Protection against procarbazine-induced testicular damage by GnRH-agonist and antiandrogen treatment in the rat.
Suppression of spermatogenesis in LBNF1 rats by treatment with the GnRH agonist Zoladex combined with the antiandrogen flutamide was evaluated in order to rapidly achieve protection of spermatogenic stem cells against procarbazine with clinically used drugs. Zoladex-flutamide treatment required 3 weeks to suppress the completion of spermatogenesis; only a small degree of suppression was observed with Zoladex alone. The suppression of spermatogenesis was reversible. In rats pretreated for 3 weeks with Zoladex-flutamide, the recovery of spermatogenesis at 9 weeks after a single injection of procarbazine as measured by testis weight, testicular sperm head counts, or a histological end point was significantly better than without hormonal pretreatment. Thus Zoladex-flutamide treatment enhanced the recovery of spermatogenesis from stem spermatogonia after procarbazine treatment in the rat and might be applicable to protect spermatogenesis in patients undergoing chemotherapy for cancer.
Kangasniemi
M
M
Department of Experimental Radiotherapy, University of Texas, M.D. Anderson Cancer Center, Houston 77030, USA.
Wilson
G
G
Huhtaniemi
I
I
Meistrich
M L
ML
D000726:Androgen Antagonists / Q000494:pharmacology*; D000818:Animals; D004338:Drug Combinations; D005485:Flutamide / Q000494:pharmacology; D007987:Gonadotropin-Releasing Hormone / Q000819:agonists*; D017273:Goserelin / Q000494:pharmacology; D006728:Hormones / Q000097:blood; D008297:Male; D011344:Procarbazine / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D051381:Rats; D013091:Spermatogenesis / Q000187:drug effects; D013737:Testis / Q000187:drug effects* / Q000473:pathology*
D000726:Androgen Antagonists; D004338:Drug Combinations; D006728:Hormones; D017273:Goserelin; D007987:Gonadotropin-Releasing Hormone; D011344:Procarbazine; D005485:Flutamide