Over the course of five years, Dr. Xi Huang’s lab conducted a series of in vitro and in vivo experiments to define the mechanism of interaction between estradiol—the strongest of the three estrogens—and hepcidin, the main iron regulatory hormone. (Low hepcidin production leads to iron overload, while high hepcidin leads to iron restriction.) Knowing that estradiol appears to inhibit hepcidin as a mechanism to compensate iron loss during menstruation, Dr. Huang and his team investigated whether changes in estradiol levels would lead to changes in iron levels. If estrogen’s relationship to hepcidin was the defining factor in the iron storage levels after menopause—when the ovaries stop producing hepcidin-inhibiting estrogen—iron storage levels should be observed to be lower. The fact that iron storage levels in post-menopausal women is higher verifies that increased iron found in the skin of postmenopausal women is not directly caused by estrogen deficiency. By process of elimination, the cessation of menstruation is the cause of increased iron storage. This important distinction means that it is possible to target the cause of accelerated skin aging without risky estrogen therapy.