A single mid-follicular dose of CDB-2914, a new antiprogestin, inhibits folliculogenesis and endometrial differentiation in normally cycling women
A single mid-follicular dose of CDB-2914, a new antiprogestin, inhibits folliculogenesis and endometrial differentiation in normally cycling women
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DOI：
10.1093/humrep/15.5.1092
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发表时间：
2000-05-01
影响因子：
6.1
通讯作者：
Nieman, LK
中科院分区：
文献类型：
--
作者：
Stratton, P;Hartog, B;Nieman, LK
先前对女性的研究表明，抗孕激素米非司酮会延迟或抑制卵泡发生。本研究的目的是探讨新的类似物 CDB-2914 是否对卵泡发生、排卵或随后的黄体期子宫内膜成熟具有类似的影响。 44 名正常循环的健康女性在治疗前、治疗和治疗后周期记录了尿液 LH 和阴道出血。卵泡直径14-16 mm时，单次口服（10、50、100 mg）CDB-2914或安慰剂，每日超声、雌二醇和孕酮检测，直至卵泡塌陷； 5-7天后进行子宫内膜活检。单剂量的 CDB-2914 耐受性良好。卵泡中部 CDB-2914 抑制卵泡生长，导致卵泡发生剂量依赖性延迟并抑制血浆雌二醇。在较高剂量下，经常会募集新的先导卵泡。尽管在 100 毫克剂量下观察到黄素化的未破裂卵泡，但所有女性均出现卵泡塌陷。所有剂量的 CDB-2914 后子宫内膜成熟均出现显着延迟。治疗周期延长 1-2 周，100 mg 时延长 30%，50 mg 时延长 27%，10 mg 时延长 9%。 CDB-2914 改变了卵巢和子宫内膜的生理机能，但对月经周期没有重大影响，并且可能具有治疗作用。
Previous studies in women have shown that the antiprogestin mifepristone delays or inhibits folliculogenesis. The purpose of this study was to explore whether a new analogue, CDB-2914, has similar effects on folliculogenesis, ovulation, or on subsequent luteal phase endometrial maturation. Forty-four normally cycling, healthy women recorded urine LH and vaginal bleeding during pre-treatment, treatment, and post-treatment cycles. At a lead follicle diameter of 14-16 mm, a single oral dose (10, 50, 100 mg) of CDB-2914 or placebo was given, and daily ultrasound, oestradiol and progesterone were obtained until follicular collapse; an endometrial biopsy was obtained 5-7 days later. Single doses of CDB-2914 were well tolerated. Mid-follicular CDB-2914 suppressed lead follicle growth, causing a dose-dependent delay in folliculogenesis and suppression of plasma oestradiol. At higher doses, a new lead follicle was often recruited. Although luteinized unruptured follicles were observed at the 100 mg dose, all women had follicular collapse. There was a significant delay in endometrial maturation after CDB-2914 at all doses. The treatment cycle was lengthened by 1-2 weeks in 30% at 100, 27% at 50 and 9% at 10 mg. CDB-2914 altered ovarian and endometrial physiology without major effects on menstrual cyclicity and may have therapeutic utility.