Gonadal protection from radiation by GnRH antagonist or recombinant human FSH: a controlled trial in a male nonhuman primate (Macaca fascicularis).
Chemotherapy and radiation often damage spermatogenesis irreversibly in oncological patients and various approaches to gonadal protection have been tested with equivocal results. In rats, hormonal protection of spermatogenesis can be achieved by blocking gonadotropin secretion. However, whether the same mechanisms can effect gonadal protection in primates remains questionable. To clarify this Issue we conducted a placebo-controlled trial in a preclinical animal model using macaques (Macaca fascicularis). Twenty adult male monkeys (five in each group) were randomized to receive either recombinant human FSH, GnRH antagonist or saline injections (two groups) for 36 days. On day 29 all groups except one saline-treated control group were exposed to a single testicular irradiation of 4 Gy. Every 2 weeks before, during and after the treatment, ejaculates, body weight, testicular Volume and hormones were analyzed until day 539. In addition, repeated testicular biopsies were performed. Testicular Volume and inhibin B decreased significantly in all irradiated groups compared with baseline and with the non-irradiated control group, followed by a gradual recovery of these parameters, which was, especially at the earlier time points, significantly better in the FSH-treated group compared with both other irradiated groups. Irradiation caused a drastic decrease of sperm parameters in all groups, followed by a partial recovery of sperm parameters, which was significantly slower in the early phases of recovery in the GnRH antagonist group compared with the vehicle group. Testicular histology showed a significant depletion on study day 261 in all irradiated animals. In conclusion, in clear contrast to rodent studies, GnRH antagonist treatment did not provide gonadal protection in this primate model. FSH treatment resulted in slightly better recovery of spermatogenesis, which appears to be of no or only little clinical relevance.
Institute of Reproductive Medicine of the University, Domagkstr. 11, D-48129 Münster, Germany.
A
A
Kamischke
M
M
Kuhlmann
G F
GF
Weinbauer
M
M
Luetjens
C H
CH
Yeung
H L
HL
Kronholz
E
E
Nieschlag
D000704:Analysis of Variance; D000818:Animals; D002452:Cell Count; D043373:Follicle Stimulating Hormone, Human / Q000627:therapeutic use*; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors* / Q000627:therapeutic use*; D007265:Inhibins / Q000378:metabolism; D008252:Macaca fascicularis; D008297:Male; D023421:Models, Animal; D011833:Radiation Injuries, Experimental / Q000378:metabolism / Q000517:prevention & control*; D011878:Radiotherapy / Q000009:adverse effects; D011897:Random Allocation; D013076:Sperm Count; D013737:Testis / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects*; D013739:Testosterone / Q000378:metabolism; D017211:Treatment Failure
D043373:Follicle Stimulating Hormone, Human; C422364:inhibin B; D007987:Gonadotropin-Releasing Hormone; D013739:Testosterone; D007265:Inhibins; C062876:cetrorelix