Vermeulen A, Paridaens R, Heuson J C
Clin Endocrinol (Oxf). 1983 Dec;19(6):673-82. doi: 10.1111/j.1365-2265.1983.tb00044.x.
Effects of various doses of aminoglutethimide (AG) alone upon adrenal steroidogenesis were studied in normal postmenopausal women, whereas the effects of combined treatment with aminoglutethimide in variable doses together with 40 mg of hydrocortisone were studied in postmenopausal women with advanced mammary cancer and compared to effects of treatment with cortisol alone. Despite the well known inhibitory effect of AG on cortisol biosynthesis, plasma cortisol levels were unaffected by AG in doses of 150-1000 mg/d, probably due to a compensatory increase in ACTH in subjects with an intact pituitary-adrenal axis. The aromatase system appeared to be very sensitive to inhibition by AG, a clearcut inhibition being shown at doses as low as 150 mg/d. Evaluated from the ratio of plasma oestrone (E1) to plasma androstenedione (AN), treatment with AG at a dose of 150 mg/d appeared to reduce the aromatase activity to 33% of the basal value; 250 mg/d resulted in a reduction to 20% and 1 g/d to 5% of basal values. Whereas AG at 150 mg/d did not appear to affect 11 beta-hydroxylase, the latter was clearly inhibited by 250 mg/d and even more so by 1000 mg/d, as indicated by the increase in plasma 11-desoxycortisol and 17-OH progesterone (17-OHP) levels. Due to the increase of the latter, their biosynthetic precursor, AN and to a lesser degree testosterone (TS) levels increased significantly during AG treatment at a dose of 250 or 1000 mg/d. delta 5 steroid levels remained practically unchanged, probably because 11-(as well as the 21-) hydroxylation concerns essentially the delta 4 pathway. During combined treatment with 500-1000 mg/d of AG and cortisol 40 mg/d, AN and TS were significantly higher than during treatment with cortisol alone, suggesting that cortisol had not completely blocked ACTH secretion. E1 and E2 levels were however lower than during treatment with cortisol alone, a consequence of the inhibition of the aromatase activity. Although at a dose of 500-1000 mg/d AG is a highly effective aromatase inhibitor, oestrogen levels during treatment with AG with or without concomitant administration of cortisol are still significantly different from zero. Therefore if one aims at complete elimination of any oestrogen effect, addition of an antioestrogen to AG treatment may be required.
在正常绝经后女性中研究了不同剂量的氨鲁米特（AG）单独对肾上腺类固醇生成的影响，而在晚期乳腺癌绝经后女性中研究了不同剂量的氨鲁米特与40mg氢化可的松联合治疗的效果，并与单独使用皮质醇治疗的效果进行了比较。尽管AG对皮质醇生物合成有众所周知的抑制作用，但150 - 1000mg/d剂量的AG对血浆皮质醇水平无影响，这可能是由于垂体 - 肾上腺轴完整的受试者中促肾上腺皮质激素（ACTH）代偿性增加所致。芳香化酶系统似乎对AG的抑制非常敏感，低至150mg/d的剂量就显示出明显的抑制作用。从血浆雌酮（E1）与血浆雄烯二酮（AN）的比值评估，150mg/d剂量的AG治疗似乎将芳香化酶活性降低至基础值的33%；250mg/d导致降低至20%，1g/d降低至基础值的5%。虽然150mg/d的AG似乎不影响11β - 羟化酶，但250mg/d时该酶明显受到抑制，1000mg/d时抑制更明显，这可从血浆11 - 脱氧皮质醇和17 - 羟孕酮（17 - OHP）水平升高看出。由于后者增加，其生物合成前体AN以及程度较轻的睾酮（TS）水平在250或1000mg/d剂量的AG治疗期间显著升高。δ5类固醇水平基本保持不变，可能是因为11 - （以及21 - ）羟化主要涉及δ4途径。在500 - 1000mg/d的AG与40mg/d皮质醇联合治疗期间，AN和TS显著高于单独使用皮质醇治疗期间，这表明皮质醇并未完全阻断ACTH分泌。然而，E1和E2水平低于单独使用皮质醇治疗期间，这是芳香化酶活性受到抑制的结果。尽管500 - 1000mg/d剂量的AG是一种高效的芳香化酶抑制剂，但无论是否同时给予皮质醇，AG治疗期间的雌激素水平仍显著不同于零。因此，如果旨在完全消除任何雌激素效应，可能需要在AG治疗中添加抗雌激素药物。
