Return to fertility after extended chemical castration with a GnRH antagonist.
BACKGROUND
Antagonistic analogues of GnRH for the treatment of prostate cancer may be used clinically in persons for whom return to fertility after such treatment is important or desirable. The purpose of this study was, therefore, to evaluate the effects of a long term treatment with orntide, a GnRH antagonist, on testosterone levels and fertility in male rats.


METHODS
Two groups of male rats received either 120-day orntide microspheres (8.8 mg orntide/kg/120 days) or vehicle alone (control group). Serum orntide and testosterone levels in both groups were monitored at certain intervals for 9 months from the initiation of treatment. After recovery of normal serum testosterone levels in the treated animals, each rat was housed with two proven breeder, but drug-naive, females.


RESULTS
All mates of treated rats achieved pregnancy as rapidly as the mates of control rats although two of the control rats did not sire a litter with either female and one sired only one litter. The mean size of the litters of treated (12.3 offspring per litter) and control (10.6 offspring per litter) were similar. All offspring were grossly normal morphologically and behaviorally during the time to weaning.


CONCLUSIONS
These results suggest that lack of fertility due to testosterone suppression is reversible after cessation of treatment with this GnRH antagonist.
Kostanski
J W
JW
Pharmaceutical Research Institute, Bristol-Myers Squibb Company, New Brunswick, NJ 08903, USA . janusz.kostanski@bmc.com
Jiang
G
G
Dani
B A
BA
Murty
S B
SB
Qiu
W
W
Schrier
B
B
Thanoo
B C
BC
DeLuca
P P
PP
D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use; D004333:Drug Administration Routes; D005260:Female; D005298:Fertility / Q000187:drug effects*; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors* / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D007248:Infertility, Male / Q000139:chemically induced; D008098:Litter Size / Q000187:drug effects; D008297:Male; D008863:Microspheres; D009919:Orchiectomy / Q000379:methods*; D011471:Prostatic Neoplasms / Q000188:drug therapy; D051381:Rats; D017207:Rats, Sprague-Dawley; D012098:Reproduction / Q000187:drug effects; D013739:Testosterone / Q000097:blood / Q000378:metabolism
D000970:Antineoplastic Agents; C414348:orntide acetate; D007987:Gonadotropin-Releasing Hormone; D013739:Testosterone