每六周皮下注射促性腺激素释放激素类似物缓释剂干预女孩特发性中枢性性早熟

目的　观察延长促性腺激素释放激素类似物 (GnRHa)缓释剂注射间期对特发性中枢性性早熟女孩下丘脑 垂体 性腺轴抑制情况和临床症状改善方面的效果。方法　 4 6例特发性中枢性性早熟女孩随机分为两组 ,A组 :2 6例 ,年龄 (8 3± 1 4 )岁 (6 1～ 11 2 )岁 ,乳房开始发育年龄 (6 6±1 4 )岁 (2～ 8)岁 ,骨龄 (8 9± 1 5 )岁 (6 8～ 11 5 )岁 ;每 6周腹部皮下注射曲普瑞林 3 75mg ,平均剂量为 2 8± 0 6 (1 8～ 4 1) μg/ (kg·d) ;B组 :2 0例 ,年龄 (8 1± 1 3)岁 (5 1～ 10 3)岁 ,乳房开始发育年龄 (7 0± 1 2 )岁 (4～ 8)岁 ,骨龄 (8 9± 1 4 )岁 (6～ 11 5 )岁 ;每 4周肌肉注射曲普瑞林 3 75mg,平均剂量为 4 8± 1 1(3 2～ 7 4 ) μg / (kg·d)。两组均连续用药 1年以上。治疗过程中注意监测以下指标 :性发育情况、身高、体重、生长速率、血性激素的水平、骨龄等。结果　每 6周皮下注射曲普瑞林3 75mg的治疗方案与每 4周肌肉注射普瑞林 3 75mg的治疗方案均能使患儿的第二性征减退、停止发育 ,乳房发育明显受到抑制 ,乳腺回缩或乳腺组织变松软 ;卵巢体积缩小 ,直径大于 0 4cm的卵泡消失 ;促性腺激素分泌减少 ,性激素下降至青春前期水平 ;A、B两组的年生长速率 (cm/年 )分别由治疗前的 6 3±

Clinical study of subcutaneous administration of gonadotropin-releasing hormone agonist every six weeks in girls with idiopathic central precocious puberty

OBJECTIVE: Gonadotropin-releasing hormone agonist (GnRHa) is widely used for the treatment of precocious puberty, but there was no identical regime for the dosage and the interval of administration. The aim of this study was to assess the feasibility of subcutaneous administration of Triptorelin with a prolonged interval (six weeks) for the suppression of pituitary-gonadal axis and clinical signs in girls with idiopathic central precocious puberty (ICPP). METHODS: Forty-six girls with ICPP were enrolled in this trial and were divided into two groups at random, with 26 patients in group A and 20 in group B. There were no significantly differences in chronological age, height, weight, age at clinical onset of puberty and bone age between the two groups before treatment. Triptorelin (Decapeptyl, 3.75 mg) was administered subcutaneously (SC) at 6 weeks intervals in group A or intramuscularly (IM) at 4 weeks intervals in group B. Both forms were given for more than 12 months consecutively. During the period of treatment, the clinical parameters including height, weight, pubertal stage, bone age, uterine volume and ovarian size were documented. The serum levels of luteinizing hormone (LH), follicle stimulating hormone (FSH) and estradiol (E(2)) were monitored using immunoenzymometric assay. RESULTS: Both treatment regimes can completely suppressed the pituitary-gonadal axis. The clinical signs of pubertal development regressed or stabilized in all patients. Breast developments, as reflected by Tanner staging, were regressed. Uterine volume decreased after treatment, however, this decrease did not reach statistical significance. Mean ovarian volume did not change significantly during treatment. The height velocity was significantly decreased from a pretreatment value of 6.3 +/- 1.4 cm/year to 5.8 +/- 1.2 cm/year in group A and 6.7 +/- 1.3 cm/year to 5.4 +/- 1.0 cm/year in group B, respectively. The rate of skeletal maturation was reduced significantly during treatment. The ratio of bone age/chronological age was 1.2 +/- 0.2 or 1.3 +/- 0.3 at the onset of therapy and decreased significantly after the treatment to 0.7 +/- 0.2 or 0.9 +/- 0.1, respectively. The predicted adult height increased significantly and progressively during therapy. The levels of serum LH, FSH and E(2) were returned to the prepubertal condition after 6 - 8 weeks treatment and remained suppressed for the duration of treatment. No significantly side effects of therapy were noted. The most common adverse event during SC treatment was that a non-irritating, 1 cm in diameter mass can be palpated at the site of subcutaneous injection in the abdominal wall of group A patients. It gradually decreased in size, and disappeared after 8 - 12 weeks. Two girls had minimal withdrawal virginal bleeding episodes after the first injection. CONCLUSION: Both IM and SC triptorelin administration were clinically effective. They can induce profound suppression of hypothalamic-pituitary-gonadal axis while stabilizing height velocity, slowing bone maturation and increasing predicted adult height. These results suggest that subcutaneous injection of triptorelin in 6 weeks intervals at a dosage of 3.75 mg was a safe and acceptable regime for ICPP with good efficacy.