ENDOMETRIAL EFFECT OF ANTIPROGESTIN RELEAS INTRAUTER DEVICE IN NON HUMAN PRIMATE

本研究的目的是开发一种抗孕激素释放剂， 子宫内避孕器（IUD），可用作避孕药， 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， 发布新的抗胰蛋白酶ZK 230 211（ZK 211）。 一个释放出高 剂量（26-30.2？低剂量组（3.3-4.5 μ g/d）;克ZK 211人/天）。 短尾猕猴最初被认为是世界上 适合这个项目的物种，因为它们的子宫颈 与其他普通实验室的S形宫颈相比， 猕猴 然而，我们在子宫颈插管时遇到了很大的困难 发现虽然外部操作系统和 宫颈管直，易于插管，内口 非常小，本身就是S形。 提供资料 与项目目标相关，插入了高剂量和低剂量宫内节育器 通过子宫切除术切除截尾和猪尾艾德猕猴。 我们的第一项研究 目的是检测抗孕酮宫内节育器是否能抑制 孕激素对子宫内膜的影响 低剂量和高剂量IUD 在放置宫内节育器后三天内诱导月经。 这 这表明，由两种药物在当地产生的抗孕酮的量， 高、低剂量宫内节育器足以预防全身性宫内节育器丢失， 孕激素维持孕前期子宫内膜 状态 这些猴子被用来诱导人工月经周期 并在一个循环结束时收集组织。 子宫内膜 暴露于空白宫内节育器显示与典型的 妊娠前子宫内膜，除了子宫内膜的量 组织比正常结束时预期的要少一些。 周期 抗孕激素宫内节育器引起了严重的压实， 间质和抑制的影响，P对两个腺 囊状形成和螺旋动脉发育。 有证据表明 血管周围透明变性类似于长时间 术语全身性抗前列腺素。 这些结果表明，急性 通过IUD局部给予抗孕酮可抑制 子宫内膜发育，可能是系统性的替代方案， 控制子宫内膜出血或作为子宫基础的治疗 避孕药 资助Lalor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