ENDOMETRIAL EFFECT OF ANTIPROGESTIN RELEAS INTRAUTER DEVICE IN NON HUMAN PRIMATE

这项研究的目标是开发一种抗孕激素释放 宫内节育器(IUD)，这可能是一种避孕措施， 或抑制子宫内膜出血。与Leiras Oy合作， 芬兰，先灵公司的子公司，我们测试了两种类型的宫内节育器 释放新的抗孕激素ZK 230 211(ZK211)。其中一人释放了一种高潮 剂量(26-30.2克/天)和低剂量(3.3-4.5克/天) 211/天)。短尾猕猴最初被认为是最 适合这个项目的物种，因为它们的宫颈是 与其他普通实验室S形宫颈的比较 猕猴。然而，我们在插入宫颈时遇到了很大的困难。 并发现，虽然外部操作系统和 颈管笔直，容易插管，内口是 非常小，本身就是S形状的。提供信息 与项目目标相关，高剂量和低剂量宫内节育器被放置在 短尾猴和猪尾猕猴子宫切除。我们的第一项研究 旨在测试抗孕激素宫内节育器是否可以抑制 黄体酮对子宫内膜的影响。低剂量和大剂量宫内节育器 在放置宫内节育器后三天内诱导月经。这 表明当地产生的抗孕激素的数量 大剂量和小剂量宫内节育器足以防止全身性 孕酮维持孕期子宫内膜的作用 州政府。这些猴子被用来诱导人工月经周期。 在一个周期结束时收集组织。子宫内膜 暴露在空白宫内节育器中与典型的宫内节育器没有显著差异 孕期子宫内膜，但子宫内膜量 组织比正常状态结束时预期的要少一些 周而复始。抗孕激素宫内节育器导致严重的宫内压实 间质与P对双腺体的抑制作用 球囊和螺旋动脉发育。有证据表明 血管周围脂肪变性类似于长时间后观察到的 术语全身性抗孕激素。这些结果表明，急性 宫内节育器局部应用抗孕激素可抑制 子宫内膜发育，可能是全身性的替代 控制子宫内膜出血或以子宫为基础的治疗 避孕药。资助拉勒基金会出版物无

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