(825) Emerging Effects of Glucagon-Like Peptide-1 Receptor Agonists and Sodium-Glucose Cotransporter 2 Inhibitors on Male Sexual Hormones and Behaviors

Abstract Introduction The use of glucagon-like peptide-1 receptor agonists (GLP1-RA) and sodium-glucose cotransporter 2 inhibitors (SGLT2i) resulted in weight loss and long-term cardiovascular (CV) and renal preserving safety. Their role in male sexual hormone and behavior is still not sufficiently investigated. Objective To review and meta-analyze the effects of GLP1-RA and SGLT2i on obesity-associated hypogonadism and sexual dysfunctions Methods Publications from January 1, 1969, up to January 31st, 2025 were included. In addition, to better analyze the impact of GLP1-RA or SGLT2i on hormonal and sexual parameters, data obtained with the latter search were used for a meta-analytic approach. Results Eight studies evaluated the effects of GLP-1-RA on the HPT axis. Overall, 367 subjects with a mean age of 42.7±10.6 years, a mean BMI of 33.5±5.1 kg/m2, and a mean follow-up of 29.0±20.4 weeks were included in the analysis. Three studies investigated the role of glifozines on several parameters, including T and sexual function. Overall, 52 subjects with a mean age of 47.2±14.1 years, a mean BMI of 31.7±2.5 kg/m2, and a mean follow-up of 22.7±25-7 weeks were analyzed. Either GLP1-RA or SGLT2i resulted in an improvement of body composition and metabolic profile supporting erectile function amelioration. Only GLP1-RA showed an increase in total and calculated free testosterone without affecting gonadotropin levels, while for SGLT2i, the data are contradictory. The finding on GLP1-RA was independent of the observed weight loss, suggesting a direct rather than an indirect mechanism of action on the hypothalamus pituitary testis axis. Finally, the use of testosterone replacement therapy showed better results as compared to GLP1-RA when orgasm and sexual satisfaction domains were investigated. Conclusions Considering the beneficial effects of GLP1-RA on long-term CV mortality and morbidity, compared to the substantially neutral effects derived from the use of TRT, we support the use of this class of medications for improving sexual dysfunction and its underlying CV problems in overweight and obese patients with ED. Disclosure No