Lack of correlation between fertility and sperm numbers in male rats treated with histrelin, a potent LHRH agonist.

Adult male rats were treated daily for up to 8 weeks with histrelin, [(ImBzl)-D-His6, Pro9-NEt]LHRH, to study the antifertility effects of this LHRH agonist. Although serum testosterone concentrations and testicular sperm numbers were significantly decreased by weeks 2 and 4 respectively, a reduction in fertility, as judged by the mean number of fetuses per mated female, was not observed until the sixth week of treatment. Furthermore, the number of spermatozoa in the cauda epididymidis of treated rats did not decrease below initial control levels at any time during the study and full fertility returned within 4 weeks after histrelin treatment was stopped. Thus, the lack of correlation between fertility and testicular and epididymal sperm numbers suggests that the antifertility effects of LHRH agonists are not due solely to reduced sperm numbers, but also result from androgen deficiency.