Effects of vitamin D supplementation during weight loss on sex hormones in postmenopausal women

Objective: The aim of the study was to compare the effects of vitamin D3 supplementation versus placebo on serum sex hormones in postmenopausal women completing a 12-month diet + exercise weight loss program. Methods: Two hundred eighteen overweight or obese women (50-75 y) with serum 25-hydroxyvitamin D at least 10 to less than 32 ng/mL (insufficient) were randomized to either weight loss + 2,000 IU/day oral vitamin D-3, or to weight loss + daily placebo. Serum sex hormone-binding globulin, estrone, total, free, and bioavailable estradiol, and testosterone were measured by radioimmunoassay before randomization and at 12 months. Mean changes were compared between groups (intent-to-treat) using generalized estimating equations. Results: The 12-month changes in sex hormone-binding globulin, estrone, total, free, and bioavailable estradiol, and testosterone did not differ between groups (all P > 0.05). However, a greater increase in serum 25-hydroxyvitamin D was associated with a greater increase in sex hormone-binding globulin (P-trend = 0.01), and larger decreases in free and bioavailable estradiol (P-trend = 0.04, P-trend = 0.03, respectively). In post-hoc analyses, we compared women randomized to vitamin D whose serum 25-hydroxyvitamin D remained insufficient (n = 38), to women who became replete (25-hydroxyvitamin D >= 32 ng/mL; n = 53). Replete women showed greater reductions in bioavailable estradiol (-1.8 vs -0.7 pg/mL), free testosterone (-0.8 vs -0.3 pg/mL), and bioavailable testosterone (-1.8 vs -0.6 ng/dL), and a greater increase in sex hormone-binding globulin (10.6 vs 4.7 nmol/L) (all P < 0.05), even after adjusting for differences in total 12-month weight loss. Conclusions: Overall, 12-month changes in sex hormone did not differ between groups. However, vitamin D repletion was associated with greater reductions in sex hormones during weight loss, with a possible dose-dependent effect. Future studies should test higher doses and target circulating 25-hydroxyvitamin D levels when measuring such effects.