Baird D T, Thong K J, Hall C, Cameron S T
Department of Obstetrics and Gynaecology, University of Edinburgh, UK.
Hum Reprod. 1995 Sep;10(9):2270-6. doi: 10.1093/oxfordjournals.humrep.a136283.
It has been demonstrated previously that administration of the antiprogestin mifepristone (RU 486; 1-5 mg daily) inhibits or delays both the pre-ovulatory luteinizing hormone (LH) surge and ovulation. To investigate this mechanism, dynamic tests of pituitary ovarian function were performed in six healthy women before and during the administration of mifepristone (2 mg daily for 30 days). On day 9 of the control and treatment cycles, samples of blood were collected every 15 min over 12 h for measurement of LH concentration. After 10 h, the responsiveness of the pituitary was tested by the i.v. injection of 10 micrograms of gonadotrophin-releasing hormone (GnRH). On day 10 of the control and treatment cycles, two patches releasing 200 micrograms/day of oestradiol were applied to skin on the abdomen for 3 days. Blood was collected at 24, 48, 59, 72, 81 and 96 h after application of the oestrogen patches for the measurement of gonadotrophin and ovarian hormone concentrations. Follicular development continued in all women during their treatment with mifepristone, and ovulation was suppressed (four women) or delayed (two women). There was no significant difference in the basal concentration of LH between the control and treatment cycles (mean +/- SE; 5.5 +/- 0.4 versus 7.7 +/- 0.4 IU/l respectively), or in the frequency (interpulse interval, 101 +/- 12 versus 105 +/- 13 min respectively) and the amplitude (2.1 +/- 0.4 versus 2.6 +/- 0.4 IU/l respectively) of LH pulses. The response to GnRH was similar. On day 10, the basal concentrations of LH, follicle-stimulating hormone (FSH), prolactin, oestradiol and progesterone and the diameter of the dominant follicle (15.7 +/- 1.8 versus 13.3 +/- 1.9 mm) were similar during control and treatment cycles. In control cycles, there were significant increases in the concentrations of LH and FSH within 72 h of application of the oestrogen patches. During treatment cycles, concentrations of FSH and LH remained low, and were significantly lower than the values observed during control cycles (P < 0.006). We conclude that the antiprogestin mifepristone disrupts ovulation by inhibiting the positive feedback effect of oestrogens and, hence, prevents or delays the generation of a pre-ovulatory LH surge.
先前已证实，给予抗孕激素米非司酮（RU 486；每日1 - 5毫克）可抑制或延迟排卵前促黄体生成素（LH）峰及排卵。为研究此机制，对6名健康女性在服用米非司酮（每日2毫克，共30天）之前及期间进行了垂体卵巢功能的动态测试。在对照周期和治疗周期的第9天，每隔15分钟采集一次血样，持续12小时，以测定LH浓度。10小时后，通过静脉注射10微克促性腺激素释放激素（GnRH）来测试垂体的反应性。在对照周期和治疗周期的第10天，将两片每日释放200微克雌二醇的贴片贴于腹部皮肤，持续3天。在应用雌激素贴片后24、48、59、72、81和96小时采集血样，以测定促性腺激素和卵巢激素浓度。在所有女性服用米非司酮治疗期间，卵泡发育持续进行，排卵受到抑制（4名女性）或延迟（2名女性）。对照周期和治疗周期之间LH的基础浓度无显著差异（均值±标准误；分别为5.5±0.4与7.7±0.4 IU/L），LH脉冲的频率（脉冲间期，分别为101±12与105±13分钟）和幅度（分别为2.1±0.4与2.6±0.4 IU/L）也无显著差异。对GnRH的反应相似。在第10天，对照周期和治疗周期之间LH、促卵泡生成素（FSH）、催乳素、雌二醇和孕酮的基础浓度以及优势卵泡直径（15.7±1.8与13.3±1.9毫米）相似。在对照周期中，应用雌激素贴片后72小时内LH和FSH浓度显著升高。在治疗周期中，FSH和LH浓度保持较低水平，且显著低于对照周期中观察到的值（P < 0.006）。我们得出结论，抗孕激素米非司酮通过抑制雌激素的正反馈作用来干扰排卵，从而预防或延迟排卵前LH峰的产生。
