Effects of metformin treatment on serum levels of C-reactive protein and interleukin-6 in women with polycystic ovary syndrome: a meta-analysis: A PRISMA-compliant article

BACKGROUND: Metformin is effective for the treatment of polycystic ovary syndrome (PCOS), but conflicting results regarding its impact on serum levels of C-reactive protein (CRP) and interleukin-6 (IL-6) in women with PCOS have been reported. To provide high-quality evidence about the effect of treatment with metformin on CRP and IL-6 in PCOS, relevant studies that assessed the serum levels of CRP and IL-6 in women with PCOS receiving metformin treatment were reviewed and analyzed. METHODS: A literature search was conducted in the Science Citation Index, PubMed, Embase, and Cochrane Library databases, and personal contact was made with the authors. Random-effects model was used to estimate the standardized mean differences (SMDs) with 95% confidence intervals (95% CIs). To ensure synthesis of the best available evidence, subgroup analysis, sensitivity analysis, meta-regression analysis, and publication bias were performed. RESULTS: Of 216 studies identified, 20 were included in the meta-analysis (7 prospective, nonrandomized studies, and 13 randomized control trials). Data suggest that serum levels of CRP were decreased after metformin treatment in PCOS patients with an SMD (95% CI) of −0.86 [−1.24 to −0.48] and P = .000 (random-effects). However, significant heterogeneity was detected across studies (I(2) = 84.6% and P = .000). Unfortunately, the sources of heterogeneity were not found by subgroup analysis and meta-regression analysis. Serum IL-6 concentrations were not significantly changed after metformin treatment in PCOS with an SMD (95% CI) of −0.48 [−1.26 to 0.31] and P > .05 (random-effects). Significant heterogeneity was also detected across studies (I(2) = 90.9% and P = .000). The subgroup analysis suggested that treatment-related reductions in serum IL-6 levels were significantly correlated with BMI, whereas the sources of heterogeneity were not found. In addition, we noticed that metformin treatment could decrease BMI in the CRP and IL-6 related studies (SMD = −0.45, 95% CI: −0.68 to −0.23; SMD = −0.44, 95% CI: −0.73 to −0.16). CONCLUSION: This meta-analysis showed a significant decrease of serum CRP levels, especially in obese women, but no significant changes in IL-6 levels after metformin treatment in women with PCOS. In general, the data support that early metformin therapy may ameliorate the state of chronic inflammation in women with PCOS. Considering the obvious heterogeneity reported in the literature, further well-designed investigations with larger samples are needed to ascertain the long-term effects of metformin on chronic inflammation in PCOS.