Swahn M L, Bygdeman M, Seppälä M, Johannisson E, Cekan S
Department of Obstetrics and Gynaecology, Karolinska Hospital, Stockholm, Sweden.
Hum Reprod. 1993 Feb;8(2):193-200. doi: 10.1093/oxfordjournals.humrep.a138021.
The effects of RU 486 combined with tamoxifen and tamoxifen alone on hormonal parameters and endometrial development at the time of implantation were studied. Measurements of cytosolic oestrogen and progesterone receptors in endometrium and placental protein 14 (PP14) in plasma were also included. Three dosage schedules were used: single oral dose of 40 mg tamoxifen alone and in combination with 200 mg RU 486, and 40 mg tamoxifen for three consecutive days starting on the first day after the luteinizing hormone (LH) surge. The combined treatment prolonged the luteal phase (P < 0.05) and increased the plasma levels of progesterone. A single dose of tamoxifen did not affect the bleeding pattern and plasma hormone levels, but raised plasma oestradiol and LH with the 3-day treatment. The endometrium was retarded after the combined and the 3-day treatment with tamoxifen. Concentrations of cytosolic progesterone receptors were higher after the combined therapy, but were unaffected after tamoxifen only. PP14 levels were higher (P < 0.05) after repeated tamoxifen doses than in controls, but were lower with combined treatment. Progesterone and oestrogen are evidently necessary for endometrial maturation during the secretory phase of the menstrual cycle. PP14 levels in plasma cannot be used for clinical assessments of endometrial function because high levels coincide with disturbed endometrial development.
研究了米非司酮联合他莫昔芬及单独使用他莫昔芬对植入时激素参数和子宫内膜发育的影响。还包括对子宫内膜胞质雌激素和孕激素受体以及血浆中胎盘蛋白14(PP14)的测量。使用了三种给药方案:单独口服40mg他莫昔芬以及与200mg米非司酮联合使用,以及在促黄体生成素(LH)高峰后的第一天开始连续三天服用40mg他莫昔芬。联合治疗延长了黄体期(P<0.05)并提高了血浆孕酮水平。单次剂量的他莫昔芬不影响出血模式和血浆激素水平,但在三天治疗后会升高血浆雌二醇和LH。联合治疗以及他莫昔芬三天治疗后子宫内膜发育延迟。联合治疗后胞质孕激素受体浓度较高,但仅使用他莫昔芬时不受影响。多次服用他莫昔芬后PP14水平高于对照组(P<0.05),但联合治疗时较低。孕酮和雌激素显然是月经周期分泌期子宫内膜成熟所必需的。血浆中的PP14水平不能用于子宫内膜功能的临床评估,因为高水平与子宫内膜发育紊乱同时出现。