Association between High Serum Homocysteine Levels and Biochemical Characteristics in Women with Polycystic Ovarian Syndrome: A Systematic Review and Meta-Analysis

BACKGROUND: Elevated homocysteine levels have been observed in previous studies of PCOS; however, the nature of the associations between high homocysteine levels and the biochemical characteristics of polycystic ovarian syndrome (PCOS)—such as obesity, insulin resistance (IR), and androgen levels—is still uncertain. METHODS: A systematic search was conducted electronically up to December 28, 2015 using specific eligibility criteria. Standardized mean difference (SMD) and the corresponding 95% confidence intervals (95% CIs) were used as a measure of effect size. RESULTS: A total of 34 studies (with 1,718 cases and 1,399 controls) of homocysteine levels in PCOS were pooled in this meta-analysis. Significantly lower homocysteine levels were found in controls than in PCOS patients (SMD = 0.895, 95% CI = 0.643–1.146, P<0.001; I(2) = 90.4% and P<0.001 for heterogeneity), regardless of the degree of obesity, IR, or androgen levels. Homocysteine levels in non-IR PCOS patients were significantly lower than those of PCOS patients with IR (SMD = 0.69, 95% CI = 0.37–1.01, P<0.01; I(2) = 0% and P = 0.50 for heterogeneity). However, metformin treatment did not appear to cause any significant change in the homocysteine levels of PCOS patients (SMD = –0.17, 95% CI = –1.10–0.75, P = 0.71; I(2) = 92% and P<0.01 for heterogeneity). CONCLUSIONS: High homocysteine levels in women with PCOS are not related to degree of obesity, IR, or androgen levels. Metformin treatment cannot decrease the homocysteine levels in PCOS patients.