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The Effect of Administering Gonadotropin-Releasing Hormone Agonist with Recombinant-Human Growth Hormone (GH) on the Final Height of Girls with Isolated GH Deficiency: Results from a Controlled Study

Endocrine Unit, Division of Pediatrics, Department of Reproductive Medicine and Pediatrics, University of Pisa, Santa Chiara Hospital, I-56125 Pisa, Italy

Address correspondence and requests for reprints to: Giovanni Federico, M.D., Clinica Pediatrica, Università di Pisa, Ospedale S. Chiara, Via Roma 67, I-56125 Pisa, Italy.

To assess whether delaying puberty may improve final height in GH-deficient children with a poor height prediction at early puberty, we studied 24 girls with isolated GH deficiency until they reached their final height, in a controlled trial. Patients were taking recombinant human GH (r-hGH) substitutive therapy from 2.1 ± 0.5 yr (0.1 IU/kg·day sc) before entering the study, without showing any improvement in height prediction (149.6 ± 2.9 vs.150.3 ± 2.2 cm) on entering puberty. Fourteen girls agreed to add a GnRH agonist (GnRHa) to r-hGH, whereas the remaining 10 decided against it and served as controls. At the start of the study, girls treated with or without GnRHa had similar auxological characteristics (bone age, 10.9 ± 0.6 vs. 10.7 ± 1.3 yr; height SD score for chronological age, -1.87 ± 0.3 vs. -1.82 ± 0.2), including pubertal development. The GnRHa (long-acting D-Trp-6-GnRH) was given at 60 µg/kg im every 28 days for 1.9 ± 0.9 yr, then patients continued the r-hGH at the same dosage (3.1 ± 0.7 yr). At the end of the study, bone age was 16.2 ± 0.3 yr in GnRHa-treated girls and 16.6 ± 0.9 yr in controls. Bone maturation was significantly slower during GnRHa (1.4 ± 0.2 yr), and height SD score for bone age improved (-0.31 ± 0.3) in comparison with controls (2.6 ± 0.4 yr and -1.35 ± 0.3 SD score; P < 0.001 and P < 0.0001, respectively). As a result, girls given the combined therapy reached a final height higher than that of controls (height SD score, -0.39 ± 0.5 vs. -1.45 ± 0.2; P < 0.0001) and also higher than their midparental height (-1.1 ± 0.5; P < 0.0005). Controls reached their midparental height. In conclusion, our results demonstrate that slowing pubertal development with the administration of GnRHa for a limited time may improve final height in GH-deficient girls selected because of a poor height prediction at early puberty.

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