From the Guidelines
Aromatase inhibitors should not be used as a routine treatment for height augmentation in boys due to their potential to cause significant side effects and disrupt normal pubertal development. The use of aromatase inhibitors (AIs) like anastrozole, letrozole, and exemestane for height augmentation in boys is associated with several problems, including decreased bone mineral density, joint pain, and abnormal lipid profiles with increased LDL cholesterol 1. These medications can also disrupt normal pubertal development and may cause psychological effects, making their use in adolescents a concern due to the lack of long-term safety data, as they were primarily developed for adult cancer treatment 1. While AIs may delay epiphyseal closure by reducing estrogen conversion from testosterone, potentially adding 1-3 inches to final height, the benefits are outweighed by the considerable risks, especially when considering the potential for severe adverse effects, severe illness, or trauma 1. Treatment with AIs typically involves daily medication for 1-3 years during puberty, requiring regular monitoring of bone density, lipid profiles, and growth parameters, which should only be considered under specialist endocrinology supervision for boys with documented short stature and rapid pubertal progression 1. The risk-benefit ratio often does not justify the use of AIs outside specific clinical scenarios with careful monitoring, and alternative treatments such as growth hormone therapy may be more effective in improving adult height, with a median absolute increase of 7.4 cm in boys and 7.0 cm in girls on various modes of renal replacement therapy 1. Key considerations for the use of AIs in boys include:
- Potential side effects: decreased bone mineral density, joint pain, abnormal lipid profiles
- Disruption of normal pubertal development and potential psychological effects
- Lack of long-term safety data in adolescents
- Need for regular monitoring and specialist supervision
- Alternative treatments may be more effective in improving adult height.
From the FDA Drug Label
The growth of some cancers of the breast is stimulated or maintained by estrogens. Letrozole is a nonsteroidal competitive inhibitor of the aromatase enzyme system; it inhibits the conversion of androgens to estrogens.
The problems associated with aromatase inhibitors, such as letrozole, for increasing height in boys are not directly stated in the drug label. However, based on the mechanism of action, inhibition of estrogen biosynthesis may affect growth and development.
- Estrogen plays a role in regulating growth plates, and its suppression may impact bone growth.
- The label does not provide information on the use of letrozole for increasing height in boys, and its effects on growth and development in this population are unknown 2.
From the Research
Problems Associated with Aromatase Inhibitors
- Aromatase inhibitors can cause various side effects, including elevated uric acid, decreased high-density lipoprotein (HDL), severe acne, excitement, hyperactivity, irritability, knee pain, and fracture 3
- Letrozole, a type of aromatase inhibitor, can cause higher testosterone and lower estradiol levels compared to anastrozole, another type of aromatase inhibitor 4, 5
- Aromatase inhibitors may not increase adult height in pre and peripubertal boys with idiopathic short stature (ISS) when treated for 2 years and re-assessed 4 years after treatment 5
- The use of aromatase inhibitors in pediatric patients is still considered experimental due to the lack of long-term follow-up data on their safety and efficacy, particularly their effects on bone development 6
- Aromatase inhibitors can cause vertebral abnormalities, and the prevalence of these deformities should be evaluated prospectively in patients treated with these inhibitors 5
- Combination therapy with aromatase inhibitors and growth hormone (GH) can increase height potential in pubertal boys with idiopathic short stature (ISS), but the safety profile of this treatment should be closely monitored 7
- Aromatase inhibitors can cause changes in lipid metabolism, including decreased HDL, and can also cause mild renal dysfunction, impaired fasting glucose, and granulocytopenia 3