Return to fertility after extended chemical castration with a GnRH antagonist

Abstract

BackgroundAntagonistic 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.MethodsTwo 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.ResultsAll 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.ConclusionsThese results suggest that lack of fertility due to testosterone suppression is reversible after cessation of treatment with this GnRH antagonist.

Changes in male rat urinary protein profile during puberty: a pilot study

“…However, apparent increase in overall abundance of urinary proteins by day 107 was clearly concomitant with the several-fold increase in circulating testosterone, if urine evidence at least roughly reflects the situation in its blood plasma source. Nevertheless, the present urine values of ~ 6 ng/ml are close to the 4 ng/ml reported for whole blood by radioimmunoassay in 6 month old Dark Agouti, Wistar and Sprague-Dawley males [23], and ~ 5 ng/ml, also by radioimmunoassay, in adult Sprague-Dawley rat serum [24]. However, we recognise that any further monitoring of circulating testosterone, particularly in pre-pubertal rats, should optimise urine sample collection to avoid any evaporation.…”

Fertility issues in patients with prostate cancer

“…The complete normalization of the sperm count must be viewed against the background that he was medically castrated when RT was started and remained so during the course of RT. In rats, medical castration has been shown to protect the germinative epithelium against the damaging effect of cytostatics and RT [14–16]. This has not been confirmed in patients with testicular cancer and malignant lymphoma.…”

Gonadotropin-releasing hormone antagonists

“…In rats, 8.8 mg/kg subcutaneous injections of orntide formulated in microspheres suppressed testosterone levels below 5 ng/ml for approximately 150 days. Return to fertility was demonstrated at day 269 after injection [34]. Although not published, a Phase I trial demonstrated dose-dependent hormone suppression, with 4 mg of free peptide injected daily for seven days rendering all subjects castrate by day seven; testosterone levels returned to baseline 14 days after the last injection.…”