Insights into Vitamin E with Combined Oral Contraceptive on INSR Gene in PCOS by Integrating In Silico and In Vivo Approaches.

Polycystic ovarian syndrome (PCOS) is a hormone disorder common among reproductive-aged women. This is associated with the symptoms like an irregular menstrual cycle, excess androgens, and polycystic ovary. Interestingly, vitamin E acts like the hormone progesterone and improves insulin sensitivity in PCOS. The study aims to evaluate the therapeutic effect of vitamin E in combination with combined oral contraceptive (COC) against PCOS by in silico and in vivo methods. The therapeutic effect of vitamin E (25 and 50mg/kg) in combination with COC (0.4mg/kg) was screened by the in silico method using Auto dock vina 4.2.6. Additionally, in vivo studies with a letrozole-induced PCOS model were performed in 30 female SD rats (n = 6 in each group) for 8 weeks with different doses of vitamin E. Furthermore, histopathological features and the insulin receptor (INSR) gene were scrutinized. An in silico study showed that drospirenone and vitamin E have an excellent affinity to bind to INSR and have higher binding energy (- 8.5 kcal/mol and - 8.7 kcal/mol, respectively). In vivo results showed a significant reduction in elevated testosterone levels compared to that of the PCOS group; follicle-stimulating hormone (FSH) and insulin levels also showed significant changes and reversed anti-oxidant levels in a dose-dependent manner. Ovarian histopathological changes were observed in different follicle counts in addition to the INSR gene, which showed changes in densitometry values. Supplementation of vitamin E combined with COC could be effective against PCOS, and clinical studies must be carried out further.