Effects of vitamin D supplementation in endometriosis: a systematic review

Systematic review and meta-analysis of human clinical trials plus preclinical studies in endometriosis. The human evidence came from randomized trials in women with endometriosis, including surgically confirmed cases and an IVF subgroup; participants were all female, with ages roughly ranging from 12 to 25 years in one trial and about 20 to 35.6 years across studies.

Vitamin D was evaluated as oral supplementation across randomized human endometriosis trials, using regimens that included 50,000 IU weekly for 12 weeks, 2,000 IU daily for 24 weeks, 50,000 IU every 2 weeks for 12 weeks, and a single 600,000 IU oral dose before IVF. The active intervention was vitamin D or vitamin D3 compared with placebo.

Vitamin D supplementation did not show a clear clinical benefit for endometriosis-related pain or IVF outcomes in human randomized trials. For dysmenorrhea, the pooled evidence from 2 studies (44 vitamin D vs 44 placebo) showed no significant effect; for non-cyclic pelvic pain, 2 studies (42 vitamin D vs 38 placebo) also showed no significant effect. Individual trial findings were mixed: one study found no significant improvement in dysmenorrhea (p = 0.45) or pelvic pain (p = 0.24), another reported pain reduction that was not significantly different from placebo (p = 0.97), and the IVF trial found no improvement in clinical pregnancy rate with cumulative pregnancy rate similar to placebo (p = 0.90). Preclinical animal and in vitro studies suggested anti-endometriotic activity, but these findings did not translate into demonstrated human benefit.

The evidence base was small and heterogeneous, with differing vitamin D doses, durations, diagnostic methods, and outcomes across studies. Some endpoints were informed by only one trial, limiting precision, and the review combined human randomized data with preclinical findings that are not directly clinically generalizable. Follow-up was short in the available trials, and baseline vitamin D status varied across studies.