REVERSIBLE SUPPRESSION OF MENSTRUATION W/ ANTIPROGESTINS

我们这项研究的目标是开发一种安全、可逆的方法 抑制月经的一类化合物 抗孕激素。此前我们曾表示，短期系统性 先灵抗孕激素ZK 137 316(ZK316)治疗将 抑制月经。我们现在进行了一项长期的研究 ZK316对骑行恒河猴的影响。在这项研究中，所有的 动物表现出正常的治疗前月经周期(Mean_SE； 28.3~1.4天)。注射用ZK316 0.05 mg/kg和0.1 mg/kg 100 天数阻碍了月经，并显著延长了 所有猴子的月经间歇期。月经间期 对照组、0.0 5组和0.1组的时间间隔分别为28.1~0.83、131.1~ 10.1d和134.7d(P&lt；0.001)。在过去30年中 经过几天的治疗，对照组的猴子表现正常 雌激素(E_2)和孕酮(P)的月经周期模式。在……里面 另外，ZK316 0.05 mg/kg组(n=4) 卵泡期E2水平正常(包括E2激增)和 在本组中，ZK316抑制了正常黄体期的P。 月经，尽管黄体P期末正常下降 这个循环。然而，0.1 mg/kg组的所有猴子都失败了 出现正常的雌二醇峰(雌二醇水平高于200 pg/ml)或 黄体期P(&gt；1 ng/ml)在黄体期最后30天的正常水平 治疗。尽管这组人阻止了排卵，但所有的 猴子表现出正常的非高峰水平(~30-100 pg/ml)。 所有ZK316治疗的猴子在40天内恢复正常的周期性 治疗后周期长度在所有组均正常(29.8 _3.0天)。未检测到治疗的不良反应。 研究中的猴子。总而言之，我们现在已经表明 长期的抗孕激素治疗将可逆地抑制月经 在恒河猴身上。

Our goal in this research is to develop a safe, reversible method of menstrual suppression with a class of compounds called antiprogestins. Previously we showed that short-term systemic treatment with the Schering antiprogestin ZK 137 316 (ZK316) will suppress menstruation. We have now conducted a long-term study of cycling rhesus monkeys treated with ZK316. In this study, all of the animals exhibited normal pretreatment menstrual cycles (mean _ SE; 28.3 _ 1.4 days). Injection with ZK316 at 0.05 and 0.1 mg/kg for 100 days blocked menstruation and significantly extended the intermenstrual interval in all of the monkeys. Intermenstrual interval in the control, 0.05 and 0.1 groups were 28.1 _ 0.83, 131.1 _ 10.1 and 134 _ 8.7 days, respectively (P < 0.001). During the last 30 days of treatment, the monkeys in the control group expressed normal menstrual cycle patterns of estradiol (E2) and progesterone (P). In addition, all of the monkeys in the 0.05 mg/kg ZK316 grou p (n = 4) had normal follicular phase levels of E2 (including an E2 surge) and normal luteal phase levels of P. In this group, ZK316 suppressed menstruation despite a normal decline in luteal phase P at the end of the cycle. However, all of the monkeys in the 0.1 mg/kg group failed to develop a normal E2 surge (E2 levels rising above 200 pg/ml) or normal luteal phase levels of P (>1 ng/ml) during the last 30 days of treatment. Despite blockade of ovulation in this group, all of the monkeys showed normal nonsurge levels of E2 levels (~30-100 pg/ml). All ZK316-treated monkeys returned to normal cyclicity within 40 days and posttreatment cycle lengths were normal in all of the groups (29.8 _ 3.0 days). No untoward effects of treatment were detected in the monkeys during the study. In summary, we have now shown that long-term antiprogestin treatment will reversibly inhibit menstruation in rhesus monkeys.