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Mokhlarbegim

 

Mokhlarbegim

Republican Specialized Scientific and Practical Medical Center of Endocrinology, Uzbekistan

Abstract Title:

Obesity as a Biological Amplifier of Genetic Risk in Polycystic Ovary Syndrome: Metabolic Consequences and Personalized Approaches

Research Interests:

Introduction. Polycystic ovary syndrome (PCOS) and obesity frequently co-occur, creating a particularly severe clinical phenotype with far-reaching reproductive and metabolic consequences. Depending on the population and diagnostic criteria used, overweight or obesity is observed in 40–70% of women with PCOS [1, 2]. This combination is not coincidental but rather reflects profound pathophysiological interactions in which obesity acts as a biological amplifier of genetically determined abnormalities. Understanding the mechanisms by which excess adiposity exacerbates the PCOS phenotype and how genetic variants modulate these effects is essential for developing personalized treatment strategies [3, 4]. Objective. To analyze the role of obesity as a modifying factor in PCOS, to characterize the gene-obesity interactions that determine the severity of the metabolic phenotype, and to outline personalized therapeutic approaches based on genetic profiling. Materials and Methods. A systematic analysis of scientific literature published between 2000 and 2025 was performed using PubMed, Scopus, and Web of Science databases. Search terms included PCOS, obesity, overweight, insulin resistance, gene-environment interaction, FTO, PPARG, LEPR, metabolic syndrome, and personalized medicine. The review incorporates findings from cohort studies, randomized controlled trials, meta-analyses, and pharmacogenetic studies. Conclusion. PCOS and obesity represent mutually reinforcing pathological states. Obesity not only exacerbates the metabolic and reproductive features of PCOS but also amplifies the effects of genetic variants that predispose to insulin resistance and hyperandrogenism. The severity of the metabolic phenotype in PCOS with obesity is substantially modified by individual genetic makeup, particularly variants in FTO, PPARG, LEPR, and INSR. Genotype-informed personalized approaches — including intensified lifestyle modification, early use of insulin sensitizers, and targeted pharmacotherapy with GLP-1 receptor agonists or thiazolidinediones — have the potential to improve treatment outcomes and reduce long-term morbidity in this high-risk population. Further research is needed to validate genotype-guided algorithms in prospective clinical trials and to assess their cost-effectiveness in routine practice.