INS and Obesity: Numerous hypotheses have been proposed to account for the unfavorable prognostic implications of obesity, including concentrations of circulating hormones such as estrogen and androgens, reduced levels of sex hormone-binding globulin which elevate free estradiol and free testosterone, elevated levels of insulin and insulin-like growth factor, diminished levels of insulin-like growth factor binding protein, elevated levels of cortisol and leptin, augmented levels of cytokines, disrupted lipid metabolism, and heightened levels of inflammation culminating in compromised immune function.20