ADULT HEIGHT IN SHORT NORMAL ADOLESCENT GIRLS TREATED WITH GONADOTROPIN-RELEASING-HORMONE ANALOG AND GROWTH-HORMONE

GnRH analog associated with GH therapy has potential importance for treatment of short stature in subjects without GH deficiency and with a normal onset of puberty. We treated 10 girls with familial short stature with the GnRH analog leuprolide (3.75 mg, im, every 25 days) and GH (0.1 IU/kg . day, sc, 6 days/week). The combined therapies were started simultaneously, and the patients were treated for 28.1 +/- 5.4 (range, 24-36) months. At the onset of treatment, chronological age was 11.6 +/- 1.4 yr, bone age was 10.6 +/- 0.9 yr, height was -2.7 +/- 0.7 SD, predicted height (PH; Bayley-Pinneau score) was 143.2 +/- 3 cm. Target height was 147.6 +/- 5.6 cm. Tanner stage was II-III for breast and genitalia. During treatment, puberty was completely suppressed in all patients. Statistical analysis was performed using Student's t test for paired data. After 12 months of treatment, we observed a significant (P < 0.02) improvement of predicted height (146.2 +/- 3.4 cm). This improvement remained significant (147.6 +/- 3.5; P < 0.001) when treatment was withdrawn. At that time, chronological age was 13.9 +/- 1.2 yr, and bone age was 12.4 +/- 0.7 yr. At the present time (3 +/- 0.97 yr after discontinuation), all of the girls have reached a final height of 144.6 +/- 3 cm (range, 140-149.3 cm). The final height is not significantly different compared with the PH at the beginning of treatment or with target height. These data show that in our patients, combined treatment with GnRH analog-and GH, despite a significant improvement in PH during therapy and upon its withdrawal, does not result in a significant increase in adult stature. Larger and perhaps more prolonged studies in patients of both sexes are required to reach definitive conclusions. Nevertheless, the cost of this treatment in terms of both subject compliance and economic cost should be weighed against the small height gain, if any, that may be achieved.