Improvement of oral contraceptive-induced glucose dysregulation and dyslipidemia by valproic acid is independent of circulating corticosterone

Context: Cardiometabolic disorders are rapidly becoming major public health challenges. Valproic acid (VPA) is a widely prescribed anticonvulsant drug. Objective: We hypothesized that treatment with VPA would improve the regulation of glucose and atherogenic dyslipidemia through reduction in circulating corticosterone. Methods: Female Wistar rats recieved (p.o.) combined oral contraceptive (COC) containing 1.0 µg ethinylestradiol plus 5.0 µg levonorgestrel and valproic acid (VPA; 20 mg) for 8 weeks. Results: Treatment with COC led to elevated fasting blood glucose, insulin, corticosterone, triglycerides (TG), TG/HDL-cholesterol ratio, insulin resistance (IR) and impaired glucose tolerance. VPA significantly attenuated the alterations induced by COC treatment, but did not affect the corticosterone level. However, VPA treatment led to significant increases in plasma insulin, corticosterone, atherogenic lipids and impaired glucose tolerance in rats not treated with COC. Conclusion: The findings in this study suggest that VPA mitigates against the development of COC-induced insulin resistance and dyslipidemia independent of elevated circulating corticosterone.