Combined therapy with GnRH analog plus growth hormone in central precocious puberty

GnRH analogues (GnRHa) arrest pubertal development, and slow growth velocit y (GV) and bone maturation, thus improving adult height in central precocio us puberty (CPP). In some patients, however, GV decreases to such an extent that it compromises the improvement in predicted adult height (PAH) and th erefore the addition of GH is suggested. Of 20 patients with idiopathic CPP (treated with GnRHa [depot-triptorelin] at a dose of 100 mu g/kg every 21 days i.m. for at least 2-3 yr) whose GV fell below the 25(th) percentile fo r chronological age (CA), ten received, in addition to the GnRHa, GH at a d ose of 0.3 mg/kg/wk, s.c. 6 days weekly, for 2-4 yr. Ten patients matched f or BA, CA, and duration of GnRHa treatment who showed the same growth patte rn but refused GH treatment, served to evaluate the efficacy of the additio n of GH. No patient showed classical GH deficiency. Both groups discontinue d treatment at a comparable BA (mean +/- SEM): 13.2 +/- 0.2 yr in GnRHa + G H vs 13.0 +/- 0.1 yr in the control group. At the conclusion of the study a ll the patients had achieved adult height. Adult height was considered to b e attained when the growth during the preceding year was less than 1 cm, wi th a BA of over 15 yr. Patients of the group treated with GH + GnRHa showed an adult height significantly higher (p<0.001) than pretreatment PAH (160. 6 +/- 1.3 vs 152.7 +/- 1.7 cm). Height SDS for BA significantly increased f rom -1.5 +/- 0.2 at start of GnRHa to -0.21 +/- 0.2 at adult height (p<0.00 1). Target height was significantly exceeded. The GnRH alone treated group reached an adult height not significantly higher than pretreatment PAH (157 .1 +/- 2.5 vs 155.5 +/- 1.9 cm). Height sos for BA did not change (from -1. 0 +/- 0.3 at start of GnRHa to -0.7 +/- 0.4 at adult height). Target height was just reached but not significantly exceeded. The gain in centimeters o btained calculated between pretreatment PAH and final height was 7.9 +/- 1. 1 cm in patients treated with GH combined with GnRH analogue while in patie nts treated with GnRH analogue alone the gain was just 1.6 cm +/- 1.2 (p=0. 001). Furthermore, no side effects, bone age progression, or ovarian cysts, were observed in GnRHa + GH treated patients. in conclusion, a gain of 7.9 cm in adult height represents a significant improvement which justifies th e addition of GH for 2-3 yr to conventional treatment with GnRH analogues i n patients with central precocious puberty, and with a decrease in growth v elocity so marked as to adult height to below the impair third predicted pe rcentile.