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This version published online on September 27, 2005
Journal of Clinical Endocrinology & Metabolism, doi:10.1210/jc.2005-1392
A more recent version of this article appeared on December 1, 2005
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*Compound via MeSH
*Substance via MeSH
Medline Plus Health Information
*Growth Disorders

Submitted on June 23, 2005
Accepted on September 20, 2005

Inhibition of estrogen biosynthesis with a potent aromatase inhibitor increases predicted adult height in boys with idiopathic short stature: a randomized controlled trial

Matti Hero, Ensio Norjavaara, and Leo Dunkel*

Hospital for Children and Adolescents, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland; Göteborg Pediatric Growth Research Center, Institute for the Health of Women and Children, Göteborg University, Göteborg, Sweden; Department of Pediatrics, Kuopio University Hospital, Kuopio Finland

* To whom correspondence should be addressed. E-mail: leo.dunkel{at}kuh.fi.

Context: In males as well as in females, estrogen is an essential regulator of bone maturation, growth plate fusion and cessation of longitudinal growth. Therefore, an increase in predicted adult height (PAH) may be achieved in short boys by blocking estrogen biosynthesis.

Objective: We tested the hypothesis that a decrease in the rate of bone maturation and an increase in PAH can be achieved in boys with idiopathic short stature (ISS) by the method of blocking estrogen biosynthesis with an aromatase inhibitor. Secondarily, we investigated the effects of aromatase inhibition on bone mineralization.

Design: Prospective, double-blind, randomized, placebo-controlled clinical study.

Setting: University hospital outpatient clinic.

Patients: 31 boys, aged 9.0-14.5 yr, with ISS.

Intervention: Treatment with the aromatase inhibitor letrozole (2.5 mg/d) or placebo, for 2 yr.

Main outcome measure: Change in PAH after 24 months of treatment.

Results: PAH increased by 5.9 cm (P < 0.0001) and height SD for bone age by 0.7 SD (P < 0.0001) in the letrozole-treated boys, while no changes occurred in the respective measures in placebo-treated boys. Areal bone mineral density of the lumbar spine and femoral neck, assessed by DEXA, increased in a similar fashion in both groups during the treatment, while bone mineral apparent density increased only in those on letrozole (median increase 4.3%; P = 0.009).

Conclusions: Treatment with the aromatase inhibitor letrozole delays bone maturation and improves PAH in boys with ISS. No adverse effects on bone mineralization were evident after 2 yr of treatment.
Key words: aromatase inhibition • estrogen • bone maturation • growth • bone mineral density




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