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

• 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: This was a prospective, double-blind, randomized, placebo (Pl)-controlled clinical study. SETTING: The study was performed at a university hospital out-patient clinic. PATIENTS: Thirty-one boys, aged 9.0-14.5 yr, with ISS were studied. INTERVENTION: The boys were treated with the aromatase inhibitor letrozole (Lz; 2.5 mg/d) or Pl for 2 yr. MAIN OUTCOME MEASURE: The main outcome measure was the change in PAH after 24 months of treatment. RESULTS: PAH increased by 5.9 cm (P < 0.0001), and height SD score for bone age increased by 0.7 SD score (P < 0.0001) in the Lz-treated boys, whereas no changes occurred in the respective measures in Pl-treated boys. Areal bone mineral density of the lumbar spine and femoral neck, assessed by dual-energy x-ray absorptiometry, increased in a similar fashion in both groups during the treatment, whereas bone mineral apparent density increased only in those taking Lz (median increase, 4.3%; P = 0.009). CONCLUSIONS: Treatment with the aromatase inhibitor Lz delays bone maturation and improves PAH in boys with ISS. No adverse effects on bone mineralization were evident after 2 yr of treatment.

Nyckelord

Adolescent

Aromatase Inhibitors/*therapeutic use

Body Height/*drug effects

Bone Density/drug effects

Child

Densitometry

X-Ray

Double-Blind Method

Estrogen Antagonists/*therapeutic use

Femur Neck/metabolism/radiography

Growth/drug effects

Growth Disorders/*drug therapy/metabolism/physiopathology/radiography

Hormones/blood

Humans

Lumbar Vertebrae/metabolism/radiography

Male

Nitriles/*therapeutic use

Prognosis

Puberty

Research Support

Non-U.S. Gov't

Triazoles/*therapeutic use

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)