Management of short stature with GnRH agonist and co-treatment with growth hormone: A controversial issue

Adolescent growth is the focus of several interventions aimed at increasing the amplitude of the adolescent spurt. Favorable results with GnRH agonists in precocious puberty have encouraged attempts to increase the duration of the adolescent growth spurt by delaying normal puberty in short individuals using GnRH agonists with or without growth hormone. These approaches remain highly controversial, have not been validated and approved for use by regulatory authorities and were the topic of a session at the 6th International Conference on the Onset of Puberty. Here we review the available information on the efficacy and safety of this approach. GnRH agonists, when used outside the context of precocious puberty, induce a modest gain when used for extended periods of time. Several trials have now shown that growth hormone alone can modestly increase adult height in short adolescents with idiopathic short stature or in those born small for gestational age. The association of growth hormone and GnRH agonists still lacks a definite demonstration of its additional efficacy and available results do not allow firm conclusions. In conclusion, watchful waiting or sex steroids in delayed puberty are generally the best options in short children presenting around puberty. However, long-term and adequately powered clinical trials, focusing on efficacy, safety and clinical significance are needed to fully evaluate the combination of growth hormone and GnRH agonists in short adolescents. In the meanwhile, these approaches should be considered as experimental.