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.     

夜间尿促性腺激素对判断儿童促性腺激素释放激素类似物治疗后下丘脑-垂体-性腺轴功能的价值

目的 探讨免疫化学发光法( ICMA)检测夜间12 h尿促性腺激素对判断儿童促性腺激素释放激素类似物(GnRHa)治疗后下丘脑-垂体-性腺轴(HPGA)功能状态的价值.方法 患儿12例,其中中枢性性早熟4例(女,年龄7.3 ～9.8岁),青春期预测终身高矮小8例(男3例,女5例;年龄8.8～12.3岁).在GnRHa治疗前及治疗3个月后检测其夜间12 h尿黄体生成素(LH)和卵泡刺激素(FSH).结果 GnRHa治疗前后患儿夜间12 h尿液LH/Cr分别为(339.14±264.02) IU·mol -1和( 43.39±36.65) IU·mol-1(t=3.727,P=0.003),FSH/Cr分别为(1841.59±1287.46) IU·mol -1和( 348.20±165.22) IU·mol-1(t =3.968,P=0.002),当尿LH/Cr＞ 56.44 IU·mol-1同时又有FSH/Cr＞ 604.97 IU·mol-1时,其灵敏度及特异性分别为91.7％及100.0％;而仅当FSH/Cr＞ 604.97 IU·mol-1时,诊断HPGA未被抑制状态具有93.8％的灵敏度及85.7％的特异性;仅当LH/Cr＞ 56.44 IU·mol-1时,则其具有91.7％的灵敏度及83.3％的特异性.结论 夜间12 h尿液LH/Cr和FSH/Cr可用来判断GnRHa治疗后HPGA功能状态.     

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）是目前治疗儿童真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可有效改善最终身高且无明显不良影响。     

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     

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…     

NELL2及其在促性腺激素释放激素分泌中的作用

机体的青春发育及生殖过程受下丘脑-垂体-性腺轴的调控.下丘脑促性腺激素释放激素(GnRH)神经元活化导致GnRH分泌增多是青春期启动的触发因素.GnRH神经元功能活动的调节机制非常复杂,有多种因子影响GnRH的分泌.谷氨酸作为最主要的兴奋性神经递质,可以通过多种机制促进GnRH的分泌.近年来有研究发现NELL2可能通过...     

激素治疗隐睾的机制研究进展

隐睾是儿童时期常见的男性生殖系统畸形,其病因复杂,可能是多种因素共同作用的结果[1].迄今为止,隐睾的发病机制尚未完全阐明,推测可能与下列两大因素有关：①内分泌及分子因素：下丘脑-垂体-性腺轴的损害[2-3];②解剖因素：与胚胎期将睾丸向下牵拉的睾丸引带异常或缺如有关.此外,还与患者所处的环境以及其自身基因有关[4].由于睾丸未及时下降,导致隐睾患者睾丸生殖细胞结构功能异常,甚至可能发生恶变[5],睾丸易出现扭转、易受外伤.     

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。     

绒毛膜促性腺激素对双侧隐睾大鼠睾丸生殖细胞凋亡的影响

目的探讨绒毛膜促性腺激素(HCG)对双侧隐睾生殖细胞凋亡的影响。方法SD雄性幼鼠于日龄22d制备双侧隐睾模型(模型组)后开始隔日肌注HCG20U,共7次。假手术组作为对照。日龄35、60d时处死取睾丸,采用生物素-dUTP/酶标亲和素(TUNEL)法检测生殖细胞凋亡情况。结果模型组双侧隐睾睾丸凋亡指数(AI)高于假手术组。35d假手术HCG治疗组AI高于假手术HCG未治疗组(P<0.05)。60d各HCG治疗组睾丸的AI高于相应HCG未治疗组,组间比较无显著差异(P>0.05)。结论隐睾时睾丸生殖细胞凋亡增加;HCG可增加生殖细胞的凋亡。     

GONADOTROPIN-RELEASING HORMONE (LH-RH) AND HUMAN CHORIONIC GONADOTROPIN IN THE TREATMENT OF TWO BOYS WITH HYPOGONADOTROPHIC HYPOGONADISM

Abstract. Two brothers, 16 and 14 years of age, with hypogonadotrophic hypogonadism and anosmia were treated with subcutaneous injections of 200μg gonadotropin-releasing hormone at 8-hour intervals for 4 weeks. Serum FSH increased to the range of normal adult men, but serum LH and serum testosterone showed little change and no clinical signs of pubertal development occurred. Thereafter the 2 patients were given HCG for 11 months and a combination of HCG and HMG for a further 3 months. In response to this treatment, the serum testosterone levels increased to the range of normal adult men and a marked development of the secondary sex characteristics was seen.     

Garment Therapy does not Improve Function in Children with Cerebral Palsy: A Systematic Review

Aims: To conduct a systematic review asking, does garment therapy improve motor function in children with cerebral palsy? Methods: A systematic review with meta-analysis was conducted to review the literature. Inclusion criteria involved the wearing of therapy suits/garments in children with cerebral palsy. The primary outcome of interest was movement related function and secondary outcomes included impairment, participation, parental satisfaction and adverse outcomes of garment wear. Results: 14 studies with 234 participants were included, of which 5 studies were included for meta-analysis. Garment therapy showed a nonsignificant effect on post-intervention function as measured by the Gross Motor Function Measure when compared to controls (MD = ?1.9; 95% CI = ?6.84, 3.05). Nonsignificant improvements in function were seen long-term (MD = ?3.13; 95% CI = ?7.57, 1.31). Garment therapy showed a significant improvement in proximal kinematics (MD = ?5.02; 95% CI = ?7.28, ?2.76), however significant improvements were not demonstrated in distal kinematics (MD = ?0.79; 95% CI = ?3.08, 1.49). Conclusions: This review suggests garment therapy does not improve function in children with cerebral palsy. While garment therapy was shown to improve proximal stability, this benefit must be considered functionally and consider difficulties associated with garment use.     

Combined Treatment with Gonadotropin-releasing Hormone Analog and Anabolic Steroid Hormone Increased Pubertal Height Gain and Adult Height in Boys with Early Puberty for Height

Twenty-one boys with a height of 135 cm or less at onset of puberty were treated with a combination of GnRH analog and anabolic steroid hormone, and their pubertal height gain and adult height were compared with those of untreated 29 boys who enter puberty below 135 cm. The mean age at the start of treatment with a GnRH analog, leuprorelin acetate depot (Leuplin^®) was 12.3 yr, a mean of 1.3 yr after the onset of puberty, and GnRH analog was administered every 3 to 5 wk thereafter for a mean duration of 4.1 yr. The anabolic steroid hormone was started approximately 1 yr after initiation of treatment with the GnRH analog. The mean pubertal height gain from onset of puberty till adult height was significantly greater in the combination treatment group (33.9 cm) than in the untreated group (26.4 cm) (p<0.0001). The mean adult height was significantly greater in the combination treatment group (164.3 cm) than in the untreated group (156.9 cm) (p<0.0001). The percentage of subjects with an adult height of 160 cm or taller was 90.5% (19/21) in the combination treatment group, and it was 13.8% (4/29) in the untreated group (p<0.0001). Since growth of the penis and pubic hair is promoted by the anabolic steroid hormone, no psychosocial problems arose because of delayed puberty. No clinically significant adverse events appeared. Combined treatment with GnRH analog and anabolic steroid hormone significantly increased height gain during puberty and adult height in boys who entered puberty with a short stature, since the period until epiphyseal closure was extended due to deceleration of the bone age maturation by administration of the GnRH analog and the growth rate at this time was maintained by the anabolic steroid hormone.     

促性腺激素释放激素类似物激发试验尿检法对儿童促性腺激素释放激素类似物疗效的判断价值

目的 探讨促性腺激素释放激素类似物(GnRHa)激发试验时免疫化学发光分析法(ICMA)检测的无创性尿促性腺激素(UGn)可否用于儿童GnRHa的疗效判断.方法 患儿23例(男4例,女19例).中枢性性早熟17例(均为女童),予GnRHa治疗.青春期预测终身高矮小6例(男4例,女2例),予GnRHa联合生长激素治疗.在治疗前和治疗3个月均行GnRHa激发试验,留激发试验0～3.5 h尿,其中18例留取了激发试验前1d同一时段的日间自发性尿,应用ICMA检测促黄体生成素(LH)和卵泡刺激素(FSH).结果 1.治疗前后GnRHa激发试验时UGn显著性检验:治疗前后的尿促黄体生成素(ULH)水平分别为(1.27±1.63) IU和(0.07±0.06) IU,尿卵泡刺激素(UFSH)水平分别为(6.38±3.85)IU和(0.54±0.30) IU.2.GnRHa激发试验时血清Gn峰值和UGn对GnRHa疗效评估:当血清LH峰值(PLH)和FSH峰值(PFSH)分别≤2.30IU·L-1和2.39 IU·L-时,其判断疗效的灵敏度分别为95.45％和100％,特异度均为100％;当ULH水平和UFSH水平分别≤0.083 IU和1.089 IU时,其灵敏度分别为90.91％和100％,特异度均为100％.3.GnRHa激发试验时血清Gn和UGn分别与其激发试验前的比值对GnRHa疗效评估:当血清PLH/日间自发性血清LH、血清PFSH/日间自发性血清FSH分别≤5.40和2.16时,其灵敏度和特异度均为100％;当其激发试验时ULH水平/日间自发性ULH水平、激发试验时UFSH水平/日间自发性UFSH水平分别≤6.076和2.480时,其灵敏度和特异度也均达100％.结论 GnRHa激发试验时ICMA检测的无创性3.5 h UGn水平、激发试验时3.5 h UGn水平/日间自发性UGn水平指标可能对儿童GnRHa疗效具有判断价值,其中UFSH水平及其与日间自发性UFSH水平比值指标价值可能更大.     

Growth Hormone Secretion and Growth Hormone Treatment in Children with Intrauterine Growth Retardation

Albertsson-Wikland, K. (Departments of Paediatrics II and Physiology, University of Gothenburg, Gothenburg, Sweden). Growth hormone secretion and growth hormone treatment in children with intrauterine growth retardation. Acta Paediatr Scand [Suppl] 349: 35, 1989.
Few children with intrauterine growth retardation (IUGR) fail to show catch-up growth during the first year of life. There may he many reasons for this, ranging from disturbances of hormone production to hormonal unresponsiveness of target cells. This report presents preliminary data on growth hormone (GH) secretion and responses to GH treatment in 16 children with IUGR and poor catch-up growth, six of whom had Silver-Russell stigmata. GH secretion was assessed by measurement of the GH response to an arginine-insulin test and determination of spontaneous GH secretion over 24 hours. GH production was heterogeneous hut, more often than expected, children showed both a low response to GH provocation and low spontaneous secretion of GH. Five out of six of the children with Silver-Russell syndrome and seven out of 10 of the children with non-Silver-Russell IUGR gained more than 2 cm in height during 1 year of treatment with GH at a dose of 0.1 IU/kg/day. These results clearly demonstrate that some children with IUGR and poor catch-up growth secrete insufficient amounts of GH, and that many of these very short children show an improvement in growth rate during treatment with physiological doses of GH.     

Growth Response to Human Growth Hormone Treatment in Children with Partial and Total Growth Hormone Deficiency

ABSTRACT. The growth response during the first and second years of human growth hormone (hGH) treatment was studied in 14 prepubertal children with so-called "partial" GH deficiency (peak GH between 8 and 15 mU/1) and compared to 28 prepubertal children with "total" GH deficiency (peak GH less than 8 mU/1). There was no difference in growth acceleration between children with partial and total GH deficiency, when initial covariables were taken into account. In a stepwise multiple regression analysis initial stature, pre-treatment growth velocity and skinfold thickness were shown to be most related to growth response, but after exclusion of 3 children with a genetic form of total GH deficiency and partial TSH deficiency this relationship was lost. GH levels during provocation tests and auxological criteria have a poor predictive value for growth response to hGH therapy.     

Growth Hormone Treatment in Non-Growth Hormone-Deficient Children: Effects of Stopping Treatment

ABSTRACT. Overnight physiological growth hormone (GH) secretion was evaluated in 95 short, prepubertal children (73 boys, 22 girls). All the children were below the 3rd centile for height and achieved CH levels greater than 15 mU/1 following pharmacological stimulation. The mean average GH level was 7.1 mU/l and the mean sum of pulse amplitudes 80.4 mU/l. No relationship was found between age, height or height velocity and any of the parameters of GH secretion. The group was randomized to receive placebo, GH or remain under observation for the first 6 months and then all patients received GH treatment for a further 6 months. Those treated with GH, 0.27 IU/kg (0.1 mg/kg) three times weekly, in the first phase. demonstrated a mean increase in height velocity SDS of 3.24. There was no difference in growth response between the placebo or observation groups. In the second 6-month period. all children received GH according to the same dose regimen: they were then observed for a further 6 months following its discontinuation. In the 6 months following withdrawal of GH, all groups showed a significant fall in height velocity SDS, which returned to pretreatment levels, without demonstrating'catch-down'growth. Repeat sampling of overnight GH secretion within 3 days of discontinuing GH showed normal secretory patterns with a small reduction in mean peak amplitude. These results suggest that short children without classic GH insufficiency respond well to exogenous GH in the short term and return to pretreatment height velocities afterwards. Consequently, it may be possible to increase final adult height in such children by GH treatment.