Vitamin D3 Supplementation

Béla E Tóth et al. (2025) · Nutrients

This prospective, double-blind, two-phase randomized controlled trial with 84 analyzed participants explored whether weekly high-dose vitamin D3 (a fat-soluble vitamin that also acts on hormone-producing tissue through its receptor, VDR) could improve ovarian function in polycystic ovary syndrome (PCOS), a common hormonal condition marked by irregular or absent ovulation (the release of an egg), elevated androgens ("male-pattern" hormones such as testosterone), and, frequently, vitamin D deficiency. Earlier studies had linked low vitamin D status to PCOS but disagreed on whether raising vitamin D levels actually changes ovulation, cycle length, or hormone levels. Conducted at eight Hungarian clinical sites between 2016 and 2020, the trial randomized women meeting Rotterdam PCOS criteria to one of two oral regimens: 30,000 IU of vitamin D3 weekly, plus calcium, either immediately for 24 continuous weeks or only after a 12-week placebo lead-in period. Ovarian morphology was tracked with transvaginal ultrasound, and ovulation was confirmed through luteal-phase progesterone testing (values above 10 ng/mL) rather than self-report alone, at baseline and after 12 and 24 weeks of treatment. After 12 weeks of vitamin D3, average menstrual cycle length dropped by 11.7 days (p = 0.032, meaning this reduction was unlikely to be due to chance), and confirmed ovulation rose from about 40% to 59-65% of participants (p = 0.044). Serum vitamin D rose to a mean of 45.1 ng/mL (p < 0.001), confirming adequate repletion. Testosterone fell significantly only in two specific subgroups: women with elevated androstenedione ("hyperandrogenic," p = 0.047) and those with a higher LH/FSH hormone ratio (p = 0.0082) — a pattern the authors connect to differing PCOS phenotypes rather than one uniform hormonal response. Ultrasound-confirmed normal ovarian appearance was reached in 20% of participants after 12 weeks (p < 0.05 versus placebo), improving further by 24 weeks, though that later difference was not statistically significant. No serious treatment-related side effects were reported, and vitamin D levels stayed within the study's predefined safety range throughout. The authors suggest vitamin D3 could serve as a standalone or add-on approach for PCOS, particularly for hyperandrogenic phenotypes and those with a higher LH/FSH ratio. They identify the trial's sample size (84 analyzed participants), the relatively short 12-plus-12-week duration, and luteal-phase-only hormone sampling as limitations restricting broader conclusions, and note that longer trials with serial ultrasound monitoring and larger, phenotype-defined groups are needed to confirm these phenotype-specific patterns and to establish how long the ovulatory and cycle-length benefits persist after treatment ends.