Vitamin D Deficiency Is Associated with Increased Uterine Fibroid Risk: A Systematic Review and Meta-Analysis

Uterine fibroids, the most common benign tumors in women of reproductive age, are the leading cause for hysterectomies and disproportionately affect African American women. This is an updated systematic review that performs a novel meta-analysis of observational studies to quantify the association between serum vitamin D levels and uterine fibroids across a wide range of studies. Additionally, a comprehensive review is included on vitamin D-related factors in both preclinical and clinical studies to assess vitamin D's efficacy in treatment and prevention. Cochrane Library, Embase, PubMed, Scopus, and Web of Science were searched for publications from inception to April 2024. Risk of bias was assessed using Cochrane RoB 2.0 and the Newcastle-Ottawa Scale. Statistical analysis was conducted using R software and the use of a random effects model with restricted maximum-likelihood estimated the overall effect. Sixty-nine studies met the inclusion criteria and were categorized as preclinical (n=26) or clinical (n=43). One preclinical study explored downregulation of vitamin D receptors as a mechanism for pathogenesis; others reported a link between vitamin D-related polymorphisms and increased risk of fibroids. Twenty-nine clinical studies evaluated hypovitaminosis D and fibroid prevalence; twenty-six confirmed an association, while three found no significant differences. Analysis of 21 clinical studies found a large negative effect size (Mean Difference = -5.90ng/mL; I² = 97.4%; p < 0.001), indicating that women with fibroids had markedly lower vitamin D levels compared to controls. Supplementation was shown to improve fibroid-associated symptoms in nine clinical interventional studies, with some demonstrating a reduction in fibroid size and others showing prevention in fibroid progression. The data supports a promising role for vitamin D supplementation in regulating fibroids and highlights the need for further clinical investigation of vitamin D as a potential alternative therapy. PROSPERO REGISTRATION: CRD420261320154, 20 Feb 2026.