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效果及安全性

Efficacy and safety of different doses of gonadotropin releasing hormone analogues in the treatment of idiopathic central precocious puberty in girls

目的探讨不同剂量促性腺激素释放激素类似物(GnRHa)治疗女童特发性中枢性性早熟的临床疗效及安全性。方法抽取2019年12月至2021年12月于漯河市第二人民医院治疗的特发性中枢性性早熟女童75例为研究对象。采用随机数字表法将患儿分为低剂量组、中剂量组及高剂量组,每组25例。所有患儿均采用GnRHa药物曲普瑞林治疗,低剂量组、中剂量组及高剂量组的治疗剂量分别为60、80、100μg/kg。比较三组患儿的生长发育情况[体质量、身高、体质指数(BMI)、骨龄、成年期终身高(PAH)]、骨代谢标志物水平[血清Ⅰ型前胶原氨基端肽(P1NP)、β-胶原降解产物(β-CTX)、骨钙素N端中分子片段(N-MID)]、性激素水平[雌二醇(E2)、促卵泡生成激素(FSH)、促黄体生成激素(LH)]及不良反应发生率。结果三组患儿一般临床资料比较差异未见统计学意义(P>0.05)。中剂量组患儿的身高、PAH均高于低剂量组和高剂量组,骨龄及HtSDS-BA低于低剂量组和高剂量组(P<0.05)。治疗后,三组患儿的性激素水平均较治疗前明显下降(P均<0.05),且中剂量组患儿E2、FSH及LH低于低剂量组和高剂量组(P<0.05)。治疗后,三组患儿的骨代谢水平均较治疗前明显下降(P均<0.05);且中剂量组患儿N-MID、β-CTX及P1NP均低于低剂量组和高剂量组(P均<0.05)。低剂量组患儿不良反应发生率为56.00%(14/25),高于中剂量组的48.00%(12/25)和高剂量组的52.00%(13/25),但差异未见统计学意义(P>0.05),各种不良反应经常规对症治疗后,均可缓解。结论GnRHa治疗特发性中枢性性早熟女童疗效显著,且安全性更高,以80μg/kg效果最佳,但临床实际治疗过程中,仍需遵循个体化方案及时调整药物剂量。

Objective To investigate the clinical efficacy and safety of different doses of gonadotropin releasing hormone analogue(GnRHa)in the treatment of idiopathic central precocious puberty in girls.Methods A total of 75 girls with idiopathic central precocious puberty who were treated in Luohe Second People’s Hospital from December 2019 to December 2021 were selected as the study subjects.The children were divided into low dose group,medium dose group and high dose group by random number table method,with 25 cases in each group.All children were treated with the GnRHa(triptorelin).The treatment doses of the low dose group,the middle dose group and the high dose group were 60,80 and 100μg/kg respectively.The growth and development assessed by body mass,height,body mass index(BMI),bone age and adult height at the end of adulthood(PAH),and the level of bone metabolism markers,including serum type I procollagen aminoterminal peptide(P1NP),β-collagen degradation products(β-CTX)and N-terminal middle molecular fragment of osteocalcin(N-MID),levels of sex hormones,including estradiol(E2),follicle-stimulating hormone(FSH)and luteinizing hormone(LH),and the incidence of adverse reactions of the three groups were compared.Results There was no significant difference in general clinical data among the three groups(P>0.05).The height and PAH of children in the medium dose group were higher than those in the low dose group and the high dose group,while bone age and height standard deviation score-bone age were lower than those in the low dose group and the high dose group(P<0.05).After treatment,the levels of sex hormones in the three groups were significantly lower than those before treatment(all P<0.05),and the levels of E2,FSH and LH in the medium dose group were lower than those in the low dose group and the high dose group(P<0.05).After treatment,the bone metabolism level of the three groups was significantly lower than those before treatment(all P<0.05);in addition,the N-MID,β-CTX and P1NP of the medium dose group were lower than those of the low dose group and high dose group(all P<0.05).The incidence of adverse reactions in the low dose group was 56.00%(14/25),higher than that in the medium dose group(48.00%,12/25)and the high dose group(52.00%,13/25),but the difference was not statistically significant(P>0.05).All adverse reactions were alleviated after routine symptomatic treatment.Conclusions GnRHa has a significant effect and higher safety in the treatment of idiopathic central precocious puberty in girls,and 80μg/kg GnRHa with best efficacy.However,in the actual clinical treatment process,it is still necessary to formulate individualized plan and adjust the drug dose in time.