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

Abstract

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.

Normo- and hyperandrogenic women with polycystic ovary syndrome exhibit an adverse metabolic profile through life

“…In addition to anovulatory infertility, which is typically associated with the syndrome, women with PCOS exhibit numerous metabolic risk factors, such as abdominal obesity, insulin resistance, impaired glucose tolerance, dyslipidemia, and chronic inflammation (3)(4)(5)(6). Hyperandrogenism (HA) plays a central role in the syndrome and has been associated with a more severe metabolic profile in some, but not all, studies (7)(8)(9)(10)(11). Obesity is common in PCOS and exacerbates the symptoms and promotes negative health consequences by increasing the risks of type 2 diabetes (T2DM) and cardiovascular disease (CVD).…”

Increased Sympathetic Cardiac Autonomic Modulation after Two Consecutive Tilt Tests in Women with Polycystic Ovary Syndrome

“…Excess androgen was also associated with cardiometabolic disorders. 28 It is known that hyperandrogenism and insulin resistance are associated with increased obesity and metabolic disorders, 2,6,7,28,29 and these changes, over time, can predispose patients to the development of cardiovascular diseases. 16,26 Therefore, metabolic alterations such as obesity, diabetes, and visceral fat increase are directly linked to autonomic imbalances, especially increases in sympathetic cardiac autonomic modulation.…”

Association of Cardiometabolic Index and Insulin Resistance with Serum Levels of Peroxisome Proliferator Activated Receptor-γ in Polycystic Ovary Syndrome

“…29 Moreover, according to some studies, hyperandrogenism associated with PCOS is a risk factor for cardiovascular diseases, hypertriglyceridemia, and insulin resistance. [30][31][32][33][34] CMI can be of great help in evaluating such a condition. Hence, relationship of PCOS and CMI can be studied further.…”