Synergistic therapeutic effects of metformin and curcumin on polycystic ovary syndrome via regulation of insulin resistance and oxidative stress in a rat model.

OBJECTIVE: Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disorder characterized by insulin resistance, hyperandrogenism, and elevated oxidative stress. The present study aimed to investigate the synergistic therapeutic effects of metformin and curcumin on insulin resistance and oxidative stress in a rat model of PCOS. MATERIALS AND METHODS: Thirty female Sprague-Dawley rats were randomly assigned to blank control (n = 6) and experimental (PCOS) groups (n = 24). The PCOS model was induced through daily subcutaneous injections of dehydroepiandrosterone (DHEA, 60 mg/kg) for 20 days. Subsequently, the experimental group was subdivided into four groups: PCOS-only, PCOS-metformin (300 mg/kg), PCOS-curcumin (50 mg/kg), and PCOS-metformin-curcumin (combined treatment). Treatments were administered daily via oral gavage for another 20 days. Estrous cycles, ovarian morphology, serum sex hormones, insulin resistance, and oxidative stress in ovarian tissues were assessed. RESULTS: Combined treatment with metformin and curcumin significantly restored estrous cyclicity, improved ovarian morphology, reduced serum testosterone and luteinizing hormone levels, decreased LH/FSH ratio, and ameliorated insulin resistance compared to monotherapy groups. Moreover, the combined treatment markedly decreased ovarian oxidative stress markers (ROS and MDA) and enhanced antioxidant enzyme activities (GPx, SOD, GSH), surpassing the effects of either agent alone. CONCLUSION: Combined administration of metformin and curcumin demonstrated synergistic therapeutic effects in PCOS rats by concurrently addressing insulin resistance and oxidative stress. These findings support the clinical potential of this combination as an effective strategy for managing PCOS. Further clinical studies are necessary to validate these promising preclinical findings.