Effect of Metformin and Flutamide on Insulin, Lipogenic and Androgen-Estrogen Signaling and Cardiometabolic Risk in a PCOS-prone Rodent Model.

Polycystic Ovary Syndrome (PCOS) is a highly associated with cardiometabolic risk and the metabolic syndrome (MetS), predisposing women to increased risk of developing Type 2 Diabetes and Cardiovascular Disease (CVD). Metformin is commonly used to treat insulin resistance-glucose intolerance, and flutamide, an androgen receptor antagonist, is used to target hyperandrogenemia and dyslipidemia. Currently, the physiological mechanism of action of these treatments on androgen, lipidogenic and insulin signaling pathways remains unclear in the PCOS. The aim of this study was to investigate the effect and mechanism of action of metformin and flutamide on plasma lipid-ApoB-lipoprotein and insulin-glucose metabolism and endocrine-reproductive indices in a PCOS-prone MetS rodent model. PCOS-prone rodents were treated with metformin (300 mg/kg body wt), flutamide (30 mg/kg body wt) or metformin-flutamide for 6 weeks. Metformin was shown to improve fasting insulin and HOMA-IR, whereas flutamide and combination treatm...