Effects of vitamin D supplementation on metabolic and endocrine parameters in PCOS: a randomized-controlled trial

Premenopausal women with PCOS, aged ≥18 years, with 25(OH)D < 75 nmol/L; single-center, double-blind, randomized, placebo-controlled trial; 180 participants randomized in a 2:1 ratio to vitamin D vs placebo; conducted at the Medical University of Graz, Austria (Dec 2011 - Jul 2017).

Vitamin D3 (cholecalciferol) 20,000 IU weekly for 24 weeks, taken orally as 50 oil drops per week.

Primary outcome: no significant difference in AUCgluc after 24 weeks between vitamin D and placebo (mean treatment effect −9.19; 95% CI −21.40 to 3.02; p = 0.139). Vitamin D supplementation increased 25(OH)D by 33.4 nmol/L (95% CI 24.5–42.2; p < 0.001), reduced PTH, and increased 1,25(OH)2D. A 60-minute OGTT plasma glucose decrease of 10.2 mg/dL (95% CI −20.2 to −0.3; p = 0.045) was observed. Other metabolic and endocrine parameters showed no significant changes; menstrual frequency did not improve significantly. In a predefined subgroup with baseline 25(OH)D < 50 nmol/L (n=60), AUCgluc decreased after 24 weeks by 19.20 (95% CI −35.45 to −2.95; p = 0.021); this subgroup finding is post hoc and exploratory. Safety: no hypercalcemia or serious adverse events.

Relatively high dropout rate; single-center design; participants had relatively high baseline 25(OH)D, limiting generalizability to more deficient populations; multiple testing across eight glucose-related outcomes increases risk of type I error; post hoc subgroup analyses (baseline 25(OH)D < 50 nmol/L) are underpowered and exploratory.