Combination GH and Aromatase Inhibitor Therapy Increases Height Potential in Pubertal Boys with ISS

Combining aromatase inhibitors (AIs) and growth hormone (GH) was shown to increase the height potential in pubertal boys with idiopathic short stature (ISS) when compared to treating ISS with either drug separately, according to a study recently published in The Journal of Clinical Endocrinology & Metabolism.

Researchers led by Nelly Mauras, MD, of Nemours Children’s Health System in Jacksonville, Fla. point out that short children’s linear growth is hindered by estrogen’s effect on epiphyseal fusion. “Increasing height potential in growth-retarded children during puberty is often complicated by the inexorable tempo of epiphyseal fusion caused by pubertal sex steroids, greatly limiting the time available for growth,” the authors write.

They write that treatment for ISS with GH has shown positive results, but when administered during puberty there is very limited time to increase height as the growth plates fuse. The investigators set out to look at the safety and efficacy of treating with GH versus AIs (which block the conversion of androgens to estrogens), versus a combination of both. The analyzed the results of 76 pubertal boys around 14 years old, all with ISS (height SDS -2.3), randomized into three cohorts. These participants were treated daily with either AIs, GH, or AIs/GH for two to three years. The boys treated with just AIs for 24 months saw a height increase of 14 cm, those treated with GH for 24 months grew an extra 17.1 cm, and at the patients treated with both saw a height increase of almost 19 cm over 24 months. “Those treated through 36 months grew more,” the authors write. These results contrast with the expected gain in height of a child with a height SDS of -2.0 of +10cm.

Based on these results, the researchers conclude that the combination AI/GH treatment improved linear growth in boys with ISS more than treatment with either AIs or GH alone. “Linear growth was improved further with more prolonged (36 months total) treatment in those with residual growth potential. Regardless of the length of treatment, near-final height gains were: AI, +18.2 (1.6) cm; GH, +20.6 (1.5) cm; and AI/GH, +22.5 (1.4) cm; resulting in the following near-adult height SDS: AI, −1.4 (0.1) cm; GH, −1.4 (0.2) cm; and AI/GH, −1.0 (0.1) cm,” they write. The treatments had an excellent safety profile and no major impact on bone mineralization.