米非司酮黄体期用药对垂体－肾上腺轴的影响

征集健康育龄妇女９例于连续若干周期的黄体晚期单次口服米非司酮，剂量分别依次为２５ｍｇ、１００ｍｇ、４００ｍｇ和６００ｍｇ，并于服药前以及服药后４、８、１２、２４、４８、７２、９６和１２０ｈ采血，以测定血清ＡＣＴＨ和皮质醇。另征集健康育龄妇女１５例，随机分成三组（组Ⅰ～Ⅲ），分别在黄体早、中、晚期给于米非司酮２５ｍｇｑ１２ｈ×６，在ｄ１～ｄ７期间每天采血以测定血清ＡＣＴＨ、皮质醇和米非司酮水平。结果显示米非司酮２５ｍｇ和１００ｍｇ单次口服对ＡＣＴＨ、皮质醇水平及其昼夜分泌节律并无明显影响，可是一次口服高剂量（４００ｍｇ和６００ｍｇ）后，ＡＣＴＨ和皮质醇上午分泌水平增加，昼夜变化幅度明显减少。米非司酮多次用药（２５ｍｑｑ１２ｈ×６）期间，每天上午ＡＣＴＨ和皮质醇几乎无明显变化，黄体期早、中、晚期服药的对象，其血药浓度、ＡＣＴＨ与皮质醇水平均无明显差异。本研究提示对于非妊娠妇女，米非司酮以剂量－依赖的方式显示其抗糖皮质激素活性，只有一次口服大剂量米非司酮才会明显影响其ＡＣＴＨ与皮质醇的昼夜分泌节律。黄体期不同的生殖激素状态对口服米非司酮后的药物吸收及其抗糖皮质激素活性无明显影响。     

Persistent effects of mifepristone (RU-486) on cortisol levels in bipolar disorder and schizophrenia

Recent pre-clinical and clinical studies have examined the potential use of anti-glucocorticoid drug augmentation - including glucocorticoid receptor (GR) antagonists - as a method of improving treatment response in severe psychiatric illness. However, the direct and persistent effects such drugs exert on the hypothalamic-pituitary-adrenal (HPA) axis are unclear. We examined afternoon cortisol levels in 39 patients (19 with bipolar disorder, 20 with schizophrenia) at baseline, following treatment with mifepristone (600mg/day for 7 days) or placebo and at +21 days. Following treatment with mifepristone (day +7) there was a significant increase in cortisol levels from baseline (mean change=60,434nmol/Lxmin, 95%CI=44,755-76,112; t=7.803, df=38, p<0.0001) which significantly decreased from this point by day +21 (mean change=-64,487nmol/Lxmin, 95%CI=-49,974 to -79,001; t=8.995, df=38, p<0.0001). Cortisol levels at day +21 were significantly lower than they were at baseline (mean change=-4054nmol/Lxmin, 95%CI=-456 to -7652; t=2.281, df=38, p=0.028). No significant changes occurred following placebo. These results provide preliminary evidence that subtle but significant reductions in HPA axis activity (measured by peripheral cortisol levels) are evident 14 days after cessation of treatment with the GR-antagonist mifepristone. This may in part underlie the putative therapeutic effects of such drugs.     

米非司酮黄体期用药对垂体－肾上腺轴的影响

征集健康育龄妇女９例于连续若干周期的黄体晚期单次口服米非司酮，剂量分别依次为２５ｍｇ、１００ｍｇ、４００ｍｇ和６００ｍｇ，并于服药前以及服药后４、８、１２、２４、４８、７２、９６和１２０ｈ采血，以测定血清ＡＣＴＨ和皮质醇。另征集健康育龄妇女１５例，随机分成三组（组Ⅰ～Ⅲ），分别在黄体早、中、晚期给于米非司酮２５ｍｇｑ１２ｈ×６，在ｄ１～ｄ７期间每天采血以测定血清ＡＣＴＨ、皮质醇和米非司酮水平。结果显示米非司酮２５ｍｇ和１００ｍｇ单次口服对ＡＣＴＨ、皮质醇水平及其昼夜分泌节律并无明显影响，可是一次口服高剂量（４００ｍｇ和６００ｍｇ）后，ＡＣＴＨ和皮质醇上午分泌水平增加，昼夜变化幅度明显减少。米非司酮多次用药（２５ｍｑｑ１２ｈ×６）期间，每天上午ＡＣＴＨ和皮质醇几乎无明显变化，黄体期早、中、晚期服药的对象，其血药浓度、ＡＣＴＨ与皮质醇水平均无明显差异。本研究提示对于非妊娠妇女，米非司酮以剂量－依赖的方式显示其抗糖皮质激素活性，只有一次口服大剂量米非司酮才会明显影响其ＡＣＴＨ与皮质醇的昼夜分泌节律。黄体期不同的生殖激素状态对口服米非司酮后的药物吸收及其抗糖皮质激素活性无明显影响。     

Effects of adjunctive mifepristone (RU-486) administration on neurocognitive function and symptoms in schizophrenia.

BACKGROUND: It has been suggested that hypercortisolemia may cause or exacerbate both neurocognitive impairment and symptoms in schizophrenia. We hypothesized that antiglucocorticoid treatments, particularly glucocorticoid receptor (GR) antagonists, would improve neurocognitive functioning and clinical symptoms in this disorder. METHOD: Twenty patients with schizophrenia were treated with 600 mg/day of the GR-antagonist mifepristone (RU-486) or placebo for 1 week in a double-blind, crossover design. Neurocognitive function was evaluated at baseline and 2 weeks after each treatment. Neuroendocrine profiling was performed at these times and also immediately after each treatment. Symptoms were evaluated weekly. RESULTS: Mifepristone administration resulted in a temporary two- to threefold increase in plasma cortisol levels (p < .0001). No significant effects were observed on any measure of neurocognitive function, including the primary outcome measures of spatial working memory and declarative memory. Minor changes in symptoms occurred in both arms of the study and were indicative of a general improvement over time, irrespective of treatment. CONCLUSIONS: In contrast to our earlier report of positive effects in bipolar disorder, these data suggest that the GR-antagonist mifepristone has no effect on neurocognitive function or symptoms in this group of patients with schizophrenia. Future studies in schizophrenia should examine patients with demonstrable hypothalmic-pituitary-adrenal axis dysfunction.     

Mifepristone and misoprostol sequential regimen side effects, complications and safety

Exhibiting a strong affinity to the progesterone and the glucocorticoid receptors, mifepristone exert competitive antagonism to these hormones both in in vitro and in animal experiments. Due to its antiprogesterone activity, it was proposed that mifepristone be used for the termination of early human pregnancy. Mifepristone, at a dose of 600 mg initially used alone, was then used with a subsequent low dose of prostaglandin that led to a success rate of 95% as a medical method for early termination of pregnancy (TOP), and the occurrence of continuing pregnancy was reduced to 相似文献