Acupuncture for premature ovarian insufficiency: a systemic neuroendocrine perspective

Premature ovarian insufficiency (POI) is increasingly viewed not merely as an ovarian-centered reproductive disorder but as a systemic neuroendocrine condition characterized by multilevel dysregulation spanning the central nervous system, ovaries, immune system, metabolism, and stress-response networks. Beyond disruption of the hypothalamic-pituitary-ovarian (HPO) axis, POI involves impairment of the KNDy-GnRH network, chronic inflammatory activation, gut-ovary axis-related metabolic disturbances, and dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis and autonomic nervous system. Acupuncture has been proposed as a multi-target neuroendocrine intervention whose effects may extend beyond local ovarian regulation toward broader physiological modulation. Available evidence suggests that acupuncture may influence reproductive hormone regulation, including follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estradiol (E2), and may be associated with changes in ovarian reserve-related indicators and menstrual function. Some studies also report effects on stress-related endocrine activity, autonomic function, and emotional symptoms, potentially involving inflammatory and metabolic pathways. Experimental evidence further suggests possible effects on hypothalamic neuropeptide signaling, ovarian oxidative stress and inflammation, and systemic stress-metabolic pathways. However, the current evidence is limited by small sample sizes, short follow-up durations, and methodological variability, and there is insufficient evidence regarding clinically meaningful long-term outcomes. Overall, while acupuncture demonstrates biological plausibility and preliminary therapeutic potential, its clinical efficacy in POI remains inconclusive. Further well-designed, large-scale studies incorporating standardized outcome measures and long-term endpoints are required to evaluate its effectiveness and clarify its mechanisms. This review aims to delineate the systemic neuroendocrine mechanisms and potential clinical roles of acupuncture in POI, providing a conceptual framework to guide future research and integrative therapeutic strategies.