Ottosson U B
Acta Obstet Gynecol Scand Suppl. 1984;127:1-37. doi: 10.3109/00016348409157016.
The pharmacokinetics of progesterone after oral administration were investigated. After a single dose of 100 mg, serum concentrations of progesterone around 50-60 nM and of 20 alpha-hydroxy-4-pregnene-3-one around 5-6 nM were recorded within 1-4 hours and elevated levels persisted for 8-12 hours. There were only minor changes in 17 alpha-hydroxyprogesterone concentrations and serum levels of androstenedione and cortisol were unaffected. A significant conversion of circulating progesterone into deoxy-corticosterone was demonstrated. During clinical treatment with oral progesterone the individual serum concentrations of this potent mineralocorticoid were closely correlated to the progesterone concentrations. This observation could be important as regards the etiology of certain clinical disorders characterized by fluid retention. According to competitive binding analyses there was no evidence that progesterone or medroxyprogesterone acetate could cause significant displacement of cortisol from corticosteroid-binding globulin during clinical treatment. The effects of natural and synthetic hormones upon subfractions of high density lipoprotein (HDL) cholesterol and liver proteins were followed in postmenopausal women during replacement therapy with various estrogen-progestogen combinations. The total serum cholesterol level was significantly reduced during treatment with all estrogen regimens. The concentrations of HDL cholesterol, HDL2 cholesterol, apolipoprotein A I and A II were increased in a dose-dependent pattern during unopposed estrogen therapy. The potency of 10 micrograms of ethinyl estradiol was estimated to be equivalent to 3-4 mg of estradiol valerate. Estrogen effects were significantly reversed by levonorgestrel 250 micrograms and also by medroxyprogesterone acetate 10 mg. During treatment with natural progesterone, no changes were recorded in HDL cholesterol or its subfractions. As compared with the lipoproteins, pregnancy zone protein and sex hormone binding globulin (SHBG) were found to be more sensitive to the alkylated than to the non-alkylated estrogen. Both levonorgestrel and medroxyprogesterone acetate clearly reduced SHBG levels after 3 months, whereas micronized progesterone had no such effect. While tamoxifen counteracted the therapeutic and metabolic effects of estrogen the sequential addition of estriol had no apparent influence. Unopposed estrogen treatment enhanced liver lecithin synthesis along pathway I, i.e. reduced the amount of stearic acid and increased the amount of palmitic acid. The effects were dose-dependent and no qualitative differences between ethinyl estradiol and estradiol valerate were recorded.
研究了口服黄体酮后的药代动力学。单次服用100毫克后，1 - 4小时内记录到黄体酮血清浓度约为50 - 60纳摩尔，20α-羟基-4-孕烯-3-酮血清浓度约为5 - 6纳摩尔，且升高水平持续8 - 12小时。17α-羟基孕酮浓度仅有轻微变化，雄烯二酮和皮质醇的血清水平未受影响。已证实循环中的黄体酮可显著转化为脱氧皮质酮。在口服黄体酮的临床治疗期间，这种强效盐皮质激素的个体血清浓度与黄体酮浓度密切相关。就某些以液体潴留为特征的临床疾病的病因而言，这一观察结果可能具有重要意义。根据竞争性结合分析，没有证据表明在临床治疗期间黄体酮或醋酸甲羟孕酮会导致皮质醇从皮质类固醇结合球蛋白上显著置换下来。在绝经后妇女接受各种雌激素 - 孕激素组合替代治疗期间，观察了天然和合成激素对高密度脂蛋白（HDL）胆固醇亚组分和肝脏蛋白的影响。在所有雌激素治疗方案中，总血清胆固醇水平均显著降低。在单纯雌激素治疗期间，HDL胆固醇、HDL2胆固醇、载脂蛋白A I和A II的浓度呈剂量依赖性增加。估计10微克乙炔雌二醇的效力相当于3 - 4毫克戊酸雌二醇。左炔诺孕酮250微克和醋酸甲羟孕酮10毫克均可显著逆转雌激素的作用。在天然黄体酮治疗期间，HDL胆固醇及其亚组分未记录到变化。与脂蛋白相比，妊娠区蛋白和性激素结合球蛋白（SHBG）对烷基化雌激素比对非烷基化雌激素更敏感。左炔诺孕酮和醋酸甲羟孕酮在3个月后均明显降低SHBG水平，而微粉化黄体酮则无此作用。虽然他莫昔芬可抵消雌激素的治疗和代谢作用，但序贯添加雌三醇没有明显影响。单纯雌激素治疗可沿途径I增强肝脏卵磷脂合成，即减少硬脂酸含量并增加棕榈酸含量。这些作用具有剂量依赖性，且未记录到乙炔雌二醇和戊酸雌二醇之间的质量差异。
