Three-month sustained-release triptorelin (11.25 mg) in the treatment of central precocious puberty

Abstract

Objective: Depot GnRH agonists are commonly used in the treatment of central precocious puberty (CPP). The triptorelin 11.25 mg 3-month depot, currently used in adult indications, had not previously been evaluated in CPP. Design: This was a multicenter, open-label, 12 month trial conducted in 64 CPP children (54 girls and 10 boys), treated quarterly. Methods: Children with a clinical onset of pubertal development before the age of 8 years (girls) or 9 years (boys), pubertal response of LH to GnRH $ 7 IU/l, advanced bone age . 1 year, enlarged uterus ($36 mm) and testosterone level $0.5 ng/ml (boys), were included. Suppression of gonadotropic activation, as determined from serum LH, FSH, estradiol or testosterone, and pubertal signs were assessed at Months 3, 6 and 12. Results: GnRH-stimulated peak LH #3 IU/l, the main efficacy criterion, was met in 53 out of 62 (85%), 60 out of 62 (97%) and 56 out of 59 (95%) of the children at Months 3, 6 and 12 respectively. Serum FSH and sex steroids were also significantly reduced, while pubertal development regressed in most patients. Mean residual triptorelin levels were stable from Month 3 through to Month 12. The triptorelin 3-month depot was well tolerated. Severe injection pain was experienced in only one instance. Five girls experienced mild-to-moderate or severe (one girl) withdrawal bleeding. Conclusions: The triptorelin 3-month depot efficiently suppresses the pituitary -gonadal axis and pubertal development in children with CPP. This formulation allows a 3-fold reduction, over the once-a-month depot, in the number of i.m. injections required each year.

Urinary Metabolite Markers of Precocious Puberty

“…Correct diagnosis of the etiology of sexual precocity is critical, because treatment of patients with PPP is different from those with CPP, and some PPP can secondarily evolve into CPP (6). Standard treatment of CPP is to suppress the activation of HPGA (7) through periodically using GnRH agonists such as leuprorelin depot (8) and triptorelin depot (9,10). Patients with CPP have to continue receiving this medication until they reach the average age of the onset of puberty.…”

Efficacy of a Monthly Compared to 3-Monthly Depot GnRH Analogue (Goserelin) in the Treatment of Children with Central Precocious Puberty

“…With triptorelin 11.25 mg 3-month depot, Carel et al [4] found GnRH-stimulated peak LH was suppressed (≤3 IU/l) in 85% of the children at 3 months, 97% at 6 months and 95% at 12 months of treatment, and pubertal development regressed in most patients. In children given different doses of leuprolide sequentially (7.5 mg every 4 weeks for a minimum of 24 weeks, 3.75 mg every 4 weeks for 12 weeks and 11.25 mg with assessment after 3 months), Badaru et al [2] noted higher LH and FSH levels with both 3.75 mg and 11.25 mg at 3 months compared with 7.5 mg.…”

“…While such longer-acting preparations potentially provide greater convenience for the child and family, as yet there are limited data on their efficacy compared to the one-month formulation [2,3,4,5,6]. Suppression of gonadotrophin levels in children with CPP has been found to be comparable for the one- and three-month preparations of leuprorelin [2, 3] and triptorelin [4] given for 3–12 months. Other investigators have reported the results of longer duration of treatment with goserelin [5, 6].…”

Avanços na etiologia, no diagnóstico e no tratamento da puberdade precoce central

“…Estudos recentes revelaram a mesma eficácia e segurança dos a-GnRH de uso mensal, trimestral e anual (8,28,(35)(36)(37). O regime terapêutico da PPC com análogos de aplicação trimestral, aprovado no Brasil, permite a redução do número das aplicações anuais, favorecendo a adesão ao tratamento da PPC (8,38).…”