Antifertiflty Effects in the Rabbit by Continuous Low Release of Progestin from an Intrauterine Device

Abstract

The contraceptive efficacy of continuous local application of chlormadinone acetate (CA) and progesterone (P) has been investigated in the rabbit, using as a drug-delivery system intrauterine devices (IUDs) constructed of silicone elastomer. Placebo IUDs and those giving lowest release rate of P in vitro (6 μg/day) were expelled from the uterus even when sutured through the wall, although higher release rates of P and all levels of CA caused retention in all cases. Horns which had contained placebo IUDs showed a low implantation rate, an effect which tended to be reversed at low release rates of either CA (19 μg/day in vitro) or P (6 μg/day in vitro). At higher release rates of either CA or P a dose-related antifertility effect was exerted. Comparison of endometrial proliferation in adult rabbits resulting from intrauterine instillation of CA or P in oil with that resulting from IUD delivery suggested that the release rate from IUDs at effective contraceptive levels was greatly in excess of that required for full progestational proliferation. As systemic uptake from the IUDs, reflected by full progestational proliferation of contralateral horns, was consistent with normal pregnancy, it was suggested that the contraceptive effect was mediated through local effects of the progestins.