INS and obesity due to melanocortin 4 receptor deficiency: Along with advanced age and other factors, obesity is a significant risk factor for T deficiency in males.37 This is due to obesity-induced increases in levels of leptin, insulin, proinflammatory cytokines, and estrogen, which can cause a functional hypogonadotropic hypogonadism resulting in disruption of the hypothalamic gonadotrophin-releasing hormone neurons.37,38 Obesity has been shown to decrease T levels as much as 40% compared with controls.38