环磷酰胺治疗系统性红斑狼疮导致卵巢功能衰竭的相关因素分析

目的探讨红斑狼疮病人在应用环磷酰眩治疗中出现卵巢功能衰竭的影响因素。方法研究对象为使用环磷酰胺治疗的红斑狼疮病人138例,将其中出现卵巢功能衰竭者46例确定为卵巢衰竭组;按1：2比例选择92例完成环磷酰胺治疗,而未出现卵巢功能损害的病人为对照组。采用病例一对照研究的方法,对各个研究因素采用逐步引入-剔除法,建立Logistic回归模型。结果单因素分析显示,与卵巢衰竭的相关因素包括：开始用环磷酰胺的年龄、红斑狼疮活动指数、雷公藤制剂使用的时间、甲氨蝶呤和婚姻状况。而多因素分析则显示,导致卵巢衰竭的危险因素为：开始用环磷酰胺的年龄、环磷酰胺的累积剂量和雷公藤制剂的疗程。不同年龄组病人的卵巢功能对环磷酰胺累积剂量的耐受性有区别,卵巢衰竭组的年龄明显高于对照组。在卵巢衰竭组,仅4例在20岁以前开始使用环磷酰胺,其累积剂量高达28．8—32．4g;而40—45岁年龄段的11例中,环磷酰胺累积剂量的中位数仅4．8g。结论使用环磷酰胺年龄、环磷酰胺累积剂量、雷公藤制剂使用时间．三者是环磷酰胺治疗红斑狼疮过程中出现卵巢功能衰竭的独立危险因素。

Risk factors of ovarian failure in the patients with systemic lupus erythematosus receiving cyclophosphamide therapy

Objective To determine the risk factors for ovarian failure after cyclophosphamide therapy in the patients with systemic lupus erythematosus (SLE).Methods A case-control study was conducted among 138 female SLE patients, aged 16-45, and treated with cyclophosphamide, 46 of which with premature ovarian failure were included in the case group and 92 of which without menopause after completion of induction therapy with cyclophosphamide were included in the control group. A Logistic regression model was established and step-wise selection was used to analyze different factors, such as age of initiation of therapy, marital history, childbearing history, disease activity index, accumulative dosage of cyclophosphamide, accumulative dosage of azathiopurine, and usage of traditional Chinese medicines etc. Results Univariate analysis showed that age of initiation of cyclophosphamide treatment (OR=1.11, 95%CI=1.06-1.17), SLE activity index(OR=1.11, 95%CI=1.06-1.17), duration of Trypterygium wilfordii treatment (OR=1.26, 95%CI=1.05-1.51), duration of cyclophosphamide treatment (OR=0.16, 95%CI=0.028-0.94), and marital situation were associated with ovarian failure; and multivariate analysis showed that age of initiation of cyclophosphamide treatment(OR=1.24,95% CI=1.14-1.35), cumulative dosage of cyclophosphamide(OR=1.13,95% ,CI=1.05-1.23),and duration of treatment of Trypterygium wilfordii agents(OR=1.36 ,95%CI=1.09-1.69)were significantly associated with premature ovarian failure. Only 4 cases in the case group began to receive cyclophosphamide treatment before the age of 20 and their accumulative cyclophosphamide dosage was 28.8-32.4 g. The median of cumulative dosage of cyclophosphamide was only 4.8 g for the 11 cases aged 40-45 in the case group. Conclusion The risk factors of premature ovarian failure during the induction therapy in SLE patients include age of initiation of cyclophosphamide treatment, cumulative dosage of cyclophosphamide and duration of treatment with leigongteng.