Anorgasmia following initiation of GLP-1 agonist

Abstract Introduction According to the Obesity Medicine Association, obesity is a chronic, progressive, relapsing, multifactorial and treatable neurobehavioral disease. A small number of drugs have been approved by the Food & Drug Administration (FDA) for weight loss. Liraglutide, Tirzepatide, and Semaglutide are GLP-1 agonists and anti-diabetic drugs, and are some of the latest FDA-approved medications for weight loss. Up to 50% of patients experience gastrointestinal (GI) distress, a common side effect, while taking these medications. Other side effects include tachycardia, antibody-mediated angioedema, anaphylaxis, irritation at the injection site, and hypoglycemia. However, very little is known regarding sexual dysfunction as a side effect of GLP-1 agonists. The following case report discusses the potential negative impact on sexual function of these widely prescribed anti-diabetic, weight loss medications. The case report also discusses a proposed mechanism of action of GLP-1 agonists on sexual function. Aims To report the sexual side effects and plausible mechanism of female anorgasmia from GLP-1 agonists. Methods Chart review of the patient case was conducted. Consultation with a Doctor of Pharmacy was also requested for additional guidance on possible mechanisms of action of GLP-1 agonists on sexual function. Results Several proposed mechanisms causing anorgasmia were theorized, the most likely being GLP-1 agonist vasoconstriction of smooth muscle, which results in reduced oxygen delivery and blood flow to the genitals. This may hinder genital engorgement and arousal, in addition to causing impairment of smooth muscle contractions essential for orgasms. Other mechanisms of GLP-1 agonist-induced anorgasmia may involve their signaling in the brain due to their presence in the hypothalamus. GLP-1 receptor modulation in the hypothalamus may decrease dopamine and norepinephrine signaling, which are neurotransmitters crucial for motivation, pleasure, and orgasm as well as disrupt pathways involved in sexual desire and arousal. Conclusion Further investigation on the prevalence of sexual dysfunction with GLP-1 agonists and their mechanism of action is needed.