ENDOMETRIAL EFFECT OF ANTIPROGESTIN RELEAS INTRAUTER DEVICE IN NON HUMAN PRIMATE

Oregon Health And Science University, Portland OR

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Abstract

The goal of this study is to develop an antiprogestin-releasing intrauterine device (IUD), which might be applied as a contraceptive, or to inhibit endometrial bleeding. In collaboration with Leiras OY, Finland, a subsidiary of Schering AG, we tested two types of IUDs that release the new antiprogestin ZK 230 211 (ZK211). One released a high dose (26-30.2 ?g ZK 211/day) and the other a low dose (3.3-4.5 ?g ZK 211/day). Stumptail macaques were originally considered as the most suitable species for this project as they have a cervix that is straight compared to the S-shaped cervix of other common laboratory macaques. However, we had great difficulty in cannulating the cervix of the stumptails and discovered that while the external os and the cervical canal are straight and easy to cannulate, the internal os is extremely small and is itself S-shaped. To provide information relevant to the project goals, high and low dose IUDs were inserted in stumptailed and pig tail ed macaques by hysterectomy. Our first study was designed to test whether antiprogestin IUDs could inhibit the endometrial effects of progesterone. Both the low and high dose IUDs induced menstruation within three days of inserting the IUDs. This indicated that the amount of antiprogestin produced locally by both the high and low dose IUDs was sufficient to prevent systemic progesterone from maintaining the endometrium in a progestational state. The monkeys were treated to induce artificial menstrual cycles and tissues were collected at the end of one cycle. The endometrium exposed to the blank IUD showed no major differences from a typical progestational endometrium, except that the amount of endometrial tissue was somewhat less than would be expected at the end of a normal cycle. The antiprogestin IUDs caused a severe compaction of the stroma and an inhibition of the effects of P on both glandular sacculation and spiral artery development. There was evidence of perivascular hy aline degeneration similar to that observed after long term systemic antiprogestin. These results suggest that acute administration of local antiprogestin by IUD can act to inhibit endometrial development and may represent an alternative to systemic treatment to control endometrial bleeding or as a uterine based contraceptive. FUNDING Lalor Foundation PUBLICATIONS None