Strategies for Maximizing Growth in Puberty in Children with Short Stature

The approach to the child with growth retardation who is in puberty remains an important clinical challenge. The use of high-dose growth hormone (GH), suppression of puberty with GnRH analogs in combination with GH, and the use of selective inhibitors of the aromatase enzyme with aromatase inhibitors (also in combination with GH) are all therapeutic choices that have been studied. Aromatase blockade effectively blocks estrogen production in males with a reciprocal increase in testosterone, and a new generation of aromatase inhibitors, including anastrozole, letrozole and exemestane, is under investigation in adolescent subjects with severe growth retardation. This class of drugs, if judiciously used for a window of time, offers promise as an adjunct treatment of growth delay in pubertal patients with GH deficiency, idiopathic short stature, testotoxicosis, and other disorders of growth. These evolving uses of aromatase inhibitors, however, represent off-label use of the product, and definitive data on their efficacy are not available for each of the conditions mentioned. Safety issues regarding bone health also require further study.