Gemzell-Danielsson K, Westlund P, Johannisson E, Swahn M L, Bygdeman M, Seppälä M
Department of Woman and Child Health, Karolinska Hospital, Stockholm, Sweden.
Hum Reprod. 1996 Feb;11(2):256-64. doi: 10.1093/humrep/11.2.256.
The effect of a low dose of mifepristone (RU486) on ovarian and endometrial function was studied in 14 healthy women. The study included one control and two treatment cycles. During the treatment cycles, either 2.5 mg (n = 9) or 5 mg (n = 5) of mifepristone was administered once weekly. The concentration of ovarian steroids and luteinizing hormone (LH) in urine was measured daily, cortisol in blood once weekly and glycodelin (placental protein 14; PP14) at the time of menstruation. Ovarian function was monitored by vaginal ultrasound. An endometrial biopsy was taken in each cycle in the mid-luteal phase, based on self-measurement of the LH peak, or on cycle day 22 if no LH peak could be detected. In the evaluation of the results, the outcome of the enzyme immunoassay of LH was used to date the biopsy. Endometrial progesterone and oestrogen receptors and Dolichus biflorus agglutinin (DBA) lectin binding were measured. Ovulation was not inhibited by treatment with mifepristone, and an LH peak could be determined in all control and treatment cycles. However, in four subjects (one with the higher and three with the lower dose) the follicular phase was prolonged by 6-13 days. The duration of the luteal phase and the concentrations of pregnanediol and oestrone glucuronide were not affected by treatment. A dose of 5 mg, and to a lesser extent 2.5 mg, mifepristone once weekly caused desynchronization of endometrial development. Endometrial progesterone receptor, but not oestrogen receptor, concentration was significantly increased by the higher dose. A significant reduction in DBA-lectin binding and in serum glycodelin concentrations was also found. Thus, low doses of mifepristone do not inhibit ovulation but delay endometrial development and impair secretory activity. Whether these effects are sufficient to prevent implantation remains to be established.
在14名健康女性中研究了低剂量米非司酮（RU486）对卵巢和子宫内膜功能的影响。该研究包括一个对照周期和两个治疗周期。在治疗周期中，每周一次给予2.5毫克（n = 9）或5毫克（n = 5）米非司酮。每天测量尿中卵巢甾体激素和黄体生成素（LH）的浓度，每周一次测量血液中的皮质醇，在月经时测量糖蛋白（胎盘蛋白14；PP14）。通过阴道超声监测卵巢功能。根据LH峰的自我测定，或在未检测到LH峰时在周期第22天，在每个周期的黄体中期进行子宫内膜活检。在结果评估中，使用LH的酶免疫测定结果来确定活检日期。测量子宫内膜孕酮和雌激素受体以及双花扁豆凝集素（DBA）凝集素结合情况。米非司酮治疗未抑制排卵，在所有对照和治疗周期中均可确定LH峰。然而，在4名受试者中（1名高剂量组和3名低剂量组），卵泡期延长了6 - 13天。黄体期的持续时间以及孕二醇和雌酮葡萄糖醛酸苷的浓度不受治疗影响。每周一次给予5毫克米非司酮，在较小程度上给予2.5毫克米非司酮，会导致子宫内膜发育不同步。高剂量组子宫内膜孕酮受体浓度显著增加，但雌激素受体浓度未增加。还发现DBA凝集素结合和血清糖蛋白浓度显著降低。因此，低剂量米非司酮不抑制排卵，但会延迟子宫内膜发育并损害分泌活性。这些作用是否足以防止着床仍有待确定。
