The Impact of Hyperandrogenism in Female Obesity and Cardiometabolic Disease Associated with Polycystic Ovary Syndrome

There is a close association between female obesityFemale obesity and the development of hyperandrogenismHyperandrogenism, insulin resistanceInsulin resistance and cardiometabolic dysfunction. This constellation of clinical features is most notable in women with Polycystic Ovary Syndrome (PCOS)Polycystic ovary syndrome (PCOS), although it also occurs in obeseObese women outside the context of PCOSPolycystic ovary syndrome (PCOS). The underlying mechanisms are complex and multi-directional, and include changes in adipose-related enzyme activities, and the effects of hyperinsulinemia (secondary to insulin resistanceInsulin resistance) as a co-gonadotrophin within the ovarian theca cells. Hyperinsulinemia also enhances adrenal androgen production and the pituitary release of LH, and suppresses the hepatic production of SHBG, thereby increasing the free androgen index. The development of hyperandrogenemia likely promotes a preponderance of visceral adipose tissueAdipose tissue with its attendant effects on enhanced insulin resistanceInsulin resistance and cardiometabolic riskCardiometabolic risk. The close association of weight gain and female obesityFemale obesity with hyperandrogenismHyperandrogenism and cardiometabolic dysfunction provides a rationale for effective and sustained weight-loss as an excellent management strategy. This may be combined, in some women, with the administration of an anti-androgen therapy and/or metformin. In the current era of designer GLP1 dual and triple incretin agonist therapies, these molecules should be explored further in the context of women with PCOS and female obesityFemale obesity in general, to assess their adequacy for alleviating androgenicity and associated cardiometabolic riskCardiometabolic risk.