Vitamin D supplementation and circulating testosterone levels in breast cancer survivors: insights from a multicentric randomized study

Vitamin D plays a key role in immune modulation, cell proliferation, and hormone regulation while testosterone levels may contribute to breast cancer (BC) progression when dysregulated. This study aimed at evaluating whether long-term oral vitamin D3 supplementation affects serum testosterone levels in BC survivors. Data were derived from 253 women with early-stage BC participating in DEDiCa trial and randomized to receive either a high-dose vitamin D3 to maintain serum 25(OH)D at 60 ng/mL (group A) or a standard dose to maintain serum levels at 30 ng/mL (group B). Serum 25(OH)D, testosterone, and sex hormone binding globulin (SHBG) were assessed at baseline, 12 and 24 months. While serum 25(OH)D significantly increased in both groups (p<0.001), no clinically meaningful changes in testosterone concentrations were observed between treatment groups (group A: 0.169±0.14 to 0.195±0.170 ng/mL; group B: 0.191±0.163 to 0.205±0.141 ng/mL, for baseline and 24-months respectively; p=0.683). A slight increase was observed in group A at 24 months but remained within physiological ranges. Baseline testosterone levels were the strongest predictor of hormonal variation (p<0.001). This analysis does not support a clinically significant change in serum testosterone concentrations by oral cholecalciferol D3 supplementation despite a two-year high-dose oral treatment within an active lifestyle trial.维生素D在免疫调节、细胞增殖及激素调控中发挥关键作用，而睾酮水平失调时可能促进乳腺癌（Breast Cancer，BC）的进展。本研究旨在评估长期口服维生素D3补充剂是否会影响乳腺癌幸存者的血清睾酮水平。研究数据来自参与DEDiCa试验的253名早期乳腺癌女性受试者，她们被随机分配至两组：A组接受大剂量维生素D3，以维持血清25-羟维生素D（25-hydroxyvitamin D，25(OH)D）水平至60 ng/mL；B组接受标准剂量维生素D3，以维持血清25(OH)D水平至30 ng/mL。研究在基线、12个月及24个月时检测了受试者的血清25-羟维生素D、睾酮及性激素结合球蛋白（Sex Hormone Binding Globulin，SHBG）水平。尽管两组受试者的血清25-羟维生素D水平均显著升高（p<0.001），但不同干预组间的睾酮浓度未出现具有临床意义的变化：A组基线至24个月时睾酮浓度从0.169±0.14 ng/mL升至0.195±0.170 ng/mL，B组从0.191±0.163 ng/mL升至0.205±0.141 ng/mL，组间比较p=0.683。A组在24个月时睾酮水平出现轻微升高，但仍处于生理正常范围内。基线睾酮水平是激素水平变化的最强预测因子（p<0.001）。本研究分析结果显示，尽管在这项针对活跃生活方式人群的试验中进行了为期两年的大剂量口服干预，口服胆钙化醇（维生素D3）补充剂并未使血清睾酮浓度出现具有临床意义的显著变化。