The impact of hyperandrogenism in female obesity and cardiometabolic diseases associated with polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) is a common condition characterized by reproductive and hyperandrogenic features and is often associated with obesity and metabolic dysfunction. Overall, women with PCOS have a substantially greater prevalence of metabolic syndrome than women from the general population. Furthermore, PCOS per se (independent of its frequent association with obesity) often confers cardiometabolic risk (including insulin resistance), and its concurrence with obesity often represents a metabolic "double-whammy" from the adverse effects of PCOS and obesity. The introduction of the Rotterdam diagnostic criteria for PCOS in 2003 has broadened the scope of this condition. The Rotterdam diagnostic criteria have also introduced two new phenotypic subgroups (including normoandrogenemic women with PCOS) that have provided novel insights into a potential role for hyperandrogenism in the development of adverse cardiometabolic risk in women with PCOS. Based on evidence from cross-sectional and interventional studies, hyperandrogenism, obesity, and cardiometabolic risk in women appear to be linked through complex and multidirectional pathways. Furthermore, data from obese women without a formal diagnosis of PCOS also suggest that these interrelationships often exist in female obesity per se (in milder forms than occurs in PCOS). Data from female-to-male transsexuals are particularly informative because these show direct effects of hyperandrogenism (induced through exogenous use of androgenic therapies) on fat distribution and cardiometabolic risk in women. A challenge for the future will be to disentangle and improve our understanding of this complex pathogenic web, thereby facilitating novel and targeted therapies for the hyperandrogenic and adverse cardiometabolic manifestations of PCOS