Therapeutic Frameworks for Neuroendocrine and Metabolic Reversal in PCOS: A Narrative Review of the Gut–Brain–Ovary Axis

Abstract

Polycystic Ovary Syndrome (PCOS) is a complex neuroendocrine and metabolic disorder, rather than just an ovarian condition. Standard treatments often fail to fully resolve persistent issues such as inflammation, infertility, metabolic dysfunction, obesity and mood disorders. This review explores a novel therapeutic synergy: Combining vagus nerve stimulation (VNS) with gut microbiome manipulation to target the pathobiology of PCOS. A comprehensive literature search across major databases (including PubMed, Scopus and Google Scholar) analysed studies from January 2010 to May 2026. The search focused on autonomic dysfunction, gut dysbiosis, inflammation, neuroendocrine reproductive control, vagus nerve physiology and systems biology approaches to metabolic and gynaecological health. Synthesising these findings yielded a novel framework: Concurrently modulating the gut microbiota and vagus nerve activity can synergistically restore neuroendocrine, immune and metabolic homeostasis in PCOS patients. Co-targeting the gut–brain axis using noninvasive transcutaneous VNS alongside personalised microbiome interventions offers a promising direction for precision medicine. This combined strategy could significantly advance future PCOS management.