Studies utilizing the administration of
GnRH in various
GnRH-deficient models have revealed the critical importance of the dose and mode of delivery of this releasing factor in determining the subsequent pituitary response. Chronic administration of long acting
GnRH agonists (GnRHa), like continuous infusion of high doses of the native
peptide, results in suppression of pituitary
gonadotropin secretion. This selective and reversible suppression of
gonadotropin secretion suggested several therapeutic applications for these analogs, particularly in the treatment of
central precocious puberty (
CPP), a disorder for which the previously available
therapies lacked uniform efficacy and were associated with potential side effects. In our series, 74 children with
CPP have been treated during the last 5 yr with the potent
GnRH agonist, [D-Trp6, Pro9-ethylamide(NEt)]
GnRH. Having selected a dose and route of administration that produced uniform suppression of spontaneous and stimulated pituitary
gonadotropin secretion, GnRHa
therapy resulted in a fall of gonadal sex
steroid levels into the prepubertal range, a halting or regression of secondary sexual development, and a complete cessation of menses. Growth velocity slowed during
therapy, with this slowing more pronounced during prolonged treatment periods and among those patients with more advanced chronological and skeletal ages. Skeletal maturation was retarded to a greater degree than linear growth, with resultant increases in the predictions for adult stature. Moreover, these benefits have been achieved in the absence of significant side effects. Complete reversal of the suppression of gonadarche has followed discontinuation of
therapy; however, patterns of growth and skeletal maturation after discontinuation of GnRHa administration remain to be characterized. Thus, the impact of GnRHa
therapy on final height must await further longitudinal study. The selective nature of GnRHa suppression of gonadarche also permits an investigation of the natural history of adrenarche and its discrete influences upon skeletal growth and maturation. In addition, GnRHa
therapy of
CPP provides a unique opportunity to study the effects of gonadal sex
steroids on GH secretion and
somatomedin-C (Sm-C) generation during sexual maturation. Finally, the detailed characterization of children with
precocious puberty has helped to define more precisely a subset of patients whose precocity occurs in the absence of demonstrable
gonadotropin secretion.(ABSTRACT TRUNCATED AT 400 WORDS)