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.