环磷酰胺和雷公藤多苷对儿童性腺的远期影响

目的观察口服雷公藤多苷（GTW）和（或）静脉应用环磷酰胺（CTX）对儿童性腺的远期影响。方法回顾性收集1986年1月至2005年3月于首都儿科研究所附属儿童医院住院予GTW口服和（或）CTX静脉冲击治疗的原发性肾病综合征和过敏性紫癜肾炎患儿的资料,对停药后5年以上的患儿进行随访,内容包括开始用药时年龄,用药情况（累积剂量和疗程）,随访时年龄,随访时停药时间,婚育史,男性进行精液检测,女性随访乳房发育、初潮时间和月经史。结果符合纳入标准患儿136例,共随访到47例,其中男性21例,女性26例。①男性随访结果：单独应用GTW者12例,开始用药年龄7～14岁,累积剂量51～174mg·kg^-1,随访时停药9～17年,其中6例已婚育,子女均体健;2例女方有怀孕史;4例未婚者行精液检测示异常精子轻度升高1例,精子活动力略下降2例。单独应用CTX者6例,开始用药年龄3～14岁,累积剂量55～72mg·kg^-1,随访时停药6～17年,其中2例女方均有怀孕史;余4例行精液检测示异常精子轻度升高并精子活动力轻度下降1例。先后应用GTW和CTX者3例,应用间隔时间1d至7个月,精液检测示精子数量减少、精子活动率下降、异常精子升高或活动力下降2例。②女性随访结果：单独应用GTW者19例,开始用药年龄7～14岁,累积剂量36～190mg·kg^-1,随访时停药5～20年;单独应用CTX者6例,开始用药年龄12～15岁,累积剂量32～213mg·kg^-1,随访时停药5～9年;先后应用GTW和CTX者1例,应用间隔时间1年,累积剂量分别为87和160mg·kg^-1,随访时分别停药8和7年。已育者的子女均体健,未婚者月经和乳房发育均正常。结论单独口服GTW或CTX静脉冲击治疗累积量较低时可能对男性性腺的损害较轻,对女性生育、月经和乳房发育未见影响。GTW及CTX连续应用者,应用间隔时间较短可能对男性产生显著的性腺损害,应避免短期内连续应用GTW和CTX。

Long-term effects of cyclophosphamide and multiglycosides of tripterygium wilfordii on gonads in children

Objective To observe the influence of oral multiglycosides administration of tripterygium wilfordi（GTW） and intravenous cyclophosphamide（CTX） on gonads in children with primary nephrotic syndrome and anaphylactoid purpura nephritis.Methods Children who were with steroid resistant or dependant,frequently relapse primary nephrotic syndrome or anaphylactoid purpura nephritis and received oral GTW and/or intravenous CTX treatment in Children＇s Hospital of Capital Institute of Pediatrics during 1986 to 2005 were recruited and followed up for 5 to 17 years after stopping treatment with GTW and/or CTX.Informations about the marriage,obstetrical history,women＇s menstrual history,the secondary sexual characteristics,and men＇s semen were collected.Results A total of 136 children were included,47 children were followed-up.①Follow-up of 21 male cases showed：twelve cases received only GTW at 7 to 14 years old,with cumulative dose of GTW being 51-174 mg·kg^-1.Among 8 out of 12 treated cases,6 gave birth to healthy children without any developmental abnormabilities.Wives of the rest 2 cases got pregnant but aborted after pregnancy.Semen analysis from 2 of 4 unmarried cases showed slightly decreased motility but normal sperm density and activity rate.Among 6 cases received only CTX at 3 to 14 years old with cumulative dose of 55-72 mg·kg^-1,2 cases were married and their wives had history of pregnancy but aborted,without history of spontaneous abortion;the other 4 cases received semen analysis with normal sperm density and activity rate,one of them with slightly decreased motility.Three cases received GTW first at 4-9 years old with cumulative dose of 170-701 mg·kg^-1 and received CTX at 5-12 years old with cumulative dose of 60-120 mg·kg^-1;semen analysis showed 2 cases＇ results were abnormal,1 with decreased activity and motility（the interval of receving those two drugs was seven months） and the other with decreased density and motility.②Follow-up of 26 female cases showed：nineteen cases received only GTW,aged 7 to 14 years,cumulative dose of GTW was 36-190 mg·kg^-1.In the 19 cases,6 were married with 5 cases giving birth to healthy children and 1 case was without pregnancy not taking contraception measures but with menarche at 14 years old and married for one and a half years;the other 13 cases were unmarried with normal menstrual cycles and secondary sexual characteristics.Six cases received CTX only,aged 12 to 15 years,the cumulative dose was 32-213 mg·kg^-1;all unmarried cases were with normal menstrual cycles and secondary sexual characteristics.One case received GTW and CTX at different time,GTW at 10 years old with cumulative dose of 87 mg·kg^-1 and received CTX at 11 years old with cumulative dose of 160 mg·kg^-1;All unmarried cases were with normal menstrual cycles and secondary sexual characteristics.Conclusions The results of this study suggested that oral administration of GTW or intravenous CTX treatment as single treatment at lower cumulative dose（150 mg·kg^-1） may be less harmful to male＇s gonads.Continuous application of GTW and CTX with short interval may be harmful to gonads.