Preventive role of exogenous testosterone on cisplatin-induced gonadal toxicity: an experimental placebo-controlled prospective trial

被引:11
作者
Aminsharifi, Alireza [1 ]
Shakeri, Saeed [1 ]
Ariafar, Ali [1 ]
Moeinjahromi, Behnam [1 ]
Kumar, Prikala V. [2 ]
Karbalaeedoost, Saeed [3 ]
机构
[1] Shiraz Univ Med Sci, Dept Urol, Comparat Med Res Ctr, Shiraz Nephrol Urol Res Ctr, Shiraz, Iran
[2] Shiraz Univ Med Sci, Dept Pathol, Comparat Med Res Ctr, Shiraz Nephrol Urol Res Ctr, Shiraz, Iran
[3] Shiraz Univ Med Sci, Dept Anat, Comparat Med Res Ctr, Shiraz Nephrol Urol Res Ctr, Shiraz, Iran
关键词
Cisplatin; spermatogenesis; T; mouse; testis; GONADOTROPIN-RELEASING-HORMONE; CHEMOTHERAPEUTIC DRUGS; PROMOTES REGENERATION; RAT SPERMATOGENESIS; TESTICULAR FUNCTION; CANCER; PROTECTION; FERTILITY; ANALOG; DAMAGE;
D O I
10.1016/j.fertnstert.2009.02.028
中图分类号
R71 [妇产科学];
学科分类号
100211 ;
摘要
Objective: To test the preventive role of exogenous T on spermatogenesis after cisplatin chemotherapy. Design: Placebo-controlled study. Setting: The animal laboratory of a medical university. Animal(s): Eighty-eight male BALB/c mice were divided into three groups; each group was subdivided into four groups. Intervention(s): Subgroups a received two or three cycles of cisplatin (2.5 mg/kg for 5 days + 16 days of recovery), subgroups b received the same chemotherapy regimen with adjuvant high-dose T enanthate (5 mg/100 g body weight) starting 1 week before chemotherapy and repeated every 21 days during chemotherapy, subgroups c received only high-dose T enanthate at the same dosage and intervals; subgroups d received a placebo. Main Outcome Measure(s): Testis spermatogenesis function was evaluated after 35 days (short term, group I) or 105 days (long term, groups II and III) of recovery, after the final dose of cisplatin, by histopathology and sperm count. Result(s): Testis tissue destruction and a significant dose-dependent decrease in spermatogenesis were identified in subgroups a. Both recovered partially during long-term recovery. Exogenous high-dose T caused damage to spermatogenesis, which was reversible (subgroups c). Adjuvant treatment with T had no additive long-term effect in animals treated with low-dose cisplatin (two cycles). However, a significant long-term preventive effect of T was seen in animals receiving high-dose cisplatin (three cycles). Conclusion(s): Hormonal intervention with exogenous T during chemotherapy had promising effects on spermatogenesis in mice receiving high-dose chemotherapy (regimens frequently used clinically). It had no additive long-term effects in animals receiving low-dose regimens. (Fertil Steril (R) 2010;93:1388-93. (C)2010 by American Society for Reproductive Medicine.)
引用
收藏
页码:1388 / 1393
页数:6
相关论文
共 21 条
[1]   A postulated role of testosterone for prevention of cisplatin gonadal toxicity [J].
Aminsharifi, A. R. ;
Talaei, T. ;
Kumar, V. ;
Sabayan, B. ;
Samani, S. ;
Mohamadhoseini, E. .
MEDICAL HYPOTHESES, 2007, 68 (03) :525-527
[2]   Drug Insight: recent advances in male hormonal contraception [J].
Amory, JK ;
Page, ST ;
Bremner, WJ .
NATURE CLINICAL PRACTICE ENDOCRINOLOGY & METABOLISM, 2006, 2 (01) :32-41
[3]  
DELIC JI, 1986, CANCER RES, V46, P1909
[4]  
GLODE LM, 1981, LANCET, V1, P1132
[5]   Testicular function following chemotherapy [J].
Howell, SJ ;
Shalet, SM .
HUMAN REPRODUCTION UPDATE, 2001, 7 (04) :363-369
[6]   Fertility after high-dose chemotherapy for testicular cancer [J].
Ishikawa, T ;
Kamidono, S ;
Fujisawa, M .
UROLOGY, 2004, 63 (01) :137-140
[7]   Recognition of cisplatin adducts by cellular proteins [J].
Kartalou, M ;
Essigmann, JM .
MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS, 2001, 478 (1-2) :1-21
[8]   The present and future state of hormonal treatment for male infertility [J].
Liu, PY ;
Handelsman, DJ .
HUMAN REPRODUCTION UPDATE, 2003, 9 (01) :9-23
[9]   The effects of cancer and cancer treatments on male reproductive function [J].
Magelssen, Henriette ;
Brydoy, Marianne ;
Fossa, Sophie D. .
NATURE CLINICAL PRACTICE UROLOGY, 2006, 3 (06) :312-322
[10]  
MEISTRICH ML, 1984, BIOMED PHARMACOTHER, V38, P137