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

Combined treatment with GH and GnRH analogs (GnRHa) has been proposed to im prove final adult height in true precocious puberty, GH deficiency, and sho rt normal subjects with early or normal timing of puberty with still contro versial results. We treated 12 girls with idiopathic short stature and norm al or early puberty with GH and GnRHa and followed them to adult height; 12 girls comparable for auxological and laboratory characteristics treated wi th 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; m ean +/- 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 signif icantly lower than target height (TH 152.7 +/- 3.6 cm; P < 0.005). GH was g iven at a dose of 0.3 mg/kg.week, sc, 6 days weekly, and GnRHa (depot-tript orelin) was given at a dose of 100 mu g/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 ultraso und showed the beginning of puberty. The GH response to standard provocativ e 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 tr eated with GH alone; both groups discontinued treatment at comparable CA an d BA. Adult height was considered to be attained when growth during the pre ceding year was less than I cm, with a BA of over 15 yr. Patients in the gr oup 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); t he 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 so score for BA increased from -1.81 +/- 0.8 to -0.85 +/- 1.0. The GH alone group reached an adult height higher th an the pretreatment PAH (151.7 +/- 2.7vs. 145.6 +/- 4.4 cm); the gain in fi nal height us. pretreatment PAH was 6.1 +/- 4.4 cm, and 5 of 12 girls did n ot gain more than 4 cm. TH was even not reached. The height so score did no t significantly change. No adverse effects were observed in either group. A ll of the girls showed good compliance and were satisfied with the results. Our experience suggests that the combination of GH and GnRHa is significan tly more effective in improving adult height than GH alone in girls with id iopathic 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 tre atment 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.