.58) after multivariable adjustment. Per-SD increase in the vitamin D GRS (VD_GRS) was significantly associated with 25(OH)D (β, -1.64; 95% CI, -2.04 to -1.24) and with total T (β, -0.19; 95% CI, -0.37 to -0.02). Using VD_GRS as the instrumental variable in the MR analysis, the causal regression coefficient of genetically determined per-SD increase for 25(OH)D on total T was 0.12 (95% CI, 0.02 to 0.22).
We provide 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.
低循环维生素 D 水平与总睾酮水平降低有关。如果这些流行病学关联是真实的，将具有重要的公共卫生意义，因为维生素 D 缺乏是常见且可纠正的。我们使用孟德尔随机化 (MR) 方法来检验基因降低的维生素 D 水平是否与总睾酮 (T) 降低有关。
共有 4254 名男性参加了 2014 年至 2016 年在中国东部 23 个地点进行的代谢性疾病和危险因素普查研究 (SPECT-China)，该研究采用化学发光法检测总 T。使用与 25-羟维生素 D [25(OH)D] 水平密切相关的 4 个单核苷酸多态性，我们创建了一个遗传风险评分 (GRS) 作为工具变量，以估计基因降低 25(OH)D 对总 T 的影响。
采用化学发光法检测总 T。
在多变量调整后，较低的 25(OH)D 水平与总 T 降低相关（β，0.40；95%CI，0.23 至 0.58）。维生素 D GRS（VD_GRS）每增加一个标准差与 25(OH)D 显著相关（β，-1.64；95%CI，-2.04 至-1.24）和总 T（β，-0.19；95%CI，-0.37 至-0.02）。在 MR 分析中，使用 VD_GRS 作为工具变量，基因决定的每增加一个标准差的 25(OH)D 对总 T 的因果回归系数为 0.12（95%CI，0.02 至 0.22）。
我们使用 MR 分析为 25(OH)D 对总 T 的生物学上合理的因果效应提供了证据。维生素 D 补充是否能提高雄激素水平值得在长期随机对照试验中进一步研究。
