Is anastrazole (generic name: anastrazole) suitable for treating pediatric short stature?

Anastrozole for Pediatric Short Stature: Limited Evidence and Not FDA-Approved

Anastrozole is not FDA-approved for treating pediatric short stature and should not be used as first-line therapy for this condition due to limited evidence on long-term safety and efficacy.

Current Evidence on Anastrozole for Short Stature

Anastrozole is an aromatase inhibitor that works by blocking the conversion of androgens to estrogens, potentially delaying epiphyseal growth plate closure. While this mechanism theoretically could extend growth potential, the evidence supporting its use in pediatric short stature is limited:

• A 2019 guideline mentions anastrozole as a potential research area for severely growth-restricted adolescents on long-term dialysis, but not as an established treatment 1
• Current research on anastrozole for height augmentation shows mixed and limited results:
  • A recent study comparing anastrozole with letrozole in boys with idiopathic short stature found minimal change in predicted adult height after 2-3 years of treatment 2
  • Another study showed that while anastrozole was less potent in hormonal manipulation than letrozole, it actually resulted in greater improvement in predicted adult height after one year 3

FDA-Approved Indications for Anastrozole

Anastrozole is currently FDA-approved only for:

• Breast cancer risk reduction in postmenopausal women at increased risk 1
• Treatment of hormone receptor-positive breast cancer in postmenopausal women 1

Growth Hormone Remains First-Line Therapy

For children with short stature, growth hormone (GH) therapy remains the established first-line treatment when indicated:

• GH is indicated for children with chronic kidney disease stages 3-5 or on dialysis when height is below the 3rd percentile 4
• GH therapy is also indicated for children with genetic syndromes including SHOX gene-related disorders 4

Specific Clinical Scenarios Where Anastrozole Has Been Studied

Anastrozole has shown some promise in specific conditions:

1. Congenital Adrenal Hyperplasia (CAH):

   • Anastrozole decreased bone age advancement in children with CAH and advanced bone age without adverse effects on bone mineral density 5, 6
   • In 60 patients with CAH, anastrozole improved predicted adult height Z-scores from -2.1 to -0.45 at 4 years 5

2. Combination Therapy:

   • Recent research suggests that combining anastrozole with recombinant human growth hormone may be more effective than letrozole or GnRH analogs for adolescent males with idiopathic short stature 7

Safety Concerns

Several safety concerns exist with anastrozole use in pediatric populations:

• Potential negative effects on bone mineral density
• Alterations in hormone levels
• Unknown long-term safety profile in growing children
• Possible effects on cognitive and emotional development

Monitoring Requirements If Used Off-Label

If anastrozole is considered in exceptional circumstances:

• Baseline fracture risk assessment and bone mineral density measurement before initiation 1
• Regular monitoring of bone age every 6-12 months
• Monitoring of hormone levels (testosterone, estradiol)
• Careful assessment of growth velocity and predicted adult height
• Bone-protective measures including adequate calcium and vitamin D supplementation 1

Conclusion

While anastrozole shows some promise in specific conditions like CAH or as an adjunct to growth hormone in selected cases, it should not be considered a standard treatment for pediatric short stature. Growth hormone therapy remains the established treatment for most causes of pediatric short stature, with better documented safety and efficacy profiles.