亮丙瑞林微球联合生长激素治疗对中枢性性早熟女童性征异常及性激素的影响

Effects of leuprolide microsphere combined with growth hormone on abnormal sexual characteristics and sex hormones in girls with central precocious puberty

目的探讨亮丙瑞林微球联合生长激素治疗对中枢性性早熟(CPP)女童性征异常发育及性激素水平的影响。方法前瞻性选取2019年1月至2020年12月亳州市人民医院收治的120例女童CPP患儿,按随机数字表法分将其为观察组与对照组,每组各60例。对照组给予亮丙瑞林微球治疗,观察组在亮丙瑞林微球的基础上联合使用生长激素治疗,两组均持续治疗1年。比较两组治疗前后生长情况、骨龄、预测成年身高、骨代谢指标[Ⅰ型前胶原氨基端肽(PⅠNP)、β-胶原降解产物(β-CTX)、骨钙素N端中分子片段(N-MID)]、性腺发育、性激素指标水平以及不良反应发生情况。结果两组临床治疗有效率比较,差异无统计学意义(P>0.05)。观察组治疗后身高、生长速度、预测成年身高水平为(134.05±1.46)cm、(6.12±0.64)cm/年、(159.46±2.98)cm,大于对照组[(133.50±1.35)cm、(5.40±0.71)cm/年、(158.11±2.80)cm],差异均有统计学意义(P<0.05);两组治疗后体重指数、骨龄水平比较,差异无统计学意义(P>0.05)。观察组治疗后PⅠNP、N-MID水平为(596.81±90.03)、(14.05±1.88)ng/mL,均低于对照组[(678.75±87.95)、(15.82±1.90)ng/mL],差异均有统计学意义(P<0.05)。两组治疗后子宫、卵巢容积及卵泡直径比较,差异均无统计学意义(P>0.05)。两组治疗后促卵泡成熟素、雌激素、黄体生成素水平比较,差异均无统计学意义(P>0.05)。两组不良反应发生率比较,差异无统计学意义(P>0.05)。结论亮丙瑞林微球治疗联合生长激素治疗可有效降低CPP患儿性激素水平,抑制性腺发育,延缓骨龄,且相较于单纯亮丙瑞林微球治疗,联合用药在不影响患儿骨龄的前提下可有效增加患儿生长速度,改善预测成年身高。

Objective The aim of this study was to explore the effects of leuprolide microsphere combined with growth hormone on abnormal development of sexual characteristics and levels of sex hormones in girls with central precocious puberty(CPP).Methods A total of 120 girls with CPP in Bozhou People's Hospital were prospectively enrolled between January 2019 and December 2020.They were divided into observation group and control group according to random number table,60 cases in each group.The control group was treated with leuprolide microspheres,while observation group was additionally treated with growth hormone.All were continuously treated for 1 year.The growth,bone age,predicted adult height,bone metabolism indexes[type I procollagen amino terminal peptide(PⅠNP),β-collagen degradation products(β-CTX),N-mid osteocalcin(N-MID)],gonadal development,levels of sex hormone indexes and adverse reactions were compared between the two groups before and after treatment.Results There was no significant difference between the two groups in the clinical treatment efficiency(P>0.05).After treatment,height,growth velocity and predicted adult height in observation group were(134.05±1.46)cm,(6.12±0.64)cm/year,(159.46±2.98)cm,which were higher than those in control group[(133.50±1.35)cm,(5.40±0.71)cm/year,(158.11±2.80)cm],the differences were statistically significant(P<0.05);there was no significant difference in body mass index and bone age between the two groups after treatment(P>0.05).After treatment,levels of PⅠNP and N-MID in observation group were(596.81±90.03),(14.05±1.88)ng/mL,which were lower than those in the control group[(678.75±87.95),(15.82±1.90)ng/mL],the differences were statistically significant(P<0.05).After treatment,difference in uterus,ovarian volume and follicle diameter between two groups was not statistically significant(P>0.05).After treatment,there was no significant difference in levels of follicle-stimulating hormone,estrogen and luteinizing hormone between two groups(P>0.05).There was no significant difference between the two groups in incidence of adverse reactions(P>0.05).Conclusion Leuprolide microsphere combined with growth hormone can effectively reduce levels of sex hormones,inhibit gonadal development and delay bone age in CPP children.Compared with leuprolide microsphere alone,combination therapy can effectively accelerate growth rate and improve predicted adult height without affecting bone age.