Instead the testosterone response to aromatase inhibitors or selective estrogen receptor modulators merely reinforces that the obesity associated central hypothalamic-pituitary suppression is functional, as serum testosterone concentrations in men with organic congenital or acquired hypothalamic-pituitary pathology (such as congenital hypogonadotropic hypogonadism (e.g., Kalmann syndrome) or destructive mass lesions (e.g., pituitary macroadenoma)) do not increase in response to aromatase inhibitor or SERM treatment. Here, CYP19A1 is linked to obesity due to melanocortin 4 receptor deficiency.