Current pharmacotherapy of central precocious puberty by GnRH analogs: certainties and uncertainties

Abstract

Monthly GnRH analogs are currently considered the 'gold standard' for the medical treatment of CPP, since a lot of experience is accumulated on their use in children. Differences in long-term outcome (in terms of adult height) are reported and they may be due to differences in selection criteria, treatment monitoring, criteria to stop of therapy, different biological activity of the various drugs and different genetic background of treated patients; altogether, these items remain poorly evaluated. Psychological indications for treatment and long-term psychological outcome of treated children should be better addressed. Comparative trials among the various GnRH analogs are very scarce. New very long-acting GnRH analogs (quarterly or yearly formulations) may improve compliance with therapy, but longer follow-up studies are needed. Medical treatment of CPP should be close to pediatric endocrinologists or tertiary pediatric endocrinology centers with documented experience in this field.

Central Precocious Puberty: Adult Height in Girls Treated with Quarterly or Monthly Gonadotropin-Releasing Hormone Analog Triptorelin

“…It is due to premature reawakening of the hypothalamic gonadotropin-releasing hormone (GnRH) pulse generator with subsequent increase in amplitude and frequency of GnRH pulses, which in turn determines the pubertal secretion pattern of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) by gonadotropin cells in the pituitary [1,2]. The pubertal LH and FSH pattern is responsible for the premature increase in gonadal sex steroid secretion, determining the premature onset of somatic sexual characteristics [1,2]. …”

“…Today, GnRH analogs are the drugs of choice for the medical treatment of CPP [2,3,4,5]. In fact, these drugs are considered able to modify the natural course of CPP, preserving the growth potential in treated children [2,3,4].…”

“…In fact, these drugs are considered able to modify the natural course of CPP, preserving the growth potential in treated children [2,3,4]. GnRH analogs are synthetic analogs of the natural GnRH decapeptide.…”

“…Monthly formulations of the GnRH analog triptorelin have been largely used in children with CPP, and their efficacy in improving adult height (AH) has been demonstrated in long-term follow-up studies [2,3,4,5]. Quarterly formulations of GnRH analogs have been developed [2], and short-term trials showed their efficacy in suppressing the hypothalamic-pituitary-gonadal (HPG) axis in children with CPP [7,8,9,10,11,12,13,14,15,16,17], but long-term follow-up until AH is rarely reported [7].…”

“…Quarterly formulations of GnRH analogs have been developed [2], and short-term trials showed their efficacy in suppressing the hypothalamic-pituitary-gonadal (HPG) axis in children with CPP [7,8,9,10,11,12,13,14,15,16,17], but long-term follow-up until AH is rarely reported [7]. At our knowledge, long-term comparative data of girls treated with monthly or quarterly formulations of the GnRH analog triptorelin are not available.…”