POMC and metabolic disease: Different investigations have indicated that premenopausal women exhibit many less metabolic disorders than men, including lower incidence of IR, although this effect diminishes severely when women reach the postmenopausal situation.67,68 Specifically, female sex hormones including estradiol (e.g., 17β-oestradiol)69 protect female proopiomelanocortin (POMC) neurons from IR by enhancing POMC neuronal excitability and coupling insulin receptors to transient receptor potential (TRPC) channel activation.