Cardiometabolic Risk in PCOS: More than a Reproductive Disorder

Abstract

Purpose of review: Polycystic ovary syndrome (PCOS) is diagnosed by its characteristic reproductive features. However, PCOS is also associated with metabolic abnormalities, including insulin resistance and β-cell dysfunction. The severity of these abnormalities varies according to the reproductive phenotype, with the so-called NIH or classic phenotype conferring the greatest metabolic risk. The increased risk for type 2 diabetes (T2D) is well established among affected women with the NIH phenotype, but whether PCOS also confers an increased risk for cardiovascular events remains unknown.

Recent findings: Recent studies in daughters of affected women have found evidence for pancreatic β-cell dysfunction prior to menarche. Further, genetic analyses have provided evidence that metabolic abnormalities such as obesity and insulin resistance contribute to the pathogenesis of PCOS. PCOS increases the risk for T2D. However, the risk for cardiovascular disease has not been quantified, and prospective, longitudinal studies are still critically needed.

Keywords: Cardiovascular disease; Insulin resistance; Obesity; Polycystic ovary syndrome; Type 2 diabetes.

Figure 1. Defects in Disposition Index (DI) Observed in Premenarchal PCOS Daughters

Pictured data from PCOS daughters and control girls of comparable age, BMI, and pubertal stage. All girls were aged 8 to 12 years of age and breast Tanner Stage I-III. Frequently-sampled IV glucose tolerance test (FSIGT)-derived measure of insulin sensitivity (Sensitivity Index, SI) plotted on the X axis, measure of insulin secretion (Acute Insulin Response to Glucose, AIRg) plotted on the Y axis. The product of SI and AIRg is termed the disposition index (DI) and is a measure of β-cell function. In the normally functioning β-cell, the relationship between insulin sensitivity and secretion follows a hyperbolic pattern. Hyperbolic line fit for the control girl data, the PCOS daughter data are plotted individually (open circles). PCOS daughters with dysglycemia denoted by black circles. Most PCOS daughters had a DI below the control population average indicating that they are at high risk to progress to type 2 diabetes [41]. Figure originally published in [9], used with permission.