Effects of metformin treatment on serum levels of C-reactive protein and interleukin-6 in women with polycystic ovary syndrome

Abstract

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 (I2 = 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 (I2 = 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.

The Effects of Metformin, Ethinyl Estradiol/Cyproterone Acetate, and Metformin Ethinyl Estradiol/Cyproterone Acetate Combination Therapy on Carotid Artery Intima-media Thickness in Patients with Polycystic Ovary Syndrome

“…The majority of the studies in PCOS have shown increased levels of CRP (19,25). In a meta-analysis, it was found that increased CRP levels decreased in patients with PCOS after metformin treatment (25). In our study, we found that CRP level was significantly higher in patients with PCOS compared to the control group.…”

“…The majority of the studies in PCOS have shown increased levels of CRP (19,25). In a meta-analysis, it was found that increased CRP levels decreased in patients with PCOS after metformin treatment (25).…”

Letrozole for patients with polycystic ovary syndrome

“…Various managements were proposed for infertile women with PCOS. [ 18 – 20 ] However, the optimal management option has not been addressed satisfied. Although multiple treatments including weight reduction, clomiphene citrate, metformin, gonadotropins, and ovary cauterization have been reported to treat such condition, the efficacy still has insufficient evidence to support.…”

Network Pharmacology-based Strategy for Predicting Active Ingredients and Potential Targets of Coptis Chinensis Franch in Polycystic Ovary Syndrome

“…Once the MAPK pathway is blocked, mitotic cyclin D2 expression and the role of granulocyte proliferation will be impeded, resulting in a decrease in the number of granulocytes, which indirectly interferes with the development and maturation of follicles [19,20]. Experiments have con rmed that the high expression of IL-6 in PCOS may play a role in the pathogenesis of PCOS through the synergistic effect of insulin resistance and chronic in ammation [21]. The abnormally low expression of the FOS gene in granular cells may increase the androgen secretion of ovarian granular cells by reducing the inhibitory effect on the CYP17 gene [22].…”