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

doi:10.3877/cma.j.issn.1673-5250.2019.04.014

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 (F_{treatment×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 (F_{treatment×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
组别	例数	治疗前	治疗后6个月	治疗后12个月	F值	P值	治疗前	治疗后6个月	治疗后12个月	F值	P值
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
组别	例数	治疗前	治疗后6个月	治疗后12个月	F值	P值	治疗前	治疗后6个月	治疗后12个月	F值	P值
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
组别	例数	治疗前	治疗后6个月	治疗后12个月	F值	P值	治疗前	治疗后6个月	治疗后12个月	F值	P值
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
组别	例数	治疗前	治疗后6个月	治疗后12个月	F值	P值	治疗前	治疗后6个月	治疗后12个月	F值	P值
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
组别	例数	治疗前	治疗后6个月	治疗后12个月	F值	P值	治疗前	治疗后6个月	治疗后12个月	F值	P值
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
组别	例数	治疗前	治疗后6个月	治疗后12个月	F值	P值	治疗前	治疗后6个月	治疗后12个月	F值	P值
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
组别	例数	治疗前	治疗后6个月	治疗后12个月	F值	P值	治疗前	治疗后6个月	治疗后12个月	F值	P值
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
组别	例数	治疗前	治疗后6个月	治疗后12个月	F值	P值	治疗前	治疗后6个月	治疗后12个月	F值	P值
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
组别	例数	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

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
组别	例数	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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