Combined treatment with gonadotropin-releasing hormone analog and growth hormone in central precocious puberty.

Abstract

GnRH analogs (GnRHa) arrest pubertal development and slow growth velocity (GV) and bone maturation, thus improving adult height in central precocious puberty (CPP). In some patients, however, GV decreases to such an extent that it compromises the improvement in predicted adult height (PAH). Fourteen children (10 girls and 4 boys) with idiopathic CPP whose GV during GnRHa treatment decreased below the 25th percentile for chronological age with no improvement in PAH received GH at a dose of 0.3 mg/kg week, sc, 6 days/week for 2-3 yr. Fourteen children (10 girls and 4 boys) with idiopathic CPP, matched for bone age (BA), chronological age, and duration of GnRHa treatment, who showed the same growth deceleration but refused GH treatment, served as the control group. In girls, GV as so score for BA improved from -3.4 +/- 0.5 to -2.5 +/- 0.5 after 3 yr of combined treatment; PAH significantly improved from 152.7 +/- 1.7 cm (before GnRHa) and 153.5 +/- 1.7 cm (before GnRHa and GH) to 167.1 +/- 3.0 cm after 3 yr of combined treatment (P < 0.01 vs. pretreatment with GnRHa plus GH). In boys, GV as SD score for BA remained unchanged from -2.0 +/- 1.0 to -2.2 +/- 1.2 after 2 yr of combined treatment; PAH increased from 166.6 +/- 4.8 cm (before GnRHa) and 166.2 +/- 4.9 (before GnRHa plus GH) to 171.1 +/- 6.1 cm after 2 yr (P = NS). In the control group, in girls after 6 yr of GnRHa treatment, height in SD score for BA improved from -1.0 +/- 0.3 to -0.1 +/- 0.4 (P = NS), and PAH significantly improved from 155.5 +/- 2.0 to 161.5 +/- 2.1 cm (P < 0.05); in boys after 4 yr of GnRHa treatment, height in SD score for BA improved from -1.1 +/- 0.3 to -0.3 +/- 0.4 (P = NS), and PAH changed from 172.6 +/- 3.6 to 170.3 +/- 3.6 cm (P = NS). Eight of 10 girls receiving GH plus GnRHa treatment had an actual height higher than PAH and their target height. The results of our long term study indicate that in children with CPP who show a marked decrease in GV during GnRHa treatment, GH administration remarkably improves growth velocity and predicted adult height, especially in girls.