Divergent pathophysiological drivers of polycystic ovary syndrome: insulin resistance independently fuels the hyperandrogenic phenotype whilst neuroendocrine factors dominate non-hyperandrogenic presentations

Our findings demonstrate that PCOS encompasses two pathophysiologically distinct entities. The Non-HA phenotype appears driven primarily by neuroendocrine dysregulation, whereas the HA phenotype is intrinsically linked to metabolic dysfunction, specifically insulin resistance. Most importantly, we confirm that insulin resistance drives the hyperandrogenic phenotype independently of obesity. These data support a paradigm shift towards phenotype-specific management, necessitating aggressive insulin-sensitising strategies for hyperandrogenic patients regardless of their BMI.