Polycystic ovary syndrome: insight into pathogenesis and a common association with insulin resistance

Abstract

Polycystic ovary syndrome (PCOS) is a common condition that typically develops in reproductive-age women. The cardinal clinical and biochemical characteristics of PCOS include reproductive dysfunction and hyperandrogenic features. PCOS is also strongly associated with obesity based on data from epidemiological and genetic studies. Accordingly, PCOS often becomes manifest in those women who carry a genetic predisposition to its development, and who also gain weight. The role of weight gain and obesity in the development of PCOS is mediated at least in part, through worsening of insulin resistance. Compensatory hyperinsulinaemia that develops in this context disrupts ovarian function, with enhanced androgen production and arrest of ovarian follicular development. Insulin resistance also contributes to the strong association of PCOS with adverse metabolic risk, including dysglycaemia, dyslipidaemia and fatty liver. Conversely, modest weight loss of just 5% body weight with improvement in insulin sensitivity, frequently results in clinically meaningful improvements in hyperandrogenic, reproductive and metabolic features. Future developments of novel therapies for obese women with PCOS should focus on promotion of weight loss and improvement in insulin sensitivity. In this context, therapies that complement lifestyle changes such as dietary modification and exercise, particularly during the maintenance phase of weight loss are important. Putative novel targets for therapy in PCOS include human brown adipose tissue

Lipids and insulin regulate mitochondrial‐derived peptide (MOTS‐c) in PCOS and healthy subjects

“…Intralipid administration elevates circulating FFA levels that have deleterious effects in humans, promotes proinflammatory cytokine TNFα secretion, interferes with glucose metabolism, obstructs glucose oxidation and reduces glucose disposal rate . As a consequence, this promotes hepatic and peripheral IR More than 50% of women with PCOS have lower IS and higher IR compared with healthy women. The metabolic pathways responsible for this contrasting IR profile are not completely understood.…”

“…3 PCOS women have elevated levels of cardiovascular disease risk (CVD) factors including type 2 diabetes (T2DM), carotid intima-media wall thickness and platelet dysfunction. 4 Weight loss improves many clinical features of PCOS, including menses regularity and fertility, 5 and reduces CVD risk factors and IR 6 Cellular mechanisms leading to IR in PCOS are not clearly understood. Adipose tissue dysfunction and dysregulated expression of adipokines have been implicated in the pathophysiology of PCOS.…”

Alteraciones metabólicas sutiles en adolescentes con obesidad y síndrome de ovario poliquístico

“…Se ha reportado que el hiperandrogenismo clínico o bioquí-mico se observa en alrededor del 70% de las pacientes, mientras que el 27% presenta disfunción ovulatoria y en alrededor del 20% de las pacientes con SOP se documenta la presencia de ovarios de aspecto poliquístico por ultrasonografía acorde con los criterios vigentes, y la prevalencia de resistencia a la insulina (RI) es variable 5 . La interacción del exceso de andrógenos, el alto índice de masa corporal (IMC) y la RI en pacientes con SOP forma parte de la fisiopatología de este sín-drome.…”

Severe insulin resistance: pathologies

“…Epidemiological studies support the relationship between obesity and PCOS, further evidenced by observations that modest weight loss can reduce the manifestations of the disease . Insulin resistance appears to be an important contributor to the pathogenesis of PCOS, mediating androgen secretion . Insulin resistant states other than those observed in obese individuals are associated with ovarian dysfunction that bears many of the hallmarks of PCOS .…”