Harris A L, Dowsett M, Smith I E, Jeffcoate S
Eur J Cancer Clin Oncol. 1984 Apr;20(4):463-9. doi: 10.1016/0277-5379(84)90230-x.
The endocrine effects of replacement doses of hydrocortisone in postmenopausal women with advanced breast cancer were compared with the same doses of hydrocortisone plus aminoglutethimide. Fifteen patients received aminoglutethimide (AG) 250 mg three times a day plus hydrocortisone (HC) 20 mg twice a day for 2 weeks, then AG was increased to 250 mg four times a day. Another 13 patients received HC alone for 2 weeks, then AG was added. HC alone significantly suppressed oestrone (75% of baseline) and oestradiol (50% of baseline). Addition of AG to these patients produced further oestrone suppression (50% of baseline) significantly greater than HC alone. HC alone suppressed dehydroepiandrosterone sulphate as much as AG + HC. delta 4-androstenedione (delta 4A) and dehydroepiandrosterone (DHA) were suppressed by HC alone. Addition of AG produced a rise of delta 4A to basal levels. These results show that 3-beta-ol de hydrogenase is not induced by AG. AG plus HC together from day 1 produced significantly greater oestrone suppression (50% of baseline) than HC alone. Because high-dose steroids may induce aromatase and replacement doses produced marked peripheral endocrine effects, the use of replacement hydrocortisone should be reassessed in advanced breast cancer.
将绝经后晚期乳腺癌患者使用氢化可的松替代剂量的内分泌效应,与相同剂量的氢化可的松加氨鲁米特的内分泌效应进行了比较。15名患者每天3次服用氨鲁米特(AG)250毫克加每天2次服用氢化可的松(HC)20毫克,持续2周,然后将AG增加至每天4次,每次250毫克。另外13名患者单独服用HC 2周,然后添加AG。单独使用HC可显著抑制雌酮(降至基线的75%)和雌二醇(降至基线的50%)。对这些患者添加AG后,雌酮进一步受到抑制(降至基线的50%),显著大于单独使用HC的效果。单独使用HC对硫酸脱氢表雄酮的抑制程度与AG + HC相同。单独使用HC可抑制δ4-雄烯二酮(δ4A)和脱氢表雄酮(DHA)。添加AG后,δ4A升高至基础水平。这些结果表明,AG不会诱导3-β-醇脱氢酶。从第1天起,AG加HC共同使用对雌酮的抑制作用(降至基线的50%)显著大于单独使用HC。由于高剂量类固醇可能诱导芳香化酶,且替代剂量会产生明显的外周内分泌效应,因此在晚期乳腺癌中应重新评估氢化可的松替代疗法的使用。