Pharmacological management of children with short stature: the role of aromatase inhibitors.

OBJECTIVE: To review the use of aromatase inhibitors, a novel treatment strategy for patients with short stature, which aims at delaying bone age advancement. Skeletal maturation is estrogen-dependent even in male children.

SOURCES: We performed a MEDLINE search of studies published in the last 10 years, including aromatase, short stature, and early puberty as keywords. The most informative articles on indications, dosages, treatment schedules, and side effects of aromatase inhibitors were included in the review.

SUMMARY OF THE FINDINGS: It has become increasingly clear that bone age advancement depends on the production of estrogen and its effect on the growth plate. In boys, testosterone is converted to estradiol by the cytochrome P450 enzyme aromatase. The use of aromatase inhibitors has been shown to be effective in prolonging the length of the growth phase in children with idiopathic short stature, constitutional growth delay, delayed puberty, as well as in children with growth hormone deficiency, in which bone age advancement jeopardizes the results of hormonal replacement therapy with growth hormones. As yet, significant adverse effects have not been reported, and results are encouraging in terms of effective increase in height, whenever the indication for the drug is appropriate.

CONCLUSIONS: Among the pharmacological treatments for short stature, aromatase inhibitors are indicated in cases in which bone age advancement may constitute an obstacle for reaching a final height that is in keeping with the family's target height.