Of note, studies reporting that inhibiting oestradiol production or action via administration of aromatase inhibitors [43] or selective estrogen receptor modulators (SERMs) [44] increase LH and serum testosterone cannot be used to invoke a pathogenetic role for oestradiol in obesity associated HPT axis suppression, as similar effects have been reported in lean men [45]. Here, ESR1 is linked to obesity due to melanocortin 4 receptor deficiency.