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 trial

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 s ubsequently excluded from the study. Patients were randomly assigned to rec eive 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 (Nutrop in) was administered at a dose of 0.1 U/kg . day sc, until patients reached a bone age (BA) of 14 yr in girls and 16 yr in boys, and LHRH-A (Lupron de pot) was administered at a dose of 300 mu g/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 re sponse to two stimulation tests less than 7 mu g/L, associated with low ser um insulin-like growth factor I and insulin-like growth factor binding prot ein 3 levels. Statistical analysis was performed by ANOVA or Kruskall Walli s when variances were not homogeneous. We observed a significant decrease i n 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) duri ng the 3 years of LHRH-A therapy (P < 0.05). This delay in BA maturation pr oduced a significant gain in final height in the group treated with GH+LHRH -A, which reached - 1.3 +/- 0.5 so score compared with -2.7 +/- 0.3 SD scor e (P < 0.05) in the group treated with GH alone. These results indicate tha t delaying puberty with LHRH-A in GHD children during treatment with GH inc reases final height.