Adult height in short normal girls treated with gonadotropin-releasing hormone analogs and growth hormone

Abstract

Combined treatment with GH and GnRH analogs (GnRHa) has been proposed to improve final adult height in true precocious puberty, GH deficiency, and short normal subjects with early or normal timing of puberty with still controversial results. We treated 12 girls with idiopathic short stature and normal or early puberty with GH and GnRHa and followed them to adult height; 12 girls comparable for auxological and laboratory characteristics treated with GH alone served to better evaluate the efficacy of addition of GnRHa. At the start of combined treatment, the chronological age of the girls (CA; mean +/- SD) was 10.2 +/- 0.9 yr, bone age (BA) was 10.6 +/- 1.9 yr, height SD score for BA was - 1.81 +/- 0.8, PAH was 146.3 +/- 5.0 cm. PAH was significantly lower than target height (TH 152.7 +/- 3.6 cm; P < 0.005). GH was given at a dose of 0.3 mg/kg x week, sc, 6 days weekly, and GnRHa (depot-triptorelin) was given at a dose of 100 microg/kg every 21 days, im. The 12 girls were treated with GH alone at the same dose; at the start of therapy their CA was 10.7 +/- 1.0, BA was 10.1 +/- 1.4 yr, height SD score for BA was - 1.65 +/- 0.8, PAH was 145.6 +/- 4.4 cm, and TH was 155.8 +/- 4.6 cm. Pubertal Tanner stage in both groups was B2P2 or B3P3. LHRH test and pelvic ultrasound showed the beginning of puberty. The GH response to standard provocative tests was 10 g/L or more. The mean period of treatment was 4.6 +/- 1.7 yr in the group treated with GH plus GnRHa and 4.9 +/- 1.4 yr in the group treated with GH alone; both groups discontinued treatment at comparable CA and BA. Adult height was considered to be attained when growth during the preceding year was less than 1 cm, with a BA of over 15 yr. Patients in the group treated with GH plus GnRHa showed an adult height significantly higher (P < 0.001) than the pretreatment PAH (156.3 +/- 5.9 vs. 146.3 +/- 5 cm); the gain in centimeters calculated between pretreatment PAH and adult height was 10 +/- 2.9 cm, and 7 of 12 girls had a gain over 10 cm. Target height was significantly exceeded. Height SD score for BA increased from - 1.81 +/-0.8 to -0.85 +/- 1.0. The GH alone group reached an adult height higher than the pretreatment PAH (151.7 +/- 2.7 vs. 145.6 +/- 4.4 cm); the gain in final height vs. pretreatment PAH was 6.1 +/- 4.4 cm, and 5 of 12 girls did not gain more than 4 cm. TH was even not reached. The height SD score did not significantly change. No adverse effects were observed in either group. All of the girls showed good compliance and were satisfied with the results. Our experience suggests that the combination of GH and GnRHa is significantly more effective in improving adult height than GH alone in girls with idiopathic short stature, early or normal onset of puberty, and low PAH well below the third percentile and TH. As the cost-benefit of such invasive treatment must be seriously considered, further studies are needed due to the small sample of our patients as well as in other studies reported to date.