16 • Probe •Vol LXII • No. 4 • Sep–Dec 2023 Insulin Resistance and the Pathogenesis of Polycystic Ovary Syndrome Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders, globally affecting more than 20% of women in their reproductive age. PCOS is a heterogeneous condition characterized by hyperandrogenism, polycystic ovary morphology, and dysfunctional ovulation. Scientific data confirm that most women with PCOS are metabolically resistant to insulin. More than 65% of women with PCOS have insulin resistance (IR) and compensatory hyperinsulinemia. IR has been identified in all 4 phenotypes of PCOS— type A: a combination of polycystic ovary (PCO), chronic oligo-anovulation (OA), and hyperandrogenism (HA); type B: a combination of OA and HA; type C: a combination of PCO and HA; and type D: a combination of PCO and OA. IR is predominantly identified in the classical phenotypes (types A and B) of PCOS (80%). IR—an impaired insulin response in skeletal muscle, hepatic, and adipose tissues—is predominantly due to a defective glucose transport system (glucose transporter type 4) across the plasma membrane. In PCOS, IR occurs due to a disruption in downstream signal transmission from the insulin receptor—a postreceptor abnormality. Thus, women with PCOS exhibit a pronounced unresponsiveness and insensitivity to insulin stimulation in tissues. Bidirectionality Between IR and PCOS In PCOS, the sequence of events begins with IR as the primary contributor, leading to compensatory hyperinsulinemia to maintain normal glycemia. A considerable period during the progression of PCOS is also marked by supraphysiologic insulin levels that may • directly or indirectly disrupt the ovarian function, • stimulate enhanced production of androgens, and • promote the arrest of preantral follicle development. This depicts a bidirectional link between IR and PCOS. The clinical presentation of PCOS is influenced by other insulin-related systemic effects. Women with PCOS and IR are at a significantly increased risk of adverse pregnancy outcomes and chronic diseases such as type 2 diabetes mellitus, cardiovascular diseases, and metabolic syndrome, which thereby seriously affect their physical and psychological health. Therefore, identifying the risk factors that influence the development of IR in PCOS, accurate assessment of insulin sensitivity in the early stages of PCOS, and effective medical intervention for IR in women with PCOS are essential to reduce the risk of long-term complications. Lifestyle modifications are considered a cornerstone in the management of IR in women with PCOS. Implementing calorie-restricted dietary plans and aerobic physical exercise in daily routine may help improve insulin sensitivity in women with PCOS. Sources: Herman R, et al. Int J Mol Sci. 2023;24(4):3140. Zhao H, et al. J Ovarian Res. 2023;16:9.
RkJQdWJsaXNoZXIy MjAwNDg=