GnRHa联合rhGH治疗儿童性早熟的效果分析

Analysis of the Effect of GnRHa Combined with rhGH in the Treatment of Precocious Puberty in Children

目的 观察探讨促性腺激素释放激素类似物(gonadotropin releasing hormone analogues,GnRHa)联合重组人生长激素(recombinant human growth hormone,rhGH)治疗儿童性早熟(precious puberty,PP)的效果。方法 方便选取2019年2月—2021年2月厦门大学附属第一医院收治的497例PP女性患儿为观察对象,按治疗方式不同分为GnRHa组(n=246)和GnRHa+rhGH组(n=251),GnRHa组给予GnRHa治疗,GnRHa+rhGH组在GnRHa组基础上联合rhGH治疗,比较两组患儿治疗后的生长发育指标[骨龄、实际身高(Ht)、预测成年身高(PAH)、年生长速度(GV)、身高标准差分值(HtSDS-BA)]、骨代谢指标[N端骨钙素(N-MID)、Ⅰ型胶原羧基端肽交联(β-CTX)、Ⅰ型原胶原氨基端肽(P1NP)]水平、性激素[促卵泡生成素(FSH)、雌二醇(E2)、促黄体生成素(LH)]水平及不良反应发生情况。结果 治疗后,GnRHa+rhGH组骨龄(11.24±0.59)岁、Ht(146.07±3.61)cm、PAH(158.47±4.35)cm、GV(8.82±1.56)cm/年和HtSDS-BA(-0.74±0.26)均明显高于GnRHa组(11.03±0.52)岁、(141.62±4.23)cm、(154.51±4.12)cm、(7.47±1.48)cm/年、(-1.08±0.29),差异有统计学意义(t=4.206、12.634、10.416、9.894、13.768,P<0.05);GnRHa+rhGH组N-MID(57.65±14.04)μg/L、β-CTX(1.49±0.33)μg/L和P1NP(613.27±120.11)μg/L水平均明显低于GnRHa组(68.43±15.27)、(1.78±0.37)、(674.61±132.23)μg/L,差异有统计学意义(t=8.195、9.226、5.415,P<0.05);GnRHa+rhGH组E2(12.92±1.87)IU/L、FSH(2.15±0.49)pg/mL和LH(1.28±0.35)IU/L水平与GnRHa组(13.18±2.04)IU/L、(2.23±0.53)pg/mL、(1.34±0.39)IU/L组间比较,差异无统计学意义(t=1.482、1.748、1.806,P>0.05);GnRHa+rhGH组不良反应总发生率(8.37%)低于GnRHa组(13.01%),差异无统计学意义(χ^(2)=2.809,P>0.05)。结论 GnRHa联合rhGH治疗可明显降低儿童PP骨代谢和性激素水平,并可抑制骨龄成熟,克服生长减速,进而促进身高增长,且安全性较高。

Objective To investigate the effect of gonadotropin-releasing hormone analog(GnRHa) combined with recombinant human growth hormone(rhGH) in the treatment of precocious puberty(PP) in children. Methods 497 female children with PP admitted to the First Hospital of Xiamen University from February 2019 to February 2021 were conveniently selected for observation, and were divided into GnRHa group(n=246) and GnRHa+rhGH group(n=251)according to different treatment modalities. The GnRHa group was treated with GnRHa, and the GnRHa+rhGH group was treated with rhGH on the basis of the GnRHa group. The growth indexes [bone age, actual height(Ht), predicted adult height(PAH), annual growth velocity(GV), height standard deviation score(HtSDS-BA)], bone metabolic indexes [N-terminal osteocalcin(N-MID), type I collagen carboxy-terminal peptide cross-linking(β-CTX), type I procollagen amino-terminal peptide(P1NP)] levels, sex hormones [folliculopoietin(FSH), estradiol(E2), and luteinizing hormone(LH)] levels and the occurrence of adverse effects. Results After treatment, bone age(11.24±0.59) years, Ht(146.07±3.61) cm, PAH(158.47±4.35) cm, GV(8.82±1.56) cm/year and HtSDS-BA(-0.74±0.26) in the GnRHa+rhGH group were higher than those in the GnRHa group(11.03±0.52) years,(141.62±4.23) cm,(154.51±4.12) cm,(7.47±1.48) cm/year,(-1.08±0.29), the difference was statistically significant(t=4.206, 12.634, 10.416, 9.894, 13.768,P<0.05);N-MID(57.65±14.04) μg/L, β-CTX(1.49±0.33) μg/L and P1NP(613.27±120.11) μg/L levels in the GnRHa+rhGH group were significantly lower than those of the GnRHa group(68.43±15.27) μg/L,(1.78±0.37) μg/L,(674.61±132.23) μg/L, the difference was statistically significant(t=8.195, 9.226, 5.415, P<0.05);the levels of E2(12.92±1.87) IU/L, FSH(2.15±0.49) pg/mL and LH(1.28±0.35) IU/L in the GnRHa+rhGH group were compared with those in the GnRHa group(13.18±2.04) IU/L,(2.23±0.53) pg/mL,(1.34±0.39) IU/L groups, the difference was not statistically significant(t=1.482, 1.748, 1.806, P>0.05);the overall incidence of adverse reactions in the GnRHa+rhGH group(8.37%) was lower than that in the GnRHa group(13.01%), and the difference was not statistically significant(χ^(2)=2.809, P>0.05). Conclusion The treatment of GnRHa combined with rhGH can significantly reduce the bone metabolism and sex hormone level of PP in children, inhibit the maturation of bone age, overcome the growth slowdown, and promote the growth of height, with high safety.