The effects of obesity and hypogonadism form a vicious cycle, whereby dysregulation of the hypothalamic–pituitary–testicular axis—due to the effect of the release of multiple mediators, thus decreasing GnRH release from the GnRH neurons of the hypothalamus—causes decreases in LH and FSH levels. The gene discussed is PLOD1; the disease is obesity due to melanocortin 4 receptor deficiency.