The efficacy and safety of metformin combined with simvastatin in the treatment of polycystic ovary syndrome: A meta-analysis and systematic review

Background:Several previous randomized controlled trials (RCTs) evaluated the efficacy of metformin combined with simvastatin in the treatment of polycystic ovary syndrome (PCOS), yet the results of the researches are not consistent. It is necessary to conduct a meta-analysis to explore the efficacy and safety of metformin combined with simvastatin in the treatment of PCOS, to provide evidence supports for the treatment of PCOS.Methods:We searched PubMed, EMbase, Cochrane Library, China National Knowledge Infrastructure, Wanfang, and Chinese biomedical literature databases online to identify the RCTs evaluating the efficacy of metformin combined with simvastatin in the treatment of PCOS. Standardized mean difference (SMD) and 95% confidence interval (95% CI) were calculated to evaluate the synthesized effects.Results:Nine RCTs with a total of 746 PCOS patients were included. The synthesized results indicated that the combined use of metformin and simvastatin are more beneficial to reduce the total cholesterol (SMD –2.66, 95% CI –3.65 to –1.66), triglycerides (SMD –1.25, 95% CI –2.02 to –0.49), low density lipoprotein (SMD –2.91, 95% CI –3.98 to –1.84), testosterone (SMD –0.64, 95% CI –1.13 to –0.15), fasting insulin (SMD –1.17, 95% CI –2.09 to –0.26) than metformin alone treatment in PCOS patients (all P < .001), and there was no significant difference in the high density lipoprotein (SMD –0.05, 95% CI –0.56–0.46), luteinizing hormone (SMD –0.58, 95% CI –1.66 to –0.50), follicle stimulating hormone (SMD 0.41, 95% CI –0.78–1.59), prolactin (SMD –1.38, 95% CI –2.93–0.17), fasting blood sugar (SMD 0.23, 95% CI –0.52–0.97), and insulin sensitivity index (SMD –0.17, 95% CI –0.48–0.15) between experimental and control groups (all P > .05).Conclusions:Metformin combined with simvastatin is superior to metformin alone in the treatment of PCOS patients with more advantages in improving the levels of sex hormones, blood lipids, and blood sugar. However, the safety of this therapy still needs to be further explored in clinical studies with high-quality and large samples.