THE IMPACT OF NEUROENDOCRINE, GENETIC, AND ENVIRONMENTAL FACTORS ON THE PATHOPHYSIOLOGY OF POLYCYSTIC OVARY SYNDROME AND FEMALE FERTILITY: A COMPREHENSIVE REVIEW OF HORMONAL REGULATION AND CLINICAL IMPLICATIONS
Abstract
Polycystic ovary syndrome (PCOS) represents one of the most prevalent endocrine disorders among women of reproductive age, exerting significant effects on fertility, metabolic homeostasis, and overall health. The syndrome arises from complex interactions among hormonal, genetic, and environmental factors that disrupt the hypothalamic-pituitary-ovarian (HPO) axis. Neuroendocrine dysregulation, characterized by increased pulsatility of gonadotropin-releasing hormone (GnRH) and an elevated luteinizing hormone (LH) to follicle-stimulating hormone (FSH) ratio, promotes excessive ovarian androgen production and follicular arrest. Hyperandrogenism, insulin resistance, and chronic anovulation form the core pathophysiological triad of PCOS. Genetic studies (GWAS) have identified loci associated with gonadotropin regulation, steroidogenesis, and insulin signaling, while environmental exposures, including endocrine-disrupting chemicals (EDCs), may act as epigenetic triggers in genetically susceptible individuals. Epidemiological analyses demonstrate a steady global increase in PCOS incidence, with the highest prevalence in high-income regions. Clinical heterogeneity is reflected by four Rotterdam phenotypes, differing in metabolic and reproductive consequences. PCOS not only impairs natural fertility but also affects assisted reproductive outcomes by altering oocyte quality and ovarian responsiveness. Comprehensive understanding of hormonal and metabolic disturbances is essential for individualized diagnosis and therapy. Future research should focus on elucidating epigenetic mechanisms and optimizing targeted treatments to improve fertility and reduce long-term metabolic risks in affected women.
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