REVERSIBLE SUPPRESSION OF MENSTRUATION W/ ANTIPROGESTINS

使用抗孕激素可逆性抑制月经

• 批准号: 6592354
• 负责人: ROBERT M BRENNER
• 金额: $ 11.11万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-05-01 至 2003-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6592354
• 关键词: Mammalia; hormones; model design /development; reproductive system

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.

我们这项研究的目标是开发一种安全、可逆的方法 用一类化合物抑制月经 抗孕激素。 之前我们表明短期系统性 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研究 使用 ZK316 治疗的循环恒河猴。 在这项研究中，所有 动物表现出正常的治疗前月经周期（平均值_SE； 28.3 _ 1.4 天）。 注射 ZK316 0.05 和 0.1 mg/kg，共 100 粒 月经受阻的天数明显延长 所有猴子的月经间隔。 经间期 对照组、0.05组和0.1组的间隔分别为28.1_0.83、131.1_ 分别为 10.1 和 134 _ 8.7 天（P < 0.001）。 过去 30 年间 治疗天数后，对照组猴子的表达正常 雌二醇（E2）和黄体酮（P）的月经周期模式。 在 此外，0.05 mg/kg ZK316 组中的所有猴子 (n = 4) 卵泡期 E2 水平正常（包括 E2 激增）并且 P 的正常黄体期水平。在该组中，ZK316 抑制 尽管黄体期 P 期结束时正常下降，但月经仍持续 循环。 然而，0.1 mg/kg 组的所有猴子都失败了 产生正常的 E2 激增（E2 水平升至 200 pg/ml 以上）或 最后 30 天内 P 的正常黄体期水平 (>1 ng/ml) 治疗。 尽管该组的排卵受阻，但所有 猴子的 E2 水平显示出正常的非激增水平（~30-100 pg/ml）。 所有接受 ZK316 治疗的猴子在 40 天内恢复正常周期 所有组的治疗后周期长度均正常（29.8 _ 3.0 天）。 未发现治疗不良反应 研究期间的猴子。 总之，我们现在已经证明了 长期抗孕激素治疗会可逆地抑制月经 在恒河猴中。