GABA Dysfunction and Its Consequences in Women with Polycystic Ovary Syndrome

Background and Objective: The GABA system plays an important role in the development, maturation, and function of gonadotropin-releasing hormone (GnRH)-secreting neurons, as well as in the coordination of reproductive and metabolic signals. Considering the emerging evidence in this area, dysfunction of the GABA system may be involved in the development of polycystic ovary syndrome (PCOS). The aim of this study is to summarize the available evidence on dysfunction of the GABA system and its implications for women with PCOS. Methods: This systematic review was conducted using the keywords Gamma-Aminobutyric Acid (GABA), GABAergic pathway, PCOS and their related MeSH and searching for English articles from 2000 to 2023 in WOS, Embase, Scopus and PubMed databases. Articles that conducted clinical research on the relationship between GABA supplementation or the GABA pathway and PCOS were identified as relevant articles. The quality of the studies was assessed using the Newcastle-Ottawa tool. Findings: A total of 260 articles were found in the initial search, of which only 7 were selected. There is evidence that GABA and PCOS are associated, but the causal direction and underlying mechanism are unclear. Some studies have shown that PCOS alters the levels or function of GABA in the blood or brain, leading to psychological and physiological consequences. On the other hand, GABA dysfunction affects amino acid metabolism and GnRH hormone signaling, helping to improve PCOS symptoms. Conclusion: Based on the results of this study, GABA may play an important role in the pathophysiology of PCOS by regulating GnRH neurons and GABA inputs to them. GABA is also a signaling molecule in various tissues and organs outside the brain, and GABA pathways may affect GnRH neuron function and PCOS development through different mechanisms.