儿童性早熟药物治疗进展

性早熟包括中枢性性早熟(CPP)和外周性性早熟(PPP)2种.1个月缓释型促性腺激素释放激素类似物(GnRHa)是CPP的标准治疗药物,较长时间缓释型GnRHa的疗效与1个月缓释型相近,而有较好的发展前景;重组人生长激素(rhGH)或氧雄龙不推荐常规用于接受GnRHa治疗的CPP患儿.PPP的治疗要根据性别、病因、药物机制等个体化,确切疗效需要更多中心观察;继发性CPP需联合应用GnRHa.     

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治疗中枢性性早熟远期效果的系统综述

<正>自20世纪80年代以来,以曲普瑞林和亮丙瑞林为代表的促性腺激素释放激素类似物缓释剂(GnRHa)广泛应用于中枢性性早熟(CPP)的治疗,旨在抑制性发育、延缓骨骼成熟和改善最终成年身高[1,2]。目前资料证实,CPP患儿经GnRHa治疗后可获得较好的短期疗效,可有效地抑制性发育进程、延缓骨龄快速进展,并可提高治疗后的预测成人身高。但关于GnRHa的长期疗效,特别是对CPP患儿终身高、生殖功能和代谢等方面的远期影响,资料尚有限。最早开始GnRHa治疗的CPP患者目前已达终身高,部分     

对中枢性(真性)性早熟诊断和治疗的建议

性早熟是儿科常见的发育异常 ,为规范中枢性 (真性 )性早熟的诊断和治疗 ,中华医学会儿科学分会内分泌遗传代谢学组对此进行了专题讨论 ,提出以下建议供参考。一、定义性早熟是指女孩在 8岁前 ,男孩在 9岁前呈现第二性征(见附 )。中枢性性早熟 (CPP)是指由于下丘脑提前分泌促性腺激素释放激素 (GnRH) ,激活了性腺轴 ,使垂体分泌促性腺激素以致性腺发育 ,从而导致的内、外生殖器发育和第二性征呈现。CPP重要特征是以上过程呈进行性直至生殖系统成熟。CPP又称为GnRH依赖性性早熟。二、病因中枢性性早熟病因分两大类 :(1 )中枢神经系统器…     

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。     

生长激素在性早熟治疗中的应用

目前中枢性性早熟 (CPP)治疗首选促性腺激素释放激素类似物 (GnRHa) ,通过抑制垂体—性腺轴 ,使性早熟的症状得到控制 ;同时防止骨骺过早愈合 ,以改善成人身高。但在治疗过程中 ,由于GnRHa的作用 ,使性激素水平降低 ,部分患者生长速率也随之下降 ,甚至低于正常个体的生长速率 ,使其最终身高仍得不到改善 [1 ,2]。因此 ,针对这部分患者我们采用GnRHa联合应用r_hGH治疗 ,取得了良好的效果 ,现报告如下。资料与方法一、对象9例均为女孩 ,入选标准 :①8岁以前出现第二性征 ;②LHRH激发试验呈青春期反应(LH峰值>10mIU/ml,LH峰值/FSH峰…     

促性腺激素释放激素拟似剂与儿童真性性早熟

促性腺激素释放激素拟似剂（GnRHa)是目前治疗儿童性性早熟的首选药物,它通过垂体的降调节作用抑制青春期的提前出现,临床需根据患儿病情确定是否应用及何时应用GnRHa,并监测疗效。GnRHa可有效改善最科身高且无明显不良影响。     

促性腺激素释放激素激动剂治疗女童性早熟的不良反应探析

促性腺激素释放激素激动剂(gonadotropin releasing hormone agonist,GnRHa)是目前临床广泛应用的相对安全的性早熟治疗药物.患儿在停药后可以正常月经来潮、怀孕、生育.GnRHa不会降低青春期后的子宫体积,停药后的黄体生成素、卵泡刺激素及性激素水平可恢复至接近或超过停药前水平.研究提示促性腺激素释放激素拟似物可能会增加罹患雄激素过多症及多囊卵巢综合征的风险,但尚缺乏较高等级的证据.现有的研究不能提供充分证据表明GnRHa对骨矿物质密度有显著和不可逆的负面影响.GnRHa可能具有增加体质量指数(BMI)的不良反应,亦有研究表明GnRHa有助于降低BMI,或不会增加BMI.     

中枢性性早熟对儿童体格及性发育的影响

中枢性性早熟（CPP）是一种青春期发育异常,表现为第二性征提前、骨格成熟和体格提前发育,最终影响儿童的成年身高,甚至可能会产生如恐惧、不安等心理行为问题。目前国际上公认治疗最好的药物为促性腺激素释放激素类似物（GnRHa）,其主要目的是改善儿童的最终成年身高;但与此同时,其对患儿的生长发育也存在一些不良反应。该文就CPP及GnRHa治疗对儿童体格及性发育的影响作一综述,以引起临床医师对此疾病及其安全用药的关注。     

达那唑治疗特发性中枢性性早熟疗效探讨

目前治疗特发性中枢性性早熟(ICPP)的常选药物有促性腺激素释放激素类似物(GnRHa)和炔睾醇(Danazol，达那唑)。GnRHa通过调节降低垂体促性腺激素的分泌，延缓骨骺的成熟，实现年龄对骨龄的追赶而改善终身高，疗效已得到公认。而用达那唑治疗ICPP，在实现身高对骨龄的追赶过程中，生长与成熟的关系、最终能否改善终身高尚存有争议。我们用达那唑治疗ICPP患者，观察其对生长与成熟的影响。     

Hormonal changes during GnRH analogue therapy in children with central precocious puberty

Gonadotropin releasing hormone analogues (GnRHa) have been used for treatment of central precocious puberty (CPP) for more than 15 years. They are generally considered safe although data on potential long-term side effects are scarce. However, GnRHa therapy has profound effects on both the hypothalamopituitary-gonadal axis as well as on growth hormone (GH) secretion. Gonadal activity is increased in children with CPP; during GnRHa therapy secretion of gonadal hormones is suppressed as reflected by measurements of LH, FSH, and estradiol/testosterone. More recently, studies of levels of inhibin A and B as well as markers of androgen action such as SHBG and prostate specific antigen have demonstrated marked suppression of gonadal function possibly to infra-physiological levels. The possible long-term consequences of these observations have yet to be determined. Detailed analyses of the GH-IGF-I axis have revealed a decrease in levels of free, biologically active IGF-I during GnRHa treatment. These findings are in accord with the observed decrease in height velocity in children with CPP under treatment with GnRHa, and may also play a role in the relatively small gain in final height in most patients.     

促性腺激素释放激素类似物治疗对中枢性性早熟和快速进展型青春期患儿成年终身高改善的Meta分析

目的 系统评价促性腺激素释放激素类似物（gonadotropin-releasing hormone analogue,GnRHa）治疗6岁以上中枢性性早熟（central precocious puberty,CPP）和快速进展型青春期（early and fast puberty,EFP）患儿的疗效。 方法 检索PubMed、MEDLINE、Embase、Cochrane Library、中国知网和万方数据库,收集GnRHa治疗CPP和EFP患儿的相关文献,应用Stata 12.0软件对文献资料进行Meta分析。 结果 共纳入10篇文献。总样本量为720例,其中GnRHa治疗组475例,对照组245例。Meta分析结果显示GnRHa治疗组成年终身高［加权均数差（weighted mean difference,WMD）=3.30,95%CI：2.49~4.12,P<0.001］、成年终身高标准差积分（WMD=0.51,95%CI：0.29~0.73,P<0.001）、身高获益（WMD=2.89,95%CI：2.17~3.60,P<0.001）均优于对照组。所有的研究均无严重不良事件报道。 结论 GnRHa治疗对于改善6岁以上CPP和EFP患儿的成年终身高安全有效。 引用格式:     

Optimal therapy of pubertal disorders in precocious/early puberty

GnRHa have been used in the treatment of central precocious puberty (CPP) for a decade and some final results of this therapy are now available. Treatment preserves height potential in younger patients and a complete recovery of the hypothalamic-pituitary-gonadal axis occurs at the end of treatment. However, some aspects of the management of CPP are still debated. Probably the age limits between normal and precocious puberty have to be lowered, and new diagnostic tools will modify and simplify diagnostic criteria. The possibility of progression of premature thelarche into precocious puberty, the pathogenesis of organic and idiopathic precocious puberty, the criteria for decision to treat and to stop treatment and the utility of an association with GH treatment will be better understood in the future. Follow-up of patients after stopping therapy includes frequency and characteristics of menses, the possible higher incidence of polycystic ovary-like syndrome and the correct achievement of a normal peak bone mass and body composition. In this review we discuss some of these points, with particular attention to precocious puberty in girls.     

Efficacy of combined treatment with growth hormone and gonadotropin releasing hormone analogue in children with poor prognosis of adult height

OBJECTIVE: This study was conducted to study the role of combination therapy of growth hormone and Gonadotropin-releasing hormone (GnRH) analogues in girls with idiopathic central precocious puberty (CPP) or idiopathic short stature (ISS). METHODS: Five girls with CPP (median age 9.1 y, pubertal stage 2-3) (3 of them previously treated with GnRH analogue (GnRHa) for 16.2 +/- 0.3 months) and 8 girls with ISS (median age 11.4 y, pubertal stage 2-3) (previously treated with GH for 10.95 +/- 1.42 months), were treated with recombinant human GH (0.33 mg/kg/week) and GnRHa (3.75 mg/28 days) for 22 months. RESULTS: Height of girls with CPP improved from - 1.3 to - 0.2 SDS and height for BA from - 2.1 to - 0.6 SDS (P = 0.042). Predicted adult height (PAH) improved from - 3.1 to - 0.6 SDS (P = 0.042). In girls with ISS only PAH improved from - 3.0 to - 1.5 SDS (P = 0.025). CONCLUSION: Combined treatment improves height and PAH in CPP. Height in ISS is also improved however not significantly.     

Growth hormone and GnRHa combination therapy in the management of precocious puberty

Growth hormone when used in precocious puberty in combination with Gonadotropin releasing hormone analogue (GnRHa) instead of using GnRHa alone has been shown to improve final height prognosis. We report here a two-year follow-up of three cases of precocious puberty, two of whom were treated with a combination of GH and GnRHa and the third treated with GnRHa alone.     

Gonadotrophin-Releasing Hormone Analogues as Therapeutic Probes in Human Growth and Development: Evidence from Children with Central Precocious Puberty

ABSTRACT. Statural growth and skeletal development were assessed in 87 girls with idiopathic central precocious puberty (CPP) during gonadotrophin-releasing hormone analogue (GnRHa)-induced suppression of gonadarche. Before the start of therapy, mean chronological age (CA) was 6.3 years and mean bone age (BA) was 10.6 years. During up to 6 consecutive years of complete suppression of gonadal sex steroid secretion, the mean height velocity decreased from 10.8 cm/year to prepubertal rates. At each interval height velocity was found to be inversely and negatively correlated with BA such that girls with advanced BAs grew at rates well below prepubertal norms but appropriately for their degree of skeletal maturation. Skeletal maturation similarly slowed during prolonged GnRHa administration (ABA/ACA = 0.6 ± 0.1 over 3 years, mean ± SD, n = 66) and was also negatively correlated with the BA before the start of therapy. Predicted adult height increased progressively during therapy; however, when analysed as changes in height SDS(BA), the impact of treatment was variable and correlated positively with the initial degree of skeletal maturation. The effect of GnRHa therapy on growth in children with CPP requires long-term study and is best analysed by employing a developmental perspective.     

女童全身体脂比率与性早熟的关系

目的 既往研究提示体重指数（BMI）与女童发育年龄有关，但是否与女童全身脂肪比率相关尚不清楚。该研究旨在分析全身脂肪比率与性早熟的关联性。方法 依据中枢性性早熟诊断与治疗共识将2017年7~8月收治的128例性早熟患儿分为中枢性性早熟组（CPP组，87例）和外周性性早熟组（PPP组，41例），同时纳入51例未发育女童作为对照组。利用双能X线吸收测量法检测上肢组织、腿部组织、躯干组织、男性区、女性区和全身组织的脂肪比率，结合研究对象的年龄、BMI、BMI-Z值、骨龄、卵巢体积、激素水平等实验室检查结果，综合分析脂肪比率和性早熟的相关性。结果 与对照组比较，CPP组和PPP组患儿上肢、腿部、躯干、男性区、女性区和全身组织的体脂率参数以及腿部/全身脂肪比和（上肢+腿部）/躯干脂肪比均显著升高（均P < 0.05），而上述所有体脂率和脂肪分布指标在CPP组和PPP组间比较差异均无统计学意义（均P > 0.05）。在性早熟女童中，高体脂率组的黄体生成素（LH）基础值及黄体生成素释放激素（LHRH）激发试验的LH峰值、LH/卵泡刺激素峰值均显著高于低体脂率组，差异均有统计学意义（均P < 0.05）。同时高体脂率组和低体脂率组LH基础值相比于对照组均显著升高（均P < 0.05）。结论 体脂含量的增加可能是诱发女童性早熟的因素，但具体机制尚有待进一步研究。     

Factors influencing final/near-final height in 12 boys with central precocious puberty treated with gonadotrophin-releasing hormone agonists. Italian Study Group of Physiopathology of Puberty

Gonadotrophin-releasing hormone agonists (GnRHa) have been demonstrated as the therapy of choice for central precocious puberty (CPP). Few studies have provided male patients' adult height data. In our multicenter study we evaluated long-term effects of different GnRHa preparations and final/near-final height (FH) in 12 boys with CPP and analyzed the factors influencing FH. Patients' mean chronological age at the time of diagnosis was 7.6 +/- 0.9 yr. Three patients were treated only with triptorelin at a mean dose of 90 microg/kg i.m. every 28 days. Nine patients initially received buserelin (at a mean initial dose of 53.4 microg/kg/day i.n. divided into 3-6 equal doses) or buserelin (at a mean dose of 36.7 microg/kg/day s.c.) and were subsequently switched to triptorelin. The GnRHa therapy was continued for 4.1 +/- 0.6 yr (range 2.9-5.4). The mean predicted adult height increased from 169.9 +/- 4.2 cm at diagnosis to 180.7 +/- 6.0 cm at the end of treatment. Mean FH was 176.1 +/- 6.1 cm (170.1-190.7), corresponding to mean SDS(CA) 0.4 +/- 0.8 (-0.6/2.5), mean SDSBA 0.2 +/- 0.9 (-0.6/2.4) and mean corrected SDS for target height of 0.4 +/- 0.6 (-0.8/1.2). Multiple regression analysis revealed that FH was mainly influenced by target height and height at discontinuation of GnRHa therapy. The present data indicate that GnRHa therapy significantly improves growth prognosis in boys with CPP and fully restores genetic height potential.