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.