The Association of Vitamin D with Uterine Fibroids in Premenopausal Patients: A Systematic Review and Meta-Analysis

Objective: This study aims to consolidate existing literature regarding the association between vitamin D and uterine fibroid presence and growth. Data sources: A comprehensive search across databases including Medline, Embase, CINAHL, Web of Science, ClinicalTrials.gov, and grey literature was conducted from inception to February 2023, using relevant keywords. Authors were contacted for unpublished data. Study selection: From 9931 studies screened based on title and abstract, those evaluating serum vitamin D levels or vitamin D treatment effects, using ultrasonography for diagnosis, and involving at least 25 premenopausal participants were included. Case reports, case series, and reviews were excluded. Data extraction and synthesis: Data were extracted using a predefined form. Methodological quality was assessed through the Newcastle-Ottawa Scale and the Risk of Bias-2 tools. Evidence quality was evaluated using Grading of Recommendations Assessment, Development, and Evaluation. Data from 3 randomised controlled trials (n = 328) and 23 observational studies (n = 5650) were meta-analyzed via random-effects modelling. Patients receiving oral vitamin D supplementation had a significantly different change in fibroid size (standardized mean difference-5.7%; CI-10.63 to-0.76, P = 0.02, I-2 = 99%), as measured by the percentage change in diameter or volume, compared to controls, over the span of 2-6 months. Those receiving supplementation had vitamin D insufficiency; regimens varied between 50 000 IU weekly for 12 weeks, 50 000 IU weekly for 8 weeks, and 50 000 IU biweekly for 10 weeks. Patients with fibroids exhibited lower serum vitamin D concentrations (mean difference-5.50 ng/mL; CI 6.99 to-4.01, P < 0.001, I-2 = 87%) and higher odds of vitamin D deficiency (OR 3.71; CI 1.90-7.24, P <0.001, I-2 = 80%). Conclusion: This review underscores the potential of vitamin D in mitigating fibroid development and growth. While promising, further research is warranted to optimise dosage and treatment duration, potentially offering a non-invasive solution for at-risk patients. Continued exploration of vitamin D's role in fibroid treatment is encouraged.