Beyond metabolism: sexual dysfunction and weight-loss drugs

Abstract Introduction Sexual dysfunction (SD) is a frequent and underrecognized complication of obesity, mediated by a complex interplay of hormonal, vascular, metabolic, and psychosocial pathways. Despite the established link between weight reduction and improved sexual health, the specific effects of new pharmacological weight-loss therapies on sexual function remain underexplored. Objectives To critically evaluate the recent evidence on the impact of weight-loss medications on sexual function, synthesizing clinical outcomes, mechanistic insights, and identifying critical research gaps. Methods We conducted an update and comprehensive narrative review using PubMed, Scopus and Embase databases. A systematic search strategy employed predefined terms related to obesity, SD, and pharmacotherapy. Eligible studies were those reporting sexual outcomes using validated instruments [eg, Female Sexual Function Index (FSFI), International Index of Erectile Function (IIEF)] or relevant clinical reports. Results GLP-1 receptor agonists show promising results in men, improving erectile function, testosterone levels, and sperm parameters. In contrast, direct evidence in women remains limited. Tirzepatide achieves unprecedented weight loss, but case reports suggest potential sexual side effects. Naltrexone/bupropion may benefit sexual desire through mood improvement, while phentermine/topiramate primarily enhances psychological well-being. Setmelanotide demonstrates the direct involvement of the melanocortin pathway in sexual function. Across all drug classes, sexual endpoints were typically secondary outcomes in clinical trials. Conclusion Pharmacological weight-loss therapies influence sexual health through multiple direct and indirect pathways. However, current evidence is inconsistent, and sex-specific data are scarce. Future clinical trials should systematically include validated sexual function measures as primary endpoints and stratify results by sex and comorbidities to better guide clinical practice in sexual medicine.