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Near Final Height in Pubertal Growth Hormone (GH)-Deficient Patients Treated with GH Alone or in Combination with Luteinizing Hormone-Releasing Hormone Analog: Results of a Prospective, Randomized Trial¹

Institute of Maternal and Child Research (M.V.M., M.E., A.A., F.C.), University of Chile, Santiago, Chile; and DEB, NICHD (G.B.C.), National Institutes of Health, Bethesda, Maryland 20892

Address correspondence and requests for reprints to: M. Verónica Mericq, IDIMI, University of Chile, Casilla 226-3, Santiago, Chile.

To study the effects of delaying puberty in GH-deficient (GHD) children, we studied 21 GHD (9 boys, 14 girls), treatment-naive, pubertal patients in a prospective, randomized trial. Their chronological age was 14.3 ± 1.6 yr, and their bone age was 11.3 ± 1.1 yr (mean ± SD) at the beginning of the study. Four patients who developed hypogonadotropic hypogonadism were subsequently excluded from the study. Patients were randomly assigned to receive GH + LH-releasing hormone analog (LHRH-A) (n = 7), or GH alone (n = 10). GH and LHRH-A treatment started simultaneously in each patient. GH (Nutropin) was administered at a dose of 0.1U/kg·day sc, until patients reached a bone age (BA) of 14 yr in girls and 16 yr in boys, and LHRH-A (Lupron depot) was administered at a dose of 300 µg/kg·every 28 days in during 3 yr. We defined GH deficiency as patients with a growth velocity less than 4 cm/yr, BA delay more than 1 yr in relationship to chronological age, GH response to two stimulation tests less than 7 µg/L, associated with low serum insulin-like growth factor I and insulin-like growth factor binding protein 3 levels. Statistical analysis was performed by ANOVA or Kruskall Wallis when variances were not homogeneous. We observed a significant decrease in the rate of BA maturation in the group treated with GH+LHRH-A (1.5 ± 0.2 yr) compared with the group treated with GH alone (4.2 ± 0.5 yr) during the 3 years of LHRH-A therapy (P < 0.05). This delay in BA maturation produced a significant gain in final height in the group treated with GH+LHRH-A, which reached -1.3 ± 0.5 SD score compared with -2.7 ± 0.3 SD score (P < 0.05) in the group treated with GH alone. These results indicate that delaying puberty with LHRH-A in GHD children during treatment with GH increases final height.

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