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.