Clinical review of how glucagon-like peptide-1 agonist obesity medications decrease sexual desire, and a biopsychosocial model for why we don't 'see' it.

Background: While prevailing assumptions suggest that improved body image and erectile function, even in people with diabetes, associated with glucagon-like peptide-1 (GLP-1) agonist medications would correlate with heightened sexual function, there is limited literature on the effects of GLP-1 agonists on hedonistic pleasures such as sexual activity. In this paper, we aim to elucidate the potential implications of GLP-1 agonists on sexual desire by proposing a serotonergic mechanism by which GLP-1 agonists theoretically decrease sexual desire, and a biopsychosocial perspective on why this effect may be camouflaged by competing influences. Methods: This was a narrative review analysis with target literature search. A PubMed search was conducted to identify systematic reviews or meta-analyses investigating the effects of GLP-1 agonists on physiological and lifestyle factors. We used the same methodology to investigate the connection between GLP-1 agonism and the brain's reward pathways to elucidate whether a connection exists between GLP-1 agonism and sexual desire. Results: We established a theoretical model for how GLP-1 agonist modulation via increased serotonergic activity at the 5-HT2C receptor may result in diminished sexual desire. We then applied a biopsychosocial framework to highlight why this effect may be overlooked by GLP-1-treated patients and clinicians. Although the serotonergic pathway may create a physiological decrease in sexual desire for patients taking GLP-1 agonists, we postulate that this diminishing influence of GLP-1 agonism is both compounded by factors such as undesirable side effects and increased SHBG and offset by the enhancing influences on sexual desire such as increased total testosterone, and improved vascular reactivity and mood. Conclusion: Failing to systematically measure and report on sexual desire as a potential adverse outcome of GLP-1 agonist use overlooks an essential aspect of patient well-being. Future research should prioritize longitudinal studies to assess changes in sexual desire among individuals prescribed GLP-1 agonists.