Aromatase, an
enzyme located in the endoplasmic reticulum of
estrogen-producing cells, catalyzes the rate-limiting step in the conversion of
androgens to
estrogens in many tissues. The clinical features of patients with defects in CYP19A1, the gene encoding
aromatase, have revealed a major role for this
enzyme in epiphyseal plate closure, which has promoted interest in the use of inhibitors of
aromatase to improve adult height. The availability of the selective
aromatase inhibitors letrozole and
anastrozole--currently approved as adjuvant
therapy for
breast cancer--have stimulated
off-label use of
aromatase inhibitors in pediatrics for the following conditions: hyperestrogenism, such as
aromatase excess syndrome,
Peutz-Jeghers syndrome,
McCune-Albright syndrome and functional follicular
ovarian cysts;
hyperandrogenism, for example,
testotoxicosis (also known as
familial male-limited precocious puberty) and
congenital adrenal hyperplasia; pubertal
gynecomastia; and short stature and/or pubertal delay in boys. Current data suggest that
aromatase inhibitors are probably effective in the treatment of patients with
aromatase excess syndrome or
testotoxicosis, partially effective in Peutz-Jeghers and
McCune-Albright syndrome, but probably ineffective in
gynecomastia. Insufficient data are available in patients with
congenital adrenal hyperplasia or functional
ovarian cysts. Although
aromatase inhibitors appear effective in increasing adult height of boys with short stature and/or pubertal delay, safety concerns, including vertebral
deformities, a decrease in serum
HDL cholesterol levels and increase of
erythrocytosis, are reasons for caution.