The importance of the action of estrogens on the human male skeleton has been demonstrated convincingly in patients with aromatase (estrogen synthase) deficiency(1–7) and loss of signaling through the ERα receptor.(8) Male patients deficient in either the aromatase enzyme or ERα have exhibited low bone mass and delayed growth plate closure. The gene discussed is CYP19A1; the disease is hyperinsulinemic hypoglycemia, familial, 4.