GLP-1 receptor agonists and sexual function in women and men: a narrative review of emerging evidence and the need for further research.

INTRODUCTION: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) may influence reward-related and sexual behaviors. OBJECTIVE: To synthesize evidence from preclinical and clinical studies evaluating the impact of GLP-1 RAs on libido and sexual function in both women and men. METHODS: A structured synthesis of published studies examining GLP-1 RAs in relation to sexual behaviors, libido, and sexual parameters was performed using PubMed. RESULTS: In animal models, the GLP-1 RA exendin-4 administration suppressed sexual interaction behaviors in a brain region-specific manner, particularly within the laterodorsal tegmental area, posterior ventral tegmental area, and nucleus accumbens shell, while activation of the nucleus of the solitary tract reduced pre-sexual, sexual, and post-sexual behaviors accompanied by elevated corticosterone and altered monoamine turnover. These findings suggest diminishing sexual motivation and performance in rodents through neuroendocrine and stress-related mechanisms. In humans, evidence remains mixed. Pharmacovigilance analyses from the FDA Adverse Event Reporting System revealed reports of erectile dysfunction, decreased libido, and orgasmic dysfunction among GLP-1 RA users, but disproportionality analyses indicated insignificant associations. A social media-based netnographic analysis of user posts found self-reported reductions in substance use and compulsive behaviors, with variable effects on libido-ranging from enhancement attributed to weight loss and improved body image to decreased desire in others. A randomized, double-blind crossover trial in healthy lean men demonstrated that dulaglutide had no effect on sexual desire, hypothalamic-pituitary-gonadal axis hormones, or semen parameters, suggesting no direct impairment of male sexual or reproductive function. However, recent clinical case reports have identified possible female sexual side effects. CONCLUSION: Collectively, preclinical evidence supports inhibitory effects of GLP-1 receptor activation on sexual motivation, whereas human findings are limited and reveal heterogeneous outcomes possibly influenced by gender, metabolic status, GLP-1 RA drug type, and psychosocial factors. Further mechanistic and controlled clinical studies are warranted since there seems to be a divergence between preclinical and clinical data.