LONG-TERM EFFECT OF GONADOTROPIN-RELEASING-HORMONE AGONIST THERAPY ONFINAL AND NEAR-FINAL HEIGHT IN 26 CHILDREN WITH TRUE PRECOCIOUS PUBERTY TREATED AT A MEDIAN AGE OF LESS-THAN 5 YEARS

We report a long term study on the effectiveness of chronic GnRH agoni st treatment on final or near-final height in 26 patients (20 females and six males) with true precocious puberty (TPP). This study differs from other treatment studies in that the median age at onset of therap y was 4.7 yr for females and 6.2 yr for males, the youngest cohort of treated patients reported to date. We compared patients treated with G nRH agonists who attained final or near-final height with a historical control group of untreated children with TPP (n = 116) matched for me an age of pubertal onset, etiology of TPP (idiopathic or neurogenic), rate of progression, and sex ratio. The current mean height of GnRH ag onist-treated females who began therapy at more than 5 yr of age (157. 6 +/- 6.6 cm) is already significantly greater than the mean final hei ght of untreated females (152.7 +/- 8.6 cm). The current mean predicte d height of the treated females is 164.6 +/- 9.7 cm. The current mean height of females whose treatment was started before 5 yr of age is gr eater (164.1 +/- 7.7 cm) than that of females whose treatment began af ter 5 yr of age (157.6 +/- 6.6 cm). The final height of untreated chil dren whose age of sexual precocity was less than 5 yr at diagnosis is significantly less than that of treated patients who were less than 5 yr when they developed TPP (P = 0.0006). The current mean height of Gn RH agonist-treated males is 166.3 +/- 12.2 cm, and the current mean pr edicted height is 170.8 +/- 11.3 cm. This is in sharp contrast to the mean final height of untreated males (155.6 +/- 7.7 cm). The current p redicted height correlates negatively with the age at initiation of tr eatment and the initial bone age and positively with height so for bon e age in the agonist-treated children. The current mean height deviati on from target height is significantly less in the 20 treated females (-1 SD) than in 93 untreated females (-2.4 SD; P = 0.006). The mean fi nal height deviation from target height in 23 untreated males (-3.7 SD ) is significantly greater than the current height deviation from targ et height in 6 treated males (-1.7 SD; P = 0.03). The salutary effects of long term GnRH agonist therapy on stature are more clear-cut in th e younger treated children. Young untreated children may have the wors t outcome with respect to final height. We suggest that a comparison o f the difference in height between untreated and agonist-treated TPP c hildren, despite its inherent limitations, is a preferable method for determination of the efficacy of therapy on Linear growth than the use of predicted height. The observation that predicted height progressiv ely deteriorates in most untreated patients and the inaccuracy of pred icted height in children with a large discrepancy between bone age and chronological age prompted our use of a historical well matched contr ol group. We conclude that treatment of TPP patients with GnRH agonist s improves final height compared with the height of untreated patients , pretreatment height predictions, or corrected midparental height. Al l of the GnRH agonists that we have used (deslorelin, nafarelin, and l euprolide, including its depot formulation), when given in a dosage su fficient to ensure as complete suppression of gonadal sex steroid secr etion as feasible, were equally effective.