Use of a Potent, Long Acting Agonist of Gonadotropin-Releasing Hormone in the Treatment of Precocious Puberty*

Abstract

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)

Premature adrenarche: novel lessons from early onset androgen excess

“…In CAH, transition from precocious pseudo-puberty to secondary central precocious puberty has been observed and is thought to be due to the induction of the GNRH pulse generator by persistently increased sex steroids (66). Pubertal progression in central precocious puberty is efficiently halted by GNRH analogues blocking GNRH action (67,68).…”

Role of surgical resection in the treatment of hypothalamic hamartomas causing precocious puberty

“…Therapy using a GnRH agonist is the accepted form of treatment for idiopathic central precocious puberty and has been shown to be effective both in the short term [3] and in the long term. [15] Treatment with the newer sustained-release preparations, Lupron-Depot [6,16] and decapeptyl, [18,20] has resulted in normalization of GV, regression of secondary sexual characteristics, a slowed rate of skeletal maturation, and the attainment of adult height appropriate to genetic potential.…”

Novas perspectivas no tratamento da hiperplasia adrenal congênita

“…O uso do LHRHa retarda a maturação esquelética mais do que diminui a velocidade de crescimento, sugerindo que uma estatura final maior poderia ser alcançada. 8,9,10 A puberdade precoce central pode ser eficazmente suprimida pela administração de um análogo de LHRH (LHRHa). Apesar de o tratamento com LHRHa ser frequentemente acompanhado de uma concomitante desaceleração da velocidade do crescimento, é improvável que tenha um impacto significante na altura final por si só.…”