促性腺激素释放激素类似物治疗儿童中枢性性早熟短期疗效

为了解短效促性腺激素释放激素类似物(GnRH_a)治疗儿童中枢性性早熟(CPP)的疗效 ,我们总结了近2年来用GnRH_a治疗8例女性CPP患儿的疗效 ,现报告如下。资料与方法一、资料自1997年2月～1999年1月我院小儿内分泌专科门诊收治8例女性CPP患儿 ,发病年龄3～7岁6月 ,平均5岁8月 ;治疗前的生长速度3.5～5.0cm/半年 ,平均4.25cm/半年 ;身高在同年龄、同性别的第90百分位数以上 ;乳房发育按Tanner's标准为Ⅱ～Ⅳ ;阴毛生长6例 ;出现白带4例 ,月经2例。骨龄均大于实际年龄1年以上 ,其中5例大于2个标准差 ;盆腔B超显示子宫和卵巢有不同程度的发…     

促性腺激素释放激素类似物在儿童中枢性性早熟中的应用

中枢性性早熟(CPP)是常见的儿科内分泌疾病,其危害是成年身高减损、性征提前出现及心理问题.3～4周缓释型促性腺激素释放激素类似物(GnRHa)是目前国际上公认的治疗CPP的药物.快速进展型CPP是GnRHa的应用指征.近30 a的应用经验证明,GnRHa能有效抑制骨龄进展,在使线性生长减慢的同时,可有效改善成年身高,不良反应少,对成年后生殖轴功能、骨健康及身体成分等无明显负性影响.     

促性腺激素释放激素类似物在儿童中枢性性早熟中的应用

促性腺激素释放激素(GnRH)依赖性性早熟/中枢性性早熟(GDPP/CPP)是儿科内分泌系统的常见病之一,促性腺激素释放激素类似物(GnRHa)是国际上治疗CPP的主要药物,其通过抑制下丘脑-垂体-性腺轴的活动和性激素分泌,减缓CPP患儿骨龄进展、改善成年身高。在临床实践中,仍需要不断探索GnRHa治疗的获益人群,探讨...     

促性腺激素释放激素类似物联合重组人生长激素对中枢性性早熟女童身高的影响

目的 研究促性腺激素释放激素类似物（GnRHa）与重组人生长激素（rhGh）联合治疗以及GnRHa单用对骨龄≥10岁的特发性中枢性性早熟（ICPP）女童成年身高的改善情况。方法 将6个医学中心确诊为ICPP符合研究条件的80例女童（年龄9.0±0.7岁,骨龄≥10岁）根据治疗方法分为GnRHa与rhGh联合治疗组（31例）及GnRHa单用组（49例）。观察治疗前后的预测成年身高、接近成年身高和身高净获等各项指标的变化。结果 两组在治疗后按骨龄的身高标准差分值均较治疗前有显著改善（P<0.01）,其中GnRHa与rhGh联合治疗组明显优于GnRHa单用组（P<0.01）。联合用药组接近成年身高（157±6 cm vs 157±4 cm）、身高净获（4.68 cm vs 3.89 cm）、停药时预测成年身高（161±5 cm vs 158±5 cm）、接近成年身高与遗传靶身高差值等指标均略高于GnRHa单用组,但差异无统计学意义（均P >0.05）。结论 GnRHa与rhGh联合治疗或GnRHa单用组均能改善骨龄≥10岁ICCP女童的成年身高,但两药联用优势不明显。对ICPP患儿预测成年身高的评估需要慎重,停药时的预测值偏高。     

长效促性腺激素释放激素类似物和甲孕酮治疗对真性性早熟女孩预测身高影响的比较

目的观察促性腺激素释放激素类似物（ＧｎＲＨａ）和甲孕酮用于治疗真性性早熟女孩,对其抑制性发育,减慢骨成熟和生长速度,改善成人期预测身高的作用。方法分别使用两种药物治疗两组特发性真性性早熟女孩各９例,时间６～１２个月,观察治疗前后的身高、性发育情况、骨龄、成人期预测身高等,并进行综合比较。结果两组患儿经治疗后,性发育情况大多数得到抑制。甲孕酮治疗组骨龄年增长为１１岁,身高年增长为７６ｃｍ,成人期预测身高治疗前后无改变。长效ＧｎＲＨａ组骨龄年增长为０２岁,身高年增长为５６ｃｍ,成人期预测身高治疗６个月时增长３１ｃｍ,较治疗前明显改善（Ｐ＜００１）,治疗１年时增长６４ｃｍ,较治疗６个月时更为明显（Ｐ＜００５）。结论长效ＧｎＲＨａ与甲孕酮相比较,除可抑制性发育进程外,还可有效减慢骨成熟和生长速度,最终改善成人期预测身高,治疗时间愈长,效果愈明显     

促性腺激素释放激素类似物治疗儿童真性性早熟10例报告

为观察促性腺激素释放激素类似物 (GnRH_A)治疗儿童性早熟的疗效 ,以GnRH_A每次100μg/kg,每28d应用1次 ,对10例真性性早熟患儿进行治疗。治疗3个月后所有患儿第二性征明显退缩 ;治疗6个月后所有患儿性激素水平下降 ,BA/CA下降 ,预测成年身高[按骨龄预测成年身高 (Bayley_pinneau法 )]由治疗前 (156.4±6.2)cm升至(159.4±7.4)cm(P<0.01)。治疗过程中无明显不良反应。GnRH_A能抑制下丘脑 -垂体 -性腺轴的活动 ,使性激素分泌减少 ,从而使真性性早熟患儿第二性征逐渐退缩 ,骨龄生长减慢 ,改善最终身高 ,而且GnRH_A临床使用安全。     

促性腺激素释放激素类似物对特发性中枢性性早熟女童体重指数影响的长期观察

目的：动态研究促性腺激素释放激素类似物（GnRHa）治疗对特发性中枢性性早熟（ICPP）女童体重指数（BMI）的影响。方法：对2003年1月至2006年1月确诊为ICPP 的134例女童进行随访研究,其中57例给予GnRHa治疗（疗程1.69±0.43年）,测量治疗前、治疗结束时及近成年身高时的身高、体重、骨龄及BMI等,并与未治疗组（77例）比较。结果：（1）GnRHa治疗组在治疗结束时的预测终身高标准差分值（SDS）较治疗前明显升高（P0.05）,且近成年身高SDS明显高于靶身高SDS（P0.05）;近成年身高时的BMI SDS比治疗前和未治疗组明显降低（P<0.01）,但治疗前、治疗结束时及近成年身高时BMI平均值都在±1SD内,处于正常范围。结论：GnRHa对改善ICPP女童终身高有显著疗效;GnRHa治疗后的BMI改变处于正常范围。     

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±     

不同剂量促性腺激素释放激素类似物治疗女童特发性中枢性性早熟的临床观察

目的　观察不同剂量促性腺激素释放激素类似物 (GnRHa)缓释剂治疗特发性中枢性性早熟女童(ICPP)的疗效。方法　以达菲林针 1 0 0 μg/ (2 8d·kg)肌注两次 ,随机改用 40～ 50 μg/ (2 8d·kg) ;与随机改用 80～ 1 0 0 μg/ (2 8d·kg)治疗ICPP女童各 1 0例 ,每例共 1 2次 ,疗程 1年。起始年龄 (8.3± 0 .9)岁 ;观察治疗前后两组性征、身高、骨龄及预测成年身高及性激素、生长激素 (GH)变化。结果　两组治疗后性征均减退 ,性激素水平下降 ,骨龄增长受抑 ;两组预测成年身高改善相似。结论　小剂量达菲林治疗ICPP能有效抑制中枢性性早熟 ,改善患儿成年身高 ,较大剂量具有更实用、经济的优点     

Effect of central precocious puberty and gonadotropin-releasing hormone analogue treatment on peak bone mass and final height in females

To evaluate the effect of central precocious puberty (CPP) and its treatment with gonadotropin-releasing hormone (GnRH) analogues on final height and peak bone mass (PBM), we measured lumbar bone mineral density (BMD) in 23 girls at final height. Patients were distributed in two groups. Group 1: 14 patients with progressive CPP were treated with GnRH analogues; seven patients received buserelin (1600 μg/daily), subsequently switched to depot triptorelin (60 μg/kg/26–28 days); seven patients were treated with depot triptorelin (60 μg/kg/26–28 days); mean age of treatment was 6.2 years (range 2.7–7.8 years); the treatment was discontinued at the mean age of 10.1 years (range 8.7–11.3 years); final height was reached at the mean age 13.4 years (range 12.0–14.9 years). Group 2: 9 patients (mean age 6.5 years, range 4.8–7.7 years) with a slowly progressing variant of CPP were followed without treatment; final height was reached at the mean␣age␣13.6 years (range 12.5–14.8 years). Lumbar BMD (L₂-L₄ by dual energy X-ray␣absorptiometry) was measured in all patients at final height. In group 1, final height␣(158.9 ± 5.4 cm) was significantly greater than the pre-treatment predicted height (153.5 ± 7.2 cm, P < 0.001), but significantly lower than mid-parental height (163.2 ± 6.2 cm, P < 0.005). Subdividing the girls of group 1 according to the bone age at discontinuation of therapy (i.e. ≤11.5 years, n = 5, or ≥12.0 years, n = 9), the former patients had a final height significantly higher than the latter (163.7 ± 3.9 cm vs 156.5 ± 4.6 cm, P < 0.02). In group 2, final height (161.8 ± 4.6 cm) was similar to the pre-treatment predicted height (163.1 ± 6.2 cm, P = NS) and was not significantly different from mid-parental height (161.0 ± 5.9 cm). BMD values (group 1: 1.11 ± 0.14 g/cm², group 2: 1.22 ± 0.08 g/cm²) were not significantly different from those of a control group (1.18 ± 0.10 g/cm²; n = 20, age 16.3–20.5 years) and the patients' mothers (group 1: 1.16 ± 0.07 g/cm², n = 11, age 32.9–45.1 years; group 2: 1.20 ± 0.08 g/cm², n = 7, age 33.5–46.5 years). In group 1, the girls who stopped therapy at a bone age ≤11.5 years had significantly higher BMD (1.22 ± 0.10 g/cm²) compared to those who discontinued therapy at a bone age ≥12.0 years (1.04 ± 0.12 g/cm², P < 0.05). Conclusion In girls with progressive CPP, long-term treatment with GnRH analogues improves final height. A subset of patients with CPP does not require treatment because good statural outcome (slowly progressing variant). In CPP, the abnormal onset of puberty and the long-term GnRH analogue treatment do not impair the achievement of PBM. In GnRH treated patients, the discontinuation of therapy at an appropriate bone age for pubertal onset may improve both final height and PBM. Received: 5 June 1997 / Accepted in revised form 21 November 1997     

下丘脑-垂体-性腺轴抑制程度对中枢性性早熟女童成年预测身高的影响

目的 研究促性腺激素释放激素类似物(GnRHa)治疗过程中下丘脑-垂体-性腺轴(HPGA)抑制程度与中枢性性早熟(CPP)女童成年预测身高(PAH)的关系,以指导临床个体化调节GnRHa 治疗剂量。方法 收集75 例CPP 女童的临床资料,记录GnRHa 治疗的不同时间点身高、骨龄(BA)、子宫卵巢容积及LH、FSH 峰值、E2 水平,计算各时间点PAH,分析PAH 改善(ΔPAH=PAH-靶身高)的情况及其与HPGA 抑制的关系,并采用阈值效应分析寻找ΔPAH 的最佳HPGA 抑制范围。结果 GnRHa 治疗后PAH 较治疗初期有明显改善。ΔPAH 与ΔBA 呈负相关;治疗24 月时ΔPAH 与LH 呈负相关。将子宫容积控制在2.3~3.0 mL 之间,LH 控制在0.8 IU/L 以下,FSH 控制在2.4 IU/L 以下对延缓BA 的增长及改善PAH 有利。结论 GnRHa 治疗能改善CPP 女童的PAH。选择合适的GnRHa 治疗剂量,将子宫容积、LH、FSH 控制在一定范围内,有利于延缓BA 及改善PAH。     

GnRHa治疗中枢性性早熟女童对终身高的影响

目的：观察促性腺激素释放激素类似物（GnRHa）对治疗中枢性性早熟（central precocious puberty,CPP）女童终身高的作用及相关因素。方法：对26例CPP女童应用GnRHa治疗前后预测身高、骨龄的标准差分值［HtSDS(BA)］、终身高、体重指数（BMI）、初潮情况等进行评价,分析它们与终身高的相关性。结果：治疗前预测身高为151.5±5.7 cm;停药时预测身高为158.4±5.2 cm;终身高为158.0±4.0 cm,高于靶身高155.3±4.4 cm (P<0.01)。终身高与初始身高、预测身高、HtSDS(BA)正相关。治疗前BMI为17.1±2.1、治疗后BMI为19.9±3.2,两者呈正相关。停药后平均13.2±6.1个月后初潮,平均初潮年龄为12.2±0.7岁。结论：GnRHa治疗CPP可有效地改善终身高,终身高与治疗前身高及预测身高等密切相关,停药后患儿青春发育与正常儿童相似。［中国当代儿科杂志,2009,11（5）：374-376］     

Final height, gonadal function and bone mineral density of adolescent males with central precocious puberty after therapy with gonadotropin-releasing hormone analogues

Few data are available on the outcome of boys with central precocious puberty (CPP) treated with gonadotropin-releasing hormone (GnRH) analogues. We report on final height, endocrine and exocrine testicular function, and bone mineral density (BMD) in nine males (age 16.7 ± 1.5 years) treated with GnRH analogues from the age 6.0 ± 1.8 years for a mean period of 5.6 ± 2.4 years. The following parameters were evaluated: final height, serum gonadotropin and gonadal steroid levels, spermarche, semen analysis, area and volumetric BMD. Final height (−0.4 ± 1.1 SDS) was significantly higher than pre-treatment predicted adult height (−2.0 ± 1.2 SDS) and not significantly different than midparental height (−0.1 ± 0.8 SDS). Pubertal response of gonadotropins to GnRH test occurred within 1.5 years (mean 0.7 ± 0.4 years) and spermarche (n=7) from 0.7 to 3 years (1.8 ± 0.9 years) after the discontinuation of GnRH analogue therapy. No alteration in semen analysis was found (n=6, sperm count, 10⁶/ml: 52.0 ± 18.7; normal motility (%): 49.5 ± 18.7; atypical morphology (%): 44.5 ± 11.4). Area and volumetric BMD were not reduced (0.2 ± 1.0 SDS and −0.1 ± 0.9 SDS, respectively). Conclusion Long-term treatment with gonadotropin-releasing hormone analogues improves final height in boys with central precocious puberty. Post-therapy data demonstrating normal endocrine and exocrine testicular function support the safety of gonadotropin-releasing hormone analogues on reproductive function. Long-term pharmacological suppression of testicular function in childhood does not impair bone mineral density in late adolescence. Received: 4 May 1999 / Accepted: 30 November 1999     

Effect of combined treatment with gonadotropin releasing hormone analogue and growth hormone in patients with central precocious puberty who had subnormal growth velocity and impaired height prognosis

Growth hormone-insulin-like growth factor-I status and response to growth hormone therapy (0.6 IU/kg/week sc, six times a week for 12 months) were evaluated in 12 girls (chronological age 9.4 ± 1.6 years) suffering from central precocious puberty with growth velocity less than 4 cm/year and no substantial increase or decrease in predicted adult height during gonadotropin releasing hormone (Gn-RH) analogue treatment (D-Trp⁶-LH-RH, 60 μg/kg im/28 days). At baseline, large variations were observed in nocturnal growth hormone (GH) means (pathological values (< 3.6μg/l) 33.3%), stimulated levodopa GH peaks (pathological values (<10.0 μg/I) 28.6%) and serum insulin-like growth factor-I (IGF-I) levels. Neither GH nor IGF-I levels were correlated with growth velocity. During recombinant GH therapy, growth velocity increased significantly (baseline 3.0 ± 0.9 cm/year; 6 months 6.4 ± 1.9cm/year, p < 0.001 versus baseline; 12 months 6.0 ± 1.3cm/year, p < 0.001 versus baseline). There was a significant increase in height SDS for bone age (baseline –1.6 ±0.5 SDS; 12 months -1.04 ± 0.6SDS; p < 0.002) and in predicted adult height (baseline 152.0 ± 3.6cm; 12 months 155.9 ± 3.4cm; p < 0.002). Our results suggest that combined therapy with Gn-RH analogues and recombinant GH can improve growth velocity and predicted adult height in girls with central precocious puberty and impaired height prognosis during Gn-RH analogue treatment.     

GnRHa治疗女性中枢性性早熟疗效及不良反应观察

目的观察促性腺激素释放激素类似物(GnRHa)治疗特发性中枢性性早熟对改善患者终身高的确切疗效,探讨GnRHa治疗的不良反应。方法23例女性特发性中枢性性早熟(ICPP)终止GnRHa治疗后随访(45.0±14.2)个月,观察终身高、月经初潮时间、月经规则程度、体质指数(BMI),比较了G-P图谱、TW3和身高曲线图三种方法预测终身高的精确度。结果GnRHa治疗(24.3±13.1)个月,平均终身高为(160.3±4.2)cm,与靶身高比较,从治疗前预测身高-1.58±2.02SD增加到-0.01±1.53SD。停止治疗后(11.5±5.5)个月出现或复现月经初潮,月经周期均规则。达终身高时BMI为20.81±2.08。停止治疗时G-P图谱和TW3预测值与实际终身高比较差异无统计学意义,均明显高于曲线法的预测值。结论GnRHa治疗ICPP能有效改善终身高,经随访无不良反应。     

Reduction of bone density: An effect of gonadotropin releasing hormone analogue treatment in central precocious puberty

Gonadal steroids drive the significant bone mineral increase that occurs at puberty. Oestrogen deprivation in women results in bone loss. We investigated bone mineralization by single photon absorptiometry in girls with central precocious puberty (n=13, age 3.8–8.5 years) before and during 1 year of treatment with gonadotropin releasing hormone analogue (GnRH-a=longacting D-Trp⁶-GnRH, 60 g i.m. every 28 days). Before GnRH-a therapy, bone mineral density (BMD) was significantly higher in patients than in ten control girls matched for chronological age (patients 0.575±0.097 g/cm², controls 0.433±0.049 g/cm²,P<0.001). Patient BMD was not significantly different from that of ten control girls matched according to patient bone age (0.550±0.046 g/cm²,P=NS). During GnRH-a treatment, pituitary-gonadal axis was suppressed and patient BMD significantly decreased (6 months: –6.0%,P<0.002 vs baseline; 12 months: –8.0%,P<0.001 vs baseline). We conclade that in girls with precocious puberty the activation of gonadal steroid secretion induces an increase in bone mineralization and that oestrogen deprivation by GnRH-a treatment caused a significant decrease in BMD.     

Final height in girls with central precocious puberty: comparison of two different luteinizing hormone-releasing hormone agonist treatments

In order to evaluate the effects of two long-acting luteinizing hormone-releasing hormone agonists on growth, bone maturation and final height in girls with central precocious puberty, we analyzed growth data from 40 girls (15 treated with buserelin intranasal spray (group A), 15 treated with triptorelin depot im every 28 days (group B) and 10 untreated (group C)). Patients in group A started treatment when chronological age (CA) was 7.7 ± 0.9 years, bone age (BA) was 10.2 ± 1.1 years and height was 131.9 ± 5.0 cm. Patients in group B started therapy when CA was 7.6 ± 0.5 years, BA 9.8 ± 1.0 years and height 133.2 ± 7.6 m. The diagnosis of untreated patients (group C) was made when CA was 7.2 ± 0.9 years, BA 9.6 ± 2.2 years and height 130.2 ± 8.6cm. Both luteinizing hormone-releasing hormone agonists appeared to control precocious puberty. Final height in group B (160.6 ± 5.7 cm) was significantly higher than that of group A (153.2 ± 5.0 cm: p < 0.05) and group C (149.6 ± 6.3; p < 0 .01), whereas the difference between groups A and C was not statistically significant. In group B a positive difference was observed between final height (160.6 ± 5.7 cm) and target height (157.6 ± 5.9 cm) (ns); on the contrary, in groups A and C, final height was lower than target height (155.5 ± 5.3 and 156.4 ± 1.3cm, respectively), but only in group C the difference was statistically significant ( p < 0.01). The best results regarding final height obtained by slow-release depot im therapy may be associated with more stable agonist blood levels during treatment.