Empagliflozin as a potential therapy for PCOS: Restoring hormonal balance and ovarian function in a letrozole-induced rat model.

Abstract

BACKGROUND: Polycystic ovarian syndrome (PCOS) is a prevalent endocrine disorder that often leads to infertility. The characteristic hyperandrogenemia and elevated luteinizing hormone /follicle stimulating hormone ratio, resulting in ovulation failure, are the hallmarks of PCOS. Recent preclinical and clinical studies revealed the potential of empagliflozin (EMPA; a sodium-glucose cotransporter-2 inhibitor) to improve PCOS symptoms. However, the effects of EMPA on endocrine disturbances and ovarian cyst formation were not thoroughly investigated. OBJECTIVES: The primary objective of this study was to explore the potential of EMPA as a treatment for PCOS. METHODS: PCOS was induced by daily administration of letrozole (1 mg/kg for 21 days). The PCOS group was then divided into PCOS (untreated), PCOS+EMPA (10 mg/kg), and PCOS + metformin (300 mg/kg). All groups, except for the vehicle-treated group, continued to receive letrozole throughout the 21-day treatment period. Serum and ovaries were collected for various measurements at the end of the experiments. RESULTS: The results of the study showed that induction of PCOS resulted in high testosterone levels, luteinizing hormone /follicle stimulating hormone ratio, and ovarian weights. Disturbed apoptosis and high transforming growth factor-β and inducible nitric oxide synthase expression were also evident in the PCOS group. EMPA treatment resulted in an ameliorative effect of these changes, comparable to metformin's effect. CONCLUSION: Our results suggest that EMPA could be a promising treatment for PCOS in rats, with its protective effect potentially mediated through its ability to restore hormonal imbalance and to restore transforming growth factor-β and inducible nitric oxide synthase expression, providing reassurance to the audience about its efficacy.