Treatment with metformin and combination of the metformin plus pioglitazone on serumlevels of IL-6 and IL-8 in polycystic ovary syndrome: A randomized, clinical trial

Statement of the Problem: Elevated serum levels of inflammatory mediators reflect low-grade chronic inflammation and have been attributed to be associated with insulin-resistant states. Therefore, insulin-lowering agents have been recommended to improve both reproductive and metabolic aspects of PCOS. This study aimed to compare metformin and combination of metformin plus pioglitazone on menstrual cyclicity, hormonal parameters, insulin resistance and inflammatory biomarkers in women with PCOS. Methodology & Theoretical Orientation: One hundred and six women with PCOS participated in the study. All subjects were randomized in to two-arm interventions. Arm-1: metformin 500 mg (BD) daily. Arm-2: Combined (metformin 500 mg BD and pioglitazone 15 mg BD) for 12 weeks. The primary outcome measure was serum level of IL-6 and IL-8 using ELISA assay. Secondary outcome was insulin resistance; assessed using HOMA-IR. Findings: At baseline women with PCOS had significantly elevated circulating concentrations of IL-6 and IL-8. Treatment decreased IL-6 in both groups, however only the combination group (p= 0.005) had a significant decrease. IL-8 had a significant decrease after treatment in both groups (p= <0.001). HOMA-IR and insulin levels also decreased in both groups (both p= <0.001). Testosterone, FSH and prolactin significantly decreased in both groups. LH also decreased in both groups, however, the change was significant only in the combination group (p=0.013). Both treatment groups were associated with the reduction in menstrual irregularities, sizes of ovaries and number of follicles. Significance: Combination of metformin and pioglitazone therapy was more effective compared to metformin alone in reducing the levels of IL-6 and IL-8 as well as insulin resistance in PCOS. The addition of pioglitazone with metformin had an additional effect on decreasing inflammation and normalizing hormonal imbalance. Thus modified treatment protocols of combination therapy could further improve the outcome.