促性腺激素释放激素激动剂在清髓化疗造血干细胞移植的育龄期女性患者中保护卵巢功能的应用研究

Application of gonadotropin-releasing hormone agonist to protect ovarian function in females undergoing myeloablative chemotherapy and hematopoietic stem cell transplantation

目的探讨血液病患者接受清髓化疗造血干细胞移植前应用促性腺激素释放激素激动剂(GnRH-a)的疗效。方法回顾性分析2011年12月至2018年12月就诊于北京大学人民医院妇科门诊的清髓化疗造血干细胞移植术后的40岁以下育龄期女性共311例。在清髓化疗造血干细胞移植前接受GnRH-a治疗107例为治疗组,未接受GnRH-a治疗204例为对照组,比较两组移植后性激素水平、促性腺激素水平、绝经相关症状、月经恢复情况等。结果与对照组比较,治疗组患者移植后绝经相关症状显著降低(62.62%,74.51%;P=0.029),移植后6个月卵泡刺激素(101.72IU/L,123.29IU/L;P=0.001)和雌二醇水平更低(18.53 pmol/L,33.03 pmol/L;P=0.020),而移植后6个月黄体生成素水平、自发月经恢复及医源性卵巢早衰比较,差异无统计学意义(P>0.05)。调整控制疾病类型及清髓化疗前是否接受化疗等混杂因素后进行分层分析后仍未发现统计学意义。结论对于清髓化疗造血干细胞移植的育龄期女性,GnRH-a治疗不能降低其卵巢早衰发生率,但显著降低清髓化疗造血干细胞移植后的卵泡刺激素和雌激素水平,减少围绝经期相关症状,可能具有一定的卵巢保护作用,但仍需进一步研究验证。

Objective The purpose of this study was to investigate the efficacy of GnRH-a treatment before myeloablative hematopoietic stem cell transplantation in patients with hematological diseases.Methods A total of 311 women under 40 years of childbearing age who underwent hematopoietic stem cell transplantation with myeloablative chemotherapy in Peking University People’s Hospital from December 2011 to December 2018 were retrospectively analyzed.107 cases were treated with GnRH-a before myeloablative chemotherapy,and 204 cases were not treated with GnRH-A as the control group.The levels of sex hormones,gonadotropin,menopausal symptoms,and menstrual recovery after transplantation were compared between the two groups.Results Compared with that of the control group,the rate of menopause-related symptoms in the treatment group was significantly lower(62.62%,74.51%,P=0.029).The level of FSH(101.72 IU/L,123.29 IU/L,P=0.001)and E2(18.53 pmol/L,33.03 pmol/L,P=0.020)at the time of six months after transplantation were significantly lower in the treatment group.There was no significant difference in LH level,the rate of spontaneous menstruation recovery,and the rate of iatrogenic premature ovarian failure between the two groups(P>0.05).No statistical significance was found in stratified analysis after adjusting for confounding factors such as the type of disease and whether chemotherapy was received.Conclusion For female patients of childbearing age who received myeloablative hematopoietic stem cell transplantation,GnRH-a treatment may not reduce the incidence of premature ovarian failure.However,the significantly decreased level of gonadotropin and E2 after myeloablative chemotherapy following GnRH-a treatment may reduce menopausal symptoms,suggesting that GnRH-a treatment may have a certain ovarian protective effect.However,these results need further verifications by clinical trials.