Anti-fertility effects of oral medroxyprogesterone acetate in rabbits

Studies on the anti-fertility effects of medroxyprogesterone acetate (MPA) were conducted in rabbits. The bioavailability of MPA and plasma concentrations of progesterone and luteinizing hormone (LH) after mating were monitored following a single meal containing MPA (1000 mg) in entire does (n = 4); the response to gonadotrophin-releasing hormone (GnRH; 250 ng) was also observed in MPA-treated, ovariectomized does (n = 6). The reproductive tracts of rabbits mated following MPA treatment were examined 28-30 h after mating. Another group of rabbits (n = 4) received a single dose of MPA on Days 1, 10 or 19 after mating or daily for five days from Day 24. After dosage with 1000 mg MPA, plasma concentrations of MPA were detectable for eight days. However, following multiple dosing (10 mg, 5 days) MPA was detectable in the plasma for two days. MPA reduced the rate of ovulation and suppressed the increase in plasma concentrations of progesterone and LH observed after mating for four days, but had no effect on the response to GnRH. When administered late in gestation, MPA caused the death of fetuses. These results demonstrate an inhibitory effect of MPA on ovulation, probably at the hypothalamic level, and impairment of gestation or parturition.