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.