Preventive role of exogenous testosterone on cisplatin-induced gonadal toxicity: an experimental placebo-controlled prospective trial.
OBJECTIVE
To test the preventive role of exogenous T on spermatogenesis after cisplatin chemotherapy.


METHODS
Placebo-controlled study.


METHODS
The animal laboratory of a medical university.


METHODS
Eighty-eight male BALB/c mice were divided into three groups; each group was subdivided into four groups.


METHODS
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.


METHODS
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.


RESULTS
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).


CONCLUSIONS
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.
Department of Urology, Comparative Medicine Research Center, Shiraz Nephrology Urology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran. aminsharifi_ar@yahoo.com
Alireza
A
Aminsharifi
Saeed
S
Shakeri
Ali
A
Ariafar
Behnam
B
Moeinjahromi
Prikala V
PV
Kumar
Saeed
S
Karbalaeedoost
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000633:toxicity*; D001284:Atrophy; D002945:Cisplatin / Q000008:administration & dosage / Q000633:toxicity*; D019610:Cytoprotection; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D007273:Injections, Intramuscular; D007274:Injections, Intraperitoneal; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D015990:Placebo Effect; D020011:Protective Agents / Q000008:administration & dosage* / Q000633:toxicity; D013076:Sperm Count; D013091:Spermatogenesis / Q000187:drug effects*; D013737:Testis / Q000187:drug effects* / Q000473:pathology; D013739:Testosterone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000633:toxicity; D013997:Time Factors
D000970:Antineoplastic Agents; D020011:Protective Agents; D013739:Testosterone; C004648:testosterone enanthate; D002945:Cisplatin