Is anastrazole (Aromatase Inhibitor) effective for treating short stature?

From the Guidelines

Anastrozole should not be used as a first-line treatment for short stature due to its limited effectiveness and potential side effects, and its use should only be considered after consultation with a pediatric endocrinologist in specific circumstances, such as in adolescent boys with constitutional delay of growth and puberty or idiopathic short stature, at doses of 1-2 mg daily, as supported by the study 1. The medication works by blocking the conversion of testosterone to estrogen, which can delay growth plate closure and potentially allow for additional height gain. However, evidence supporting its use is modest at best, with studies showing variable results and height gains generally limited to 1-3 cm in final adult height. Some key points to consider when evaluating the use of anastrozole for short stature include:

• The potential benefits of treatment, including increased height gain and improved growth velocity
• The potential risks and side effects, including reduced bone mineral density, joint pain, and potential impacts on cognitive development
• The need for careful monitoring and evaluation by a pediatric endocrinologist to determine the appropriateness of treatment and to minimize potential risks
• The importance of considering alternative treatments, such as growth hormone therapy, which remains the FDA-approved first-line treatment for most causes of short stature in children. It is also worth noting that anastrozole is not FDA-approved for the treatment of short stature, and its use in this context is considered off-label, as mentioned in the study 1. Overall, while anastrozole may have some potential benefits in the treatment of short stature, its use should be approached with caution and careful consideration of the potential risks and benefits, and only after consultation with a pediatric endocrinologist, as supported by the study 1.

From the FDA Drug Label

The efficacy of anastrozole in the treatment of pubertal gynecomastia in adolescent boys and in the treatment of precocious puberty in girls with McCune-Albright Syndrome has not been demonstrated. A small but statistically significant reduction of growth rate from 7.9 ± 2.9 cm/year to 6.5 ± 2. 8 cm/year was observed but the absence of a control group precludes attribution of this effect to treatment or to other confounding factors such as variations in endogenous estrogen levels commonly seen in McCune-Albright Syndrome patients. There were no clinically significant changes in Tanner staging,mean ovarian volume, mean uterine volume and mean predicted adult height.

The FDA drug label does not answer the question.

From the Research

Effectiveness of Anastrazole for Short Stature

• Anastrazole, an aromatase inhibitor, has been studied as a potential treatment for short stature in children and adolescents 2, 3, 4, 5, 6.
• The use of anastrazole in treating short stature is based on its ability to block estrogen biosynthesis, thereby postponing the fusion of growth plates and allowing for continued longitudinal growth 2.
• Studies have shown that treatment with anastrazole can effectively delay bone maturation and increase predicted adult height in boys with constitutional delay of growth and puberty, idiopathic short stature, and growth hormone deficiency 2, 3, 4.

Comparison with Letrozole

• Anastrozole has been compared to letrozole, another aromatase inhibitor, in terms of its effectiveness in augmenting height in short pubertal males 3, 4.
• One study found that anastrozole resulted in a greater increase in predicted adult height after 1 year of treatment, although the difference was not significant after 2-3 years 3, 4.
• Another study found that letrozole was more potent in hormonal manipulation than anastrozole, but anastrozole caused fewer deviations in hormone levels and growth velocity 4.

Combination with Growth Hormone

• Anastrazole has also been studied in combination with growth hormone (GH) in treating adolescent boys with short stature 5, 6.
• One study found that the combination of anastrazole and GH was effective in delaying bone age and improving predicted adult height, although it also increased the risk of adverse reactions such as elevated uric acid and decreased high-density lipoprotein (HDL) 5.
• Another study found that the combination of anastrozole and GH, started at the very end of puberty, allowed boys with idiopathic short stature to reach a greater adult height than GH alone 6.

Safety and Efficacy

• The safety and efficacy of anastrazole in treating short stature are still being studied, and its use is considered experimental until more data is available 2, 4.
• Long-term follow-up data is needed to determine the potential benefits and risks of anastrazole treatment in children and adolescents with short stature 2, 4.