Narvekar Nitish, Critchley Hilary O D, Cheng Linan, Baird David T
Contraceptive Development Network, Centre for Reproductive Biology, Edinburgh, UK.
Hum Reprod. 2006 Sep;21(9):2312-8. doi: 10.1093/humrep/del182. Epub 2006 Jun 28.
We have previously shown that the progesterone antagonist mifepristone is a contraceptive when given in a dose of 2 or 5 mg per day. The majority of women experience amenorrhoea rather than the irregular break through bleeding usually occurring with other estrogen-free contraceptive pills, such as progestogen-only pill (POP). We investigated the effects of low-dose mifepristone on endometrial parameters which may be associated with changes in endometrial function, such as microvasculature, vascular endothelial growth factor (VEGF) and glucocorticoid receptor (GR) content.
Endometrial biopsies were collected from 16 women before (late proliferative phase) and 60 and 120 days after taking 2 or 5 mg mifepristone daily for 120 days. Seven of the eight women who received 2 mg mifepristone and all eight women who received 5 mg were amenorrhoeic during the study. Mean estradiol (E(2)) concentrations remained in the mid-proliferative range, and the majority (9/16) of women showed proliferative endometrial histology at 60 and 120 days following treatment. There was a significant increase in the density of the endometrial stroma (P < 0.05) and microvessels (P < 0.01) following 120 days of treatment. Immunocytochemistry showed that GR, hitherto localized specifically in endometrial stroma, was up-regulated in the nuclei of glands (P < 0.05) and surface (luminal) epithelium (P < 0.01) by 60 days and maintained at 120 days. There was a significant reduction in stromal VEGF protein expression by day 120 of treatment (P < or = 0.01).
The high incidence of amenorrhoea in women taking mifepristone may be related to changes in the regulation of vascular function.
我们之前已经表明，孕酮拮抗剂米非司酮以每日2毫克或5毫克的剂量给药时具有避孕作用。与其他不含雌激素的避孕药（如仅含孕激素的避孕药）通常出现的不规则突破性出血不同，大多数女性出现闭经。我们研究了低剂量米非司酮对子宫内膜参数的影响，这些参数可能与子宫内膜功能变化相关，如微血管、血管内皮生长因子（VEGF）和糖皮质激素受体（GR）含量。
从16名女性在服用米非司酮每日2毫克或5毫克共120天之前（增殖晚期）以及服药60天和120天后采集子宫内膜活检样本。在研究期间，接受2毫克米非司酮的8名女性中有7名以及接受5毫克米非司酮的所有8名女性均闭经。平均雌二醇（E₂）浓度保持在增殖中期范围，并且大多数（9/16）女性在治疗后60天和120天显示增殖期子宫内膜组织学。治疗120天后，子宫内膜基质密度（P < 0.05）和微血管密度（P < 0.01）显著增加。免疫细胞化学显示，迄今特异性定位于子宫内膜基质的GR，在60天时在腺体（P < 0.05）和表面（腔）上皮（P < 0.01）细胞核中上调，并在120天时维持上调状态。治疗至120天时，基质VEGF蛋白表达显著降低（P ≤ 0.01）。
服用米非司酮的女性中闭经的高发生率可能与血管功能调节的变化有关。
