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中华妇幼临床医学杂志(电子版) ›› 2019, Vol. 15 ›› Issue (04) : 437 -443. doi: 10.3877/cma.j.issn.1673-5250.2019.04.014

所属专题： 文献；

论著

不同剂量重组人生长激素治疗儿童中枢性性早熟的临床效果
王淼1, 宋小宇1, 高宇1, 李学超1,†()   
  1. 1. 秦皇岛市妇幼保健院儿科　066000
  • 收稿日期:2019-03-08 修回日期:2019-06-04 出版日期:2019-08-01
  • 通信作者: 李学超

Different doses of recombinant human growth hormone in treatment of children with central precocious puberty: clinical effects

Miao Wang1, Xiaoyu Song1, Yu Gao1, Xuechao Li1,†()   

  1. 1. Department of Pediatrics, Maternal & Child Care Center of Qinhuangdao, Qinhuangdao 066000, Shandong Province, China
  • Received:2019-03-08 Revised:2019-06-04 Published:2019-08-01
  • Corresponding author: Xuechao Li
  • About author:
    Corresponding author: Li Xuechao, Email:
  • Supported by:
    Science and Technology Research and Development Plan Project of Qinhuangdao City(201602A210)
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引用本文：

王淼, 宋小宇, 高宇, 李学超. 不同剂量重组人生长激素治疗儿童中枢性性早熟的临床效果[J]. 中华妇幼临床医学杂志(电子版), 2019, 15(04): 437-443.

Miao Wang, Xiaoyu Song, Yu Gao, Xuechao Li. Different doses of recombinant human growth hormone in treatment of children with central precocious puberty: clinical effects[J]. Chinese Journal of Obstetrics & Gynecology and Pediatrics(Electronic Edition), 2019, 15(04): 437-443.

目的

探讨不同剂量重组人生长激素(rhGH)治疗儿童中枢性性早熟(CPP)的疗效。

方法

选择2016年3月至2018年1月，于秦皇岛市妇幼保健院就诊的50例女性CPP患儿为研究对象。按照随机数字表法，将其分为SH组[n＝25，采取0.5 IU/(kg·d)大剂量重组人生长激素(rhGH)单药治疗]与SS组[n＝25，采取0.2 IU/(kg·d)小剂量rhGH单药治疗]。采用重复测量资料的方差分析方法，对2组患儿治疗前及治疗后6、12个月时的骨龄、骨龄差/实际年龄差(ΔBA/ΔCA)、生长速率(GV)、预测成年期身高(PAH)、子宫体积、卵巢体积、促黄体激素(LH)、卵泡刺激素(FSH)水平变化进行统计学比较。采用χ2检验，对2组患儿治疗前及治疗后6、12个月时的乳房发育、阴毛及腋毛生长情况进行统计学比较。本研究遵循的程序符合秦皇岛市妇幼保健院医学伦理委员会制定的批准，经过该伦理委员会批准(批准文号：20160511)，并与受试儿监护人签署临床研究知情同意书。

结果

① 2组患儿治疗前与治疗后6、12个月的骨龄、ΔBA/ΔCA、GV和PAH，经重复测量资料的方差分析结果显示，不同处理措施与测定时间因素间存在交互作用(F处理×时间＝6.958、7.087、6.996、6.560，P＝0.003、0.001、0.001、0.008)；进一步固定处理措施因素进行分析的结果显示，SH组、SS组患儿治疗前及治疗后6、12个月的骨龄、ΔBA/ΔCA、GV和PAH分别进行组内总体比较，差异均有统计学意义(SH组：F＝9.342、8.209、8.082、8.976，P＝0.013、0.015、0.016、0.014；SS组：F＝8.114、8.005、7.880、8.112，P＝0.015、0.016、0.017、0.015)。SH组、SS组患儿治疗后12个月的骨龄、PAH，均较组内治疗前显著增加，ΔBA/ΔCA、GV均较组内治疗前显著降低，并且差异均有统计学意义(SH组：t＝3.152、P＝0.014，t＝2.713、P<0.001，t＝1.223、P＝0.021，t＝3.759、P＝0.016；SS组：t＝2.169、P＝0.024，t＝3.425、P<0.001，t＝2.855、P＝0.027，t＝4.683、P＝0.012)。②2组患儿治疗前、后不同时间点的子宫体积、卵巢体积、LH、FSH水平，经重复测量资料的方差分析结果显示：不同处理措施与测定时间因素间存在交互作用(F处理×时间＝6.408、7.119、6.417、6.422，P＝0.023、0.001、0.021、0.015)；进一步固定处理措施因素进行分析的结果显示，SH组、SS组患儿治疗前及治疗后6、12个月的上述各指标分别进行组内总体比较，差异均有统计学意义(SS组：F＝9.114、8.127、8.045、8.528，P＝0.014、0.016、0.017、0.015；SS组：F＝8.561、8.140、8.392、8.007，P＝0.016、0.017、0.018、0.016)。SH组、SS组患儿治疗后12个月的子宫体积、卵巢体积、LH和FSH水平，均较组内治疗前显著降低，并且差异均有统计学意义(SH组：t＝3.154、P＝0.022，t＝2.668、P＝0.013，t＝5.312、P＝0.036，t＝3.269、P＝0.027；SS组：t＝2.455、P＝0.032，t＝3.648、P＝0.021，t＝2.569、P＝0.016，t＝4.113、P＝0.027)。③2组患儿治疗前及治疗后6、12个月的乳房发育率、阴毛生长率及腋毛生长率分别比较，差异均无统计学意义(P>0.05)。

结论

采取小剂量rhGH单药治疗CPP患儿，可有效延缓患儿GV，降低雌激素分泌水平，控制病情进展，其临床疗效与大剂量rhGH单药治疗疗效相当。

关键词: 青春期，早熟, 重组人生长激素, 身高, 年龄测定，骨骼, 性征, 治疗结果, 儿童
Objective

To investigate clinical effects of different doses of recombinant human growth hormone (rhGH) in treatment of central precocious puberty (CPP) children.

Methods

A total of 50 children with CPP who were admitted into Maternal & Child Care Center of Qinhuangdao from March 2016 to January 2018 were included into this study. They were randomly divided into SH group [n=25, with the monotherapy of high-dose rhGH 0.5 IU/(kg·d)] and SS group [n=25, with the monotherapy of low-dose rhGH 0.2 IU/(kg·d)]. Analysis of variance of repeated measurement data method was used to analyze the bone age, bone age difference/actual age difference (ΔBA/ΔCA), growth velocity (GV), predicted adult height (PAH), uterine volume, ovarian volume, luteinizing hormone (LH), follicle stimulating hormone (FSH) levels before treatment and 6, 12 months after treatment between two groups. Chi-square test was employed to analyze the rates of breast development, pubes and axillary hair growth before treatment and 6, 12 months after treatment between two groups. The procedures followed in this study were in accordance with the standards established by the Committee of Investigation in Human Beings of Maternal & Child Care Center of Qinhuangdao, and this study was approved by the committee (Approval No. 20160511). Informed consent was obtained from each participates′ guardians.

Results

①Analysis of variance of bone age, ΔBA/ΔCA, GV and PAH by repeated measures ANOVA before treatment and 6, 12 months after treatment showed that there were interactive effects between different treatment measures and different measurement time factors (Ftreatment×time=6.958, 7.087, 6.996, 6.560; P=0.003, 0.001, 0.001, 0.008). The results of further analysis by fixing the factor of treatment measures showed that there were significant differences in bone age, ΔBA/ΔCA, GV and PAH before treatment and 6, 12 months after treatment within SH group and SS group, respectively (SH group: F=9.342, 8.209, 8.082, 8.976; P=0.013, 0.015, 0.016, 0.014; SS group: F=8.114, 8.005, 7.880, 8.112; P=0.015, 0.016, 0.017, 0.015). The bone age and PAH at 12 months after treatment of SH group and SS group all were statistically higher than those before treatment within each group, while ΔBA/ΔCA and GV were statistically lower than those before treatment within each group (SH group: t=3.152, P=0.014, t=2.713, P<0.001, t=1.223, P=0.021, t=3.759, P=0.016; SS group: t=2.169, P=0.024, t=3.425, P<0.001, t=2.855, P=0.027, t=4.683, P=0.012). ②The analysis of variance results of repeated measures ANOVA of uterine volume, ovarian volume, LH, FSH levels at different time points of before and after treatment between two groups were as follows. There were interactive effects between different treatment measures and measurement time factors (Ftreatment×time=6.408, 7.119, 6.417, 6.422; P=0.023, 0.001, 0.021, 0.015). The results of further analysis of the above indexes by fixing the factor of treatment measures showed that there were significant differences in uterine volume, ovarian volume, LH, FSH levels before treatment and 6, 12 months after treatment within SH group and SS group, respectively (SH group: F=9.114, 8.127, 8.045, 8.528; P=0.014, 0.016, 0.017, 0.015; SS group: F=8.561, 8.140, 8.392, 8.007; P=0.016, 0.017, 0.018, 0.016). The uterine volume, ovarian volume, LH and FSH levels at 12 months after treatment of SH group and SS group all were statistically lower than those before treatment within each group (SH group: t=3.154, P=0.022, t=2.668, P=0.013, t=5.312, P=0.036, t=3.269, P=0.027; SS group: t=2.455, P=0.032, t=3.648, P=0.021 , t=2.569, P=0.016, t=4.113, P=0.027). ③The rates of breast development, pubic hair growth and axillary hair growth in two groups before treatment and 6, 12 months after treatment were compared respectively, and all the differences were not statistically significant (P>0.05).

Conclusions

The monotherapy of low-dose rhGH in treatment of CPP children can effectively delay GV, reduce estrogen secretion level and control disease progression of CPP children. Its clinical effects are equivalent to that of monotherapy of high-dose rhGH.

Key words: Puberty, precocious, Recombinant human growth hormone, Body height, Age determination by skeleton, Sex characteristics, Treatment outcome, Child
表1 2组CPP患儿治疗前、后不同时间点各生理参数比较(±s)
组别 例数 骨龄(岁) F值 P值 ΔBA/ΔCA F值 P值
治疗前 治疗后6个月 治疗后12个月 治疗前 治疗后6个月 治疗后12个月
SH组 25 10.4±0.8 11.4±0.8 12.8±0.3 9.342 0.013 10.5±1.0 0.9±0.4 0.6±0.0 8.209 0.015
SS组 25 10.2±0.8 11.6±1.0 12.8±1.1 8.114 0.015 10.5±0.9 0.7±0.7 0.5±0.1 8.005 0.016
F处理×时间值 ? 6.958 ? ? 7.087 ? ?
P值 ? 0.003 ? ? 0.001 ? ?
组别 例数 GV(cm/年) F值 P值 PAH(cm) F值 P值
治疗前 治疗后6个月 治疗后12个月 治疗前 治疗后6个月 治疗后12个月
SH组 25 9.4±1.4 7.8±1.3 5.3±1.0 8.082 0.016 149.4±4.1 152.2±3.5 154.2±4.1 8.976 0.014
SS组 25 9.4±1.3 6.6±1.3 5.2±1.2 7.880 0.017 148.3±4.0 153.2±4.1 159.2±4.1 8.112 0.015
F处理×时间值 ? 6.996 ? ? 6.560 ? ?
P值 ? 0.001 ? ? 0.008 ? ?
表2 2组CPP患儿治疗前、后不同时间点的子宫体积、卵巢体积、促黄体激素和卵泡刺激素水平比较(±s)
组别 例数 子宫体积(cm3) F值 P值 卵巢体积(cm3) F值 P值
治疗前 治疗后6个月 治疗后12个月 治疗前 治疗后6个月 治疗后12个月
SH组 25 4.6±1.6 3.5±1.1 2.9±1.0 9.114 0.014 2.3±0.1 1.8±0.4 1.7±0.2 8.127 0.016
SS组 25 4.4±1.6 3.4±1.1 2.7±0.4 8.561 0.016 2.3±1.0 1.9±0.4 1.6±0.3 8.140 0.017
F处理×时间值 ? 6.408 ? ? 7.119 ? ?
P值 ? 0.023 ? ? 0.001 ? ?
组别 例数 LH水平(U/L) F值 P值 FSH水平(U/L) F值 P值
治疗前 治疗后6个月 治疗后12个月 治疗前 治疗后6个月 治疗后12个月
SH组 25 19.7±3.8 15.2±4.3 14.7±2.9 8.045 0.017 5.3±1.8 4.0±1.6 3.2±0.6 8.528 0.015
SS组 25 19.0±8.3 15.4±7.0 13.9±2.4 8.392 0.018 5.4±2.2 4.3±1.4 3.0±1.1 8.007 0.016
F处理×时间值 ? 6.417 ? ? 6.422 ? ?
P值 ? 0.021 ? ? 0.015 ? ?
表3 2组CPP患儿治疗前、后不同时间点第二性征变化情况比较[例数(%)]
组别 例数 乳房发育 阴毛生长 腋毛生长
治疗前 治疗后6个月 治疗后12个月 治疗前 治疗后6个月 治疗后12个月 治疗前 治疗后6个月 治疗后12个月
SH组 25 23(92.0) 14(56.0) 9(36.0) 25(100.0) 15(60.0) 10(40.0) 22(88.0) 13(52.0) 8(32.0)
SS组 25 25(100.0) 13(52.0) 9(36.0) 25(100.0) 13(52.0) 9(36.0) 21(84.0) 10(40.0) 8(32.0)
χ2值 ? 0.951 1.390 0.932 0.000 1.296 0.986 1.188 1.303 0.931
P值 ? 0.452 0.489 0.508 1.000 0.501 0.443 0.503 0.561 0.509
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