Carel Jean-Claude, Blumberg Joëlle, Seymour Christine, Adamsbaum Catherine, Lahlou Najiba
Department of Pediatric Endocrinology and INSERM U561, Groupe Hospitalier Cochin-Saint Vincent de Paul and Faculté Cochin-Université Paris V, 75014 Paris, France.
Eur J Endocrinol. 2006 Jan;154(1):119-24. doi: 10.1530/eje.1.02056.
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.
This was a multicenter, open-label, 12 month trial conducted in 64 CPP children (54 girls and 10 boys), treated quarterly.
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 > or = 7 IU/l, advanced bone age > 1 year, enlarged uterus (> or = 36 mm) and testosterone level > or = 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.
GnRH-stimulated peak LH < or = 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.
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.
长效促性腺激素释放激素(GnRH)激动剂常用于治疗中枢性性早熟(CPP)。目前用于成人适应症的曲普瑞林11.25mg 3个月长效剂型,此前尚未在CPP中进行评估。
这是一项在64名CPP儿童(54名女孩和10名男孩)中进行的多中心、开放标签、为期12个月的试验,每季度治疗一次。
纳入8岁(女孩)或9岁(男孩)之前出现青春期发育临床症状、促黄体生成素(LH)对GnRH的青春期反应>或=7IU/L、骨龄超前>1岁、子宫增大(>或=36mm)以及睾酮水平>或=0.5ng/ml(男孩)的儿童。在第3、6和12个月时,根据血清LH、卵泡刺激素(FSH)、雌二醇或睾酮以及青春期体征来评估促性腺激素激活的抑制情况。
分别在第3、6和12个月时,62名儿童中有53名(85%)、62名中有60名(97%)以及59名中有56名(95%)达到了主要疗效标准,即GnRH刺激的LH峰值<或=3IU/L。血清FSH和性类固醇也显著降低,而大多数患者的青春期发育出现倒退。从第3个月到第12个月,曲普瑞林的平均残留水平保持稳定。曲普瑞林3个月长效剂型耐受性良好。仅1例出现严重注射疼痛。5名女孩经历了轻度至中度或严重(1名女孩)撤退性出血。
曲普瑞林3个月长效剂型可有效抑制CPP儿童的垂体-性腺轴和青春期发育。与每月一次的长效剂型相比,这种制剂可使每年所需的肌肉注射次数减少两倍。