The Role of Glp-1 Receptor Agonists in Insulin Resistance with Concomitant Obesity Treatment in Polycystic Ovary Syndrome |
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Authors: | Krzysztof Bednarz,Karolina Kowalczyk,Marlena Cwynar,Dominika Czapla,Wiktor Czarkowski,Dominika Kmita,Artur Nowak,Paweł Madej |
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Affiliation: | 1.Department of Gynecological Endocrinology, Medical University of Silesia in Katowice, 40-752 Katowice, Poland; (K.B.); (M.C.); (D.C.); (W.C.); (D.K.); (P.M.);2.Gynecological and Obstetrician Polyclinic, District Hospital, 15-435 Białystok, Poland; |
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Abstract: | Insulin resistance is documented in clamp studies in 75% of women with polycystic ovary syndrome (PCOS). Although it is not included in the diagnostic criteria of PCOS, there is a crucial role of this metabolic impairment, which along with hormonal abnormalities, increase each other in a vicious circle of PCOS pathogenesis. Insulin resistance in this group of patients results from defects at the molecular level, including impaired insulin receptor-related signaling pathways enhanced by obesity and its features: Excess visceral fat, chronic inflammation, and reactive oxygen species. While lifestyle intervention has a first-line role in the prevention and management of excess weight in PCOS, the role of anti-obesity pharmacological agents in achieving and maintaining weight loss is being increasingly recognized. Glucagon-like peptide-1 receptor agonists (GLP1-RAs) not only act by reducing body weight but also can affect the mechanisms involved in insulin resistance, like an increasing expression of glucose transporters in insulin-dependent tissues, decreasing inflammation, reducing oxidative stress, and modulating lipid metabolism. They also tend to improve fertility either by increasing LH surge in hypothalamus-pituitary inhibition due to estrogen excess connected with obesity or decreasing too high LH levels accompanying hyperinsulinemia. GLP1-RAs seem promising for effective treatment of obese PCOS patients, acting on one of the primary causes of PCOS at the molecular level. |
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Keywords: | polycystic ovary syndrome (PCOS) insulin resistance (IR) glucagon-like peptide-1 receptor agonists (GLP-1RAs) obesity inflammation oxidative stress lipid metabolism infertility |
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