Combination treatment with growth hormone and gonadotropin-releasing hormone analogs in short normal girls.

To improve final adult height, we treated with growth hormone (0.65 +/- 0.07 (mean +/- SD) IU.kg-1.wk-1) and gonadotropin-releasing hormone analogs (66 +/- 9 micrograms.kg-1 every 28 days) a group of seven short normal girls in early puberty with a chronologic age (CA) of 11.50 +/- 0.95 years, predicted adult height (PAH) lower (0.003 < p < 0.001) than mean target height, and without any endocrine abnormalities. The results were compared with those obtained in a similar group of seven untreated girls considered as control subjects. The mean period of combined therapy was 2.01 +/- 0.52 years; in two subjects treatment is still in progress. The value of height standard deviation score for bone age (BA) improved from -1.69 +/- 0.47 to -1.04 +/- 0.56 (p = 0.001); height age (HA)/BA ratio also increased from 0.83 +/- 0.05 to 0.90 +/- 0.04 (p < 0.01), as did PAH (from 146.8 +/- 4.4 to 152.9 +/- 3.6 cm; p < 0.002). The ratio of gain in HA to gain in BA was 2.08 +/- 0.78. Pubertal stages showed an arrest in five cases and a regression in the other two girls. After administration of gonadotropin-releasing hormone analogs was interrupted, in four of five girls growth hormone was administered alone for a further period of 6 to 18 months to improve their physiologic growth spurt. The present height in five girls is higher than PAH before therapy. In the treated girls the height values for BA, for BA/CA and HA/BA ratios, and for PAH were higher (0.002 < p < 0.04) than those in control subjects. This preliminary study demonstrates that combination therapy with growth hormone and gonadotropin-releasing hormone analogs in short, endocrinologically normal girls may be useful in improving both height prognosis and predicted adult height. Further studies are necessary to reach definitive conclusions regarding the efficacy of this kind of therapy.