Return to fertility after extended chemical castration with a GnRH antagonist

Janusz W Kostanski¹ , Ge Jiang² , Bhas A Dani² , Santos B Murty² , Wei Qiu² , Bruce Schrier³ , B C Thanoo³ and Patrick P DeLuca²

¹Pharmaceutical Research Institute, Bristol-Myers Squibb Company, New Brunswick, NJ 08903, USA

²Faculty of Pharmaceutical Sciences, University of Kentucky College of Pharmacy, Lexington, KY 40536, USA

³Oakwood Laboratories, LLC, Oakwood, OH 44146, USA

author email corresponding author email

BMC Cancer 2001, 1:18doi:10.1186/1471-2407-1-18


Published:	29 October 2001

Abstract

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.