© 1992 Oxford University Press
research-article |
Effects of a GnRH Agonist on Fertility following Administration to Prepubertal Male and Female Rats
Drug Safety Evaluation Division, Abbott Laboratories Abbott Park, Illinois 60064
Received July 18, 1991; accepted January 8, 1992
Leuprolide, a GnRH agonist, was administered daily to male and female rats for 90 days. Animals were sexually immature (25 days old) at the outset. Dosages were 20 and 200 µg/kg/day. Five males and five females were euthanized on Day 91. Sex organs were weighed and evaluated for histopathologic changes. These procedures were repeated 140 days later. Following a recovery period lasting 45 days (onset of normal-appearing estrous cycles) in females and 140 days (two spermatogenic cycles) in males, the fertility of these rats was assessed by mating with untreated animals. Treated males gained less weight while treated females gained more weight than controls. Weights of primary and secondary sex organs were reduced below control, but returned to normal following 140 days of recovery. Treated males were fertile and produced normal litters. Reproductive performance of low-dosage (20 µg/kg/day) females was normal 45 days after treatment cessation, but half of the high-dosage (200 µg/ kg/day) females failed to become pregnant. However, reproductive performance of this group compared well with control performance after an additional 6 weeks of recovery. Atrophic changes were noted in male and female sex organs. Following 140 days of recovery, ovaries, uterus, vagina, prostate, and seminal vesicle were normal. Although testes and epididymides showed partial recovery at this time, multifocal or segmental atrophy and mineralization were noted in portions of some seminiferous tubules.