ESR1 and obesity due to melanocortin 4 receptor deficiency: 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.