Insulin resistance in polycystic ovary syndrome phenotypes and the vicious cycle model in its etiology

Polycystic ovary syndrome (PCOS) is a multifactorial disorder driven by at least three pathophysiological components: hypothalamic, ovarian, and obesity-related mechanisms. Insulin resistance (IR) is a unifying feature. Reciprocal interactions among androgen excess, hyperinsulinemia, and reduced hepatic sex hormone-binding globulin production create a self‑sustaining "vicious cycle" that exacerbates PCOS manifestations, which vary in severity and define four clinical phenotypes. To evaluate insulin resistance across PCOS phenotypes A (HA + OD + PCOM), B (HA + OD), C (HA + PCOM), and D (OD + PCOM). A retrospective observational study (2018-2022) of 200 Caucasian women aged 18-36 diagnosed with PCOS according to the Rotterdam criteria. Insulin resistance was assessed using HOMA‑IR. Clinical and anthropometric variables, Free Androgen Index (FAI), and Ferriman‑Gallwey (mFG) scores were analyzed by phenotype. Insulin resistance was present in 57.5% of participants. HOMA‑IR showed no correlation with PCOS duration but differed significantly between phenotypes. Mean HOMA‑IR values exceeded reference thresholds in all phenotypes: A 3.59, B 2.59, C 2.05, D 2.73. Moderate to strong positive correlations were observed between HOMA‑IR and mean arterial pressure, pulse rate, and waist‑to‑hip ratio, indicating an association with cardiometabolic risk across phenotypes. Positive associations among FAI, HOMA‑IR, and mFG score support a contribution of ovarian androgens to insulin resistance and hirsutism. Insulin resistance predominated in this PCOS cohort and was phenotype‑dependent rather than related to syndrome duration. All phenotypes exhibited elevated HOMA‑IR, with phenotype A showing the highest and phenotype C the lowest mean values. The proposed "vicious cycle" model integrates hyperandrogenism and hyperinsulinemia in peripheral insulin resistance; further research into genetic and intracellular signaling mechanisms is warranted.