Evaluation of ovarian and metabolic effects of GnRH modulators in two rat models of polycystic ovary syndrome.

Gonadotropin-releasing hormone (GnRH) modulators are widely used in numerous reproductive conditions including infertility. Several clinical studies showed mixed results regarding the efficacy of GnRH modulators in patients with polycystic ovary syndrome (PCOS). Along with this, few preclinical studies focus on the effect of GnRH modulators in PCOS-induced animals. Therefore, the present study was designed to study the effect of leuprolide and cetrorelix on hormonal, metabolic, and menstrual dysfunction PCOS rats. Prepubertal female rats were divided into four groups: Group I received a normal pellet diet and Groups II, III, and IV received 40% high-fat diet for 105 days. Similarly, adult female rats were divided into four groups: Group I received 1% carboxymethylcellulose (CMC) and Groups II, III, and IV received letrozole (1 mg/kg, per oral [p.o.] in 1% CMC) for 21 days. Thereafter, leuprolide (2.5 µg/rat, s.c.) and cetrorelix (10 µg/kg, subcutaneous [s.c.]) treatment were given to Group III and Group IV animals, respectively, for 21 days. Oral glucose tolerance test, lipid profile, fasting glucose, insulin, estrus cycle, hormonal profile, ovary weight, ovarian histopathological changes, and LHR and FSHR expressions were measured. Treatment with leuprolide and cetrorelix did not improve glucose intolerance, insulin level, insulin sensitivity indices, sex hormone levels, lipid profile, and estrus cycle. Only testosterone level, total cholesterol level, and follicular development were improved. Therefore, it was concluded that both leuprolide and cetrorelix showed improvement in follicular development, which could be helpful for improving fertility in PCOS.