Impact of Vitamin D Supplementation on Menstrual Cycle Irregularities among Women with Polycystic Ovary Syndrome who were Treated with Metformin: A Systematic Review with Meta-Analysis

Background: There is inconsistency in the evidence about the effect of adding vitamin D supplements to metformin therapy among women with polycystic ovary syndrome (PCOS). Objective: In this systematic review, we described the differences in menstrual cycle irregularities between women who received vitamin D supplementation and those who didn’t receive vitamin D among women who diagnosed with PCOS and received metformin. Methods: We reviewed previous literature to identify all relevant studies. The included studies' quality and risk of bias were assessed using the Consolidated Standards of Reporting Trials (CONSORT) and the Reporting of Observational Studies in Epidemiology (STROBE) instrument. Cochrane's Q-test and I² statistic were used to assess the heterogeneity across included studies. The fixed-effect model was used to calculate the total effect size. Results: Six studies were included, involving 633 women diagnosed with PCOS. Supplementation of vitamin D with metformin could have a significant impact on the improvement of menstrual cycles compared to receiving metformin alone (OR = 2.11, 95% CI, 1.40- 3.19). There was no evidence of heterogeneity across included studies. Subgroup analysis showed that the magnitude of the association increased when only infertile women with PCOS were included (OR = 2.37, 95% CI, 1.52-3.72). Conclusion: This evidence suggests the possible benefit of adding vitamin D to metformin in regulating the menstrual cycle among women with PCOS, especially infertile women.