Integrative Network View of PCOS: Organ Crosstalk Driven by the Hyperandrogenemia-Insulin Resistance-Inflammation...

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder affecting women of reproductive age, traditionally attributed to neuroendocrine dysregulation of the hypothalamic-pituitary-ovarian (HPO) axis. However, growing evidence suggests that PCOS is a systemic network disease driven by multi-organ crosstalk. Beyond the HPO axis, adipose tissue, gut microbiota, pancreas, skeletal muscle, thyroid, adrenal glands, and immune organs interact with the ovary through secretion of hormones, metabolites, and inflammatory mediators, forming a complex bidirectional regulatory network. Herein, we propose that the "triad" of hyperandrogenemia, insulin resistance, and chronic inflammation serves as the core pathological axis permeating this network. This multi-organ positive-feedback loop explains the marked phenotypic heterogeneity of PCOS and its propensity to evolve into metabolic syndrome. Accordingly, precision management of PCOS should be redirected toward individualized stratification based on organ-network features. A deeper understanding of these inter-organ crosstalk mechanisms will provide a rationale for developing multi-targeted therapies aimed at the "hyperandrogenemia-IR-inflammation" triad, ultimately improving reproductive and metabolic health throughout women's lives.