Investigations into the mechanism of the antifertility action of minimal doses of megestrol acetate in the rabbit.

1. Experiments have been performed to investigate the mechanism by which low doses of megestrol acetate have an antifertility action.2. It was found that the dose of megestrol acetate required to prevent pregnancy in nine of ten New Zealand White rabbits when given on 3 consecutive days, the last of which was the day of insemination, was 50 mug/kg daily.3. This treatment reduced the numbers of sperm recoverable from the uterus at various times after insemination, but egg transfer experiments showed that neither egg viability nor fertilization was affected on day 1 of pregnancy.4. Treatment with megestrol acetate for 3 days caused the fertilized eggs to enter the uterus approximately 48 h prematurely. Treatment with megestrol acetate for longer periods caused a similar but more marked increase in the rate of transport of eggs in the oviduct.5. Megestrol acetate did not modify oviduct opening pressure, but the volume of oviduct fluid secretion was reduced earlier and transport of fluid through the oviduct was accelerated compared with controls.6. Transfer of eggs on various days from the uteri of untreated rabbits to the uteri of treated rabbits indicated that the development of the endometrium which occurs in pregnancy may be advanced by megestrol administration. Histological examination of the endometrial proliferation induced by megestrol acetate confirmed that this was so.7. It is concluded that the antifertility action of megestrol acetate in doses that do not necessarily inhibit ovulation is due to a combination of accelerated egg transport and advanced endometrial development.