A systematic review of vitamin D and endometriosis: role in pathophysiology, diagnosis, treatment, and prevention

Objective: To assess the current literature evaluating the role of vitamin D in endometriosis in humans. Evidence Review: A systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines within PubMed, Embase, the Cochrane Library, the Web of Science, and Scopus. A comprehensive search strategy was developed by a data informationist. Observational and interventional studies assessing endometriosis and vitamin D association in humans published in English up to March 10, 2022, were included. Two reviewers independently screened studies evaluating the role of vitamin D in endometriosis. The risk of bias was assessed using the Cochrane Risk of Bias 2.0 tool, Newcastle-Ottawa scale, and Strengthening the Reporting of Observational Studies in Epidemiology. Extracted data were analyzed descriptively. Results: Of 1,921 studies identified, 29 met the eligibility criteria after screening the titles, abstracts, and full texts and were included in this systematic review. Of these, 13 were clinical studies, 12 were preclinical studies, and 4 had components of both preclinical and clinical studies. Eight of the 11 clinical studies evaluating the vitamin D levels reported that low vitamin D levels were associated with endometriosis, whereas a study found higher vitamin D levels in endometriosis, and the rest did not report an association. Experimental studies found that vitamin D played an important role in multiple pathogenetic processes, such as cell proliferation, invasion, degradation, and inflammation, by regulation of cytokines, including interleukin-6 and interleukin-8, prostaglandin activity, and matrix metalloproteinases. The expressions of important genes, such as EGFR, MDGF, PDGFB, 1α-OHase, and CYP24A1, involved in the development of endometriosis were found to be influenced by vitamin D. Only 1 of 9 studies evaluating the polymorphism of the vitamin D receptor gene found an association of endometriosis with the BsmI variant of the VDR gene. Two studies reported the diagnostic accuracy of the urinary vitamin D binding protein as an isolated biomarker of endometriosis to be limited. Clinical trials studying the efficacy of vitamin D in treating the symptoms of endometriosis were equivocal. Conclusion: Data were strongly supportive of a correlation between low vitamin D levels and endometriosis in most studies. Studies suggesting the role of vitamin D in the regulation of important cellular and signaling pathways involving gene expressions and cytokines in endometriosis have been consistent. Further studies evaluating the therapeutic efficacy of vitamin D in endometriosis are required because the data were equivocal. Data regarding increased dietary intake of vitamin D as a preventive measure have been promising; however, evidence was limited, and thus, further research is needed.