INS and obesity due to melanocortin 4 receptor deficiency: A bidirectional pathogenic link is present between metabolic syndrome (MetS) and hypogonadism, as reduced testosterone predicts MetS and the presence of MetS at study entry increased the risk of hypogonadism development, as described by Popovic et al. Insulin sensitizer treatment in MetS as well as weight loss in obesity resulted in an increase in serum testosterone, while testosterone substitution resulted in the improvement in metabolic derangements characteristic of MetS [116,117].