Aromatase deficiency in men: a clinical perspective

Abstract

Human aromatase deficiency is a very rare syndrome characterized by congenital estrogen deprivation that is caused by loss-of-function mutations in CYP19A1, which encodes aromatase. Here, we review the presentation, diagnosis and treatment of aromatase deficiency in men to provide useful advice for clinical management of the condition. At presentation, all men with aromatase deficiency have tall stature, delayed bone maturation, osteopenia or osteoporosis and eunuchoid skeletal proportions. Diagnosis of the condition is supported by the presence of unfused epiphyses and undetectable serum estradiol levels; the condition can be further substantiated by genetic sequencing of CYP19A1. Transdermal estradiol treatment at a daily dose of about 25 microg might be adequate for lifelong replacement therapy. BMD and levels of serum estradiol, luteinizing hormone and testosterone should be monitored carefully and considered powerful biochemical markers of adequate estrogen substitution in clinical practice. Early diagnosis is important to initiate estrogen therapy as soon after puberty as possible to avoid the skeletal complications that are associated with this condition.