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.