GnRH analog, leuprorelin acetate, promotes regeneration of rat spermatogenesis after severe chemical damage

• Published in: International journal of urology Vol. 8; no. 11; pp. 615 - 622
• Main Authors: Udagawa, Koichi, Ogawa, Takehiko, Watanabe, Takeshi, Yumura, Yasushi, Takeda, Mitsumasa, Hosaka, Masahiko
• Format: Journal Article
• Language: English
• Published: Melbourne, Australia Blackwell Science Pty 01.11.2001
• Subjects: Animals; Antineoplastic Agents, Alkylating - pharmacology; Atrophy; busulfan; Busulfan - pharmacology; chemotherapy; gonadotrophin-releasing hormone analog; Gonadotropin-Releasing Hormone - analogs & derivatives; Leuprolide - pharmacology; leuprorelin; Male; Necrosis; Rats; Rats, Inbred F344; Regeneration; Seminiferous Tubules - drug effects; Seminiferous Tubules - pathology; Seminiferous Tubules - physiopathology; spermatogenesis; Spermatogenesis - drug effects; testicular damage; Testis - drug effects; Testis - pathology
• ISSN: 0919-8172; 1442-2042
• DOI: 10.1046/j.1442-2042.2001.00382.x

Background: Future fertility is a major concern for cancer patients who undergo intensive chemotherapy. There has been controversy about whether hormonal treatments may have protective effects against the severe spermatogenic damage caused by chemotherapy or irradiation. Recently, it has been proposed that gonadotrophin‐releasing hormone (GnRH) analogs administered after testicular damage stimulate the recovery of spermatogenesis. In this study, we have investigated the effects of GnRH agonist, leuprorelin, on the damage to spermatogenesis induced by busulfan. Methods: Fisher rats were treated with busulfan, 25 mg/kg, intraperitoneally. The effects of subcutaneous injections of leuprorelin before or after treatment were evaluated histologically 18 weeks later. Results: The percentage of ‘recovered’ seminiferous tubules was 27.7 ± 12.6% in control rats without leuprorelin and 26.9 ± 10.2% in rats with leuprorelin injected 4 weeks before busulfan. Rats in both groups showed poor recovery of spermatogenesis with an increase of intratesticular fluid. However, rats treated with leuprorelin three times (4 weeks apart) after busulfan showed an improvement of up to 56.5 ± 12.0% (P < 0.05). A focal but massive necrotic lesion in the testis was observed only in this group of rats. Conclusions: The results demonstrated that leuprorelin administered after chemical testicular damage enhanced the recovery of spermatogenesis. At the same time, a possible significant side‐effect of leuprorelin was noted.