Metabolic Dysregulation in Polycystic Ovary Syndrome: The Central Role of Insulin Resistance and Novel Therapeutic Perspectives
DOI:
https://doi.org/10.56127/jukeke.v5i1.2415Keywords:
Polycystic Ovary Syndrome, Insulin Resistance, Hyperinsulinemia, Metabolic Dysfunction, Mitochondrial Dysfunction, Personalized TherapyAbstract
Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder with complex reproductive and metabolic consequences that remain insufficiently addressed by symptom-oriented management strategies. This study aims to review and synthesize recent evidence on the metabolic basis of PCOS, emphasizing the importance of insulin resistance and hyperinsulinemia as central mechanisms underlying both metabolic and reproductive abnormalities. A narrative review method was employed by analyzing peer-reviewed literature published in recent years, focusing on studies examining insulin signaling disturbances, mitochondrial dysfunction, oxidative stress, inflammatory pathways, and emerging therapeutic approaches in PCOS. The main findings indicate that insulin resistance and hyperinsulinemia act as key drivers of PCOS across diverse phenotypes, including non-obese women, while mitochondrial dysfunction and chronic inflammation further amplify metabolic–reproductive impairment. The results also show that improvements in metabolic parameters do not consistently align with normalization of reproductive hormones, underscoring the heterogeneous and multifactorial nature of PCOS. These findings have important implications for clinical practice, supporting the adoption of personalized, mechanism-based management strategies that integrate metabolic profiling with reproductive goals. The originality of this review lies in its integrative metabolic–reproductive framework, which consolidates emerging mechanistic insights and novel therapeutic perspectives to reconceptualize PCOS as a systemic metabolic–reproductive disorder.
References
Balkrishna, A., Rana, M., Mishra, S., Agrawal, R., Rajput, S. K., Dhanasekaran, M., Arya, V., Ramu, R., Upadhayay, A., & Singh, S. (2025). Exploring the therapeutic potential of phytochemicals apigenin and ellagic acid in managing polycystic ovarian syndrome and its comorbidities: A comprehensive review. Frontiers in Endocrinology, 16. https://doi.org/10.3389/fendo.2025.1633377
Deng, H., Chen, Y., Xing, J., Zhang, N., & Xu, L. (2024). Systematic low-grade chronic inflammation and intrinsic mechanisms in polycystic ovary syndrome. Frontiers in Immunology, 15. https://doi.org/10.3389/fimmu.2024.1470283
Dutta, S., Sengupta, P., Rao, S., Elgarawany, G. E., Samrot, A. V, Rosas, I. M., & Roychoudhury, S. (2025). Targeting polycystic ovary syndrome (PCOS) pathophysiology with flavonoids: From adipokine–cytokine crosstalk to insulin resistance and reproductive dysfunctions. Pharmaceuticals, 18(10). https://doi.org/10.3390/ph18101575
Dzienny, A. C., & Seifer, D. B. (2025). Impact of reducing obesity in PCOS: Methods and treatment outcomes. Journal of Personalized Medicine, 15(11). https://doi.org/10.3390/jpm15110518
Gkantzos, A., Kalogiannis, S., & Deda, O. (2025). The role of aromatic amino acids in polycystic ovary syndrome through patients’ blood metabolic profiling: A systematic review of the past five years. Journal of Proteome Research, 24(5), 2208–2221. https://doi.org/10.1021/acs.jproteome.4c00867
Houston, E. J., & Templeman, N. M. (2025). Reappraising the relationship between hyperinsulinemia and insulin resistance in PCOS. Journal of Endocrinology, 265. https://doi.org/10.1530/JOE-24-0269
Li, J., Qiao, J., Li, Y., Qin, G., Xu, Y., Lao, K., Wang, Y., Fan, Y., Tang, P., & Han, L. (2025). Metabolic disorders in polycystic ovary syndrome: From gut microbiota biodiversity to clinical intervention. Frontiers in Endocrinology, 16. https://doi.org/10.3389/fendo.2025.1526468
Mahoney, A., & D’Angelo, A. (2025). Treatment options for managing anovulation in women with PCOS: An extensive literature review of evidence-based recommendations for future directions. Life, 15(6). https://doi.org/10.3390/life15060863
Pluta, D., Migacz, M., Kochman, K., Krajewski, B., Holecki, M., & Madej, P. (2025). Polycystic ovary syndrome patients with metabolic dysfunction-associated steatotic liver disease—Comparison of the diagnostic methods. Endokrynologia Polska, 76(2), 145–152. https://doi.org/10.5603/EP.a2025.0018
Saadati, S., Mason, T., Godini, R., Vanky, E., Teede, H., & Mousa, A. (2025). Metformin use in women with polycystic ovary syndrome (PCOS): Opportunities, benefits, and clinical challenges. Diabetes, Obesity and Metabolism, 27(S3), 31–47. https://doi.org/10.1111/dom.15132
Saeed, A. A. M., Noreen, S., Awlqadr, F. H., Farooq, M. I., Qadeer, M., Rai, N., Farag, H. A., & Saeed, M. N. (2025). Nutritional and herbal interventions for polycystic ovary syndrome (PCOS): A comprehensive review of dietary approaches, macronutrient impact, and herbal medicine in management. Journal of Health, Population and Nutrition, 44. https://doi.org/10.1186/s41043-025-00437-9
Tharayil, S. P., & Shukla, P. (2025). Connecting the dots: Mitochondrial dysfunction, PCOS, and insulin resistance—Insights and therapeutic advances. International Journal of Molecular Sciences, 26(13). https://doi.org/10.3390/ijms26136233
Wang, R., Qi, S., Wang, Q., Lang, J., Pang, C., & Wang, K. (2025). Hydroxychloroquine enhances insulin sensitivity and ameliorates abnormal lipid metabolism in obese women with polycystic ovary syndrome. BMC Endocrine Disorders, 25. https://doi.org/10.1186/s12902-025-01408-9
Zhang, Q., Yang, Z., Ou, X., Zhang, M., Qin, X., & Wu, G. (2025). The role of immunity in insulin resistance in patients with polycystic ovary syndrome. Frontiers in Endocrinology, 15. https://doi.org/10.3389/fendo.2024.1464561
