The effect of metformin on homocysteine levels in patients with polycystic ovary syndrome: A systematic review and meta‐analysis

Abstract Purpose Metformin is widely used as an insulin sensitizer in polycystic ovary syndrome (PCOS) patients. However, previous studies have found that the effect of metformin on the level of homocysteine were not consistent in PCOS patients. The aim of this review was to analyze the effect of metformin on homocysteine levels in patients with PCOS patients. Methods The Cochrane Library, Pubmed, and Web of Science were searched according to predefined search terms. There is no restriction for publication time and language. Results Eleven studies were included and the data were extracted. The homocysteine level in PCOS patients was significantly increased after taking metformin (mean difference [MD] −1.33; 95% confidence interval [CI] −2.16 to −0.49, p = 0.002). Subgroup analysis showed that the level of homocysteine was generally increased in PCOS patients with body mass index (BMI) ≥25 after taking metformin alone (MD −1.82; 95% CI −2.56 to −1.07, p < 0.00001). There was no significant change in homocysteine level in PCOS patients with BMI <25 (MD 0.69; 95% CI −0.41 to 1.79, p = 0.22). Subgroup analysis showed that there was no significant difference when taking metformin >3 months or taking metformin ≤3 months ( p = 0.84). Taking metformin ≥1700 mg/days significantly increased homocysteine levels in PCOS patients (MD −2.05; 95% CI −2.40 to −1.70, p < 0.00001). When taking metformin <1700 mg/days, there was no significant difference in homocysteine level in PCOS patients (MD 0.15; 95% CI −1.06 to 1.37, p = 0.80). The difference between the two subgroups was significant ( p = 0.0006). There was no significant difference in vitamin B12 level before and after metformin treatment (MD 24.70; 95% CI −22.54 to 71.93, p = 0.31). There was a decrease in serum folic acid level after metformin administration (MD 1.03; 95% CI 0.80 to 1.26, p < 0.00001). Conclusion Taking metformin alone increased homocysteine levels and decreased folic acid levels in nonpregnant PCOS patients. And, it was suggested that the dosage of metformin should be less than 1700 mg/days. The supplement of folic acid and B vitamins during metformin administration may be essential in nonpregnant PCOS patients. We should pay much attention to the potential effect of metformin in PCOS patients.