Brown Audrey, Cheng Linan, Lin Suiqing, Baird David T
Contraceptive Development Network, Centre for Reproductive Biology, University of Edinburgh, Edinburgh, EH3 9ET, United Kingdom.
J Clin Endocrinol Metab. 2002 Jan;87(1):63-70. doi: 10.1210/jcem.87.1.8140.
Daily administration of progesterone (P) antagonists to women inhibits ovulation and disrupts endometrial function. In this double-blind randomized trial, we have explored the contraceptive potential of two doses of the P antagonist mifepristone in healthy volunteers in Edinburgh and Shanghai. Ninety-eight women (58 in Edinburgh and 40 in Shanghai) were randomized to receive either 2 or 5 mg mifepristone daily for 120 d. Ovarian activity was monitored by the weekly measurement of steroid metabolites in urine and of E2 and P in plasma every month. Endometrial function was assessed by menstrual records, and ultrasound measurement of endometrial thickness was assessed every month. Endometrial biopsy was collected on d 12 of the control cycle and after 60 and 120 d of treatment. Ninety women (50 in Edinburgh and 40 in Shanghai) completed the study. Follicular activity continued during treatment with both doses in Edinburgh women, although ovulation was suppressed in the majority of cycles (90 and 95% of cycles in 2- and 5-mg groups, respectively). The women in Shanghai showed evidence of ovulation in only 3 of 160 months of treatment (2 in 2-mg group and 1 in 5-mg group). The majority of women in both centers were amenorrheic (65% in 2-mg group and 88% in 5-mg group in Edinburgh, and 90% in both dose groups in Shanghai). The endometrial thickness increased significantly in women in Edinburgh and decreased in Shanghai; histology showed either atrophic or cystic changes without evidence of hyperplasia. There was no pregnancy reported in the 200 months of exposure in 50 sexually active women who had used no other method of contraception during the study. We conclude that mifepristone in low daily doses inhibits ovulation and induces amenorrhea in the majority of women and has the potential to be developed as a novel estrogen- free oral contraceptive pill.
每日给女性服用孕酮（P）拮抗剂会抑制排卵并扰乱子宫内膜功能。在这项双盲随机试验中，我们在爱丁堡和上海的健康志愿者中探索了两种剂量的P拮抗剂米非司酮的避孕潜力。98名女性（爱丁堡58名，上海40名）被随机分为两组，每天分别服用2毫克或5毫克米非司酮，持续120天。通过每周测量尿液中的类固醇代谢物以及每月测量血浆中的雌二醇（E2）和孕酮（P）来监测卵巢活动。通过月经记录评估子宫内膜功能，并每月通过超声测量子宫内膜厚度。在对照周期的第12天以及治疗60天和120天后采集子宫内膜活检样本。90名女性（爱丁堡50名，上海40名）完成了研究。在爱丁堡的女性中，两种剂量治疗期间卵泡活动均持续存在，尽管大多数周期（2毫克组和5毫克组分别为90%和95%的周期）排卵受到抑制。上海的女性在160个月的治疗中仅有3个月有排卵迹象（2毫克组2例，5毫克组1例）。两个中心的大多数女性均闭经（爱丁堡2毫克组为65%，5毫克组为88%；上海两个剂量组均为90%）。爱丁堡女性的子宫内膜厚度显著增加，而上海女性的子宫内膜厚度则下降；组织学检查显示为萎缩或囊性改变，无增生迹象。在50名性活跃女性200个月的暴露期内，她们在研究期间未使用其他避孕方法，均未报告怀孕。我们得出结论，低剂量每日服用米非司酮可抑制大多数女性排卵并导致闭经，有潜力开发成为一种新型无雌激素口服避孕药。
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