The neuroendocrine-appetite-mental health triangle in PMOS: Implications for GLP-1 receptor agonist therapy

Polyendocrine metabolic ovarian syndrome (PMOS) is the most prevalent endocrine disorder in women of reproductive age, yet its management remains fragmented across metabolic, reproductive, and psychological domains. This review uses a descriptive clinical framework-the "neuroendocrine-appetite-mental health triangle"-to organize existing evidence on three interacting pathogenic domains in PMOS: hypothalamic neuroendocrine dysfunction (aberrant GnRH pulsatility, central leptin resistance, and hypothalamic inflammation), appetite dysregulation and disordered eating (binge eating disorder, food addiction, and reward pathway dysfunction), and psychological comorbidities (depression, anxiety, and HPA axis hyperactivity). Within this framework, we evaluate the therapeutic potential of glucagon-like peptide-1 receptor agonists (GLP-1RAs), whose central and peripheral mechanisms may address multiple aspects of this pathology. We synthesize current evidence on their metabolic, reproductive, and emerging psychotropic effects, while providing a balanced and objective assessment of their safety profile, with particular emphasis on the unresolved questions surrounding reproductive safety, the necessity for preconception washout periods, and conflicting signals regarding psychiatric adverse events. We conclude that while GLP-1RAs show therapeutic potential for PMOS, their clinical application requires further evidence, particularly regarding reproductive safety and psychiatric effects, and should be embedded within a multidisciplinary care model that integrates metabolic, psychological, and reproductive management.