Preservation of androgen secretion during estrogen suppression with aminoglutethimide in the treatment of metastatic breast carcinoma.
Preservation of androgen secretion during estrogen suppression with aminoglutethimide in the treatment of metastatic breast carcinoma.
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在转移性乳腺癌治疗中用氨鲁米特抑制雌激素期间保留雄激素分泌。
DOI：
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发表时间：
1980
影响因子：
15.9
通讯作者：
R. Santen
中科院分区：
文献类型：
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作者：
E. Samojlik;J. Veldhuis;S. Wells;R. Santen
我们评估了氨鲁米特 (AG) 对雄激素和雌激素水平的比较影响：雌酮（[E1]、雌二醇 [E2]、血浆硫酸脱氢表雄酮 [DHEA-S]、睾酮 [T]、二氢睾酮 [DHT]、δ 4-雄烯二酮 [δ 4-A]）、卵泡刺激素 (FSH)、黄体生成素绝经后乳腺癌患者的 LH 和催乳素被随机分配到 AG 治疗组或双侧肾上腺手术切除组作为对照组。无论哪种治疗，在 12 周的所有研究日中，血浆 E1 水平下降了 62-75%（P 小于 0.001），尿液 E1 水平下降了 85.7-88.7%（P 小于 0.001）。同样，血浆和尿液中 E2 的浓度下降了 40-72%，两种治疗方式之间没有统计学上的显着差异。在接受 AG 治疗的女性中，相对较弱的雄激素 DHEA-S 在 12 周时减少了 92%（877.3 +/- 184.6 至 71.8 +/- 14.5 ng/ml），但在肾上腺切除的女性中则抑制了近 99%（1,151 +/- 262 至 5.8 +/- 3.3 ng/ml）。在治疗后的所有时间点，接受 AG 的患者的 DHEA-S 水平均显着升高。在 AG 治疗期间，强效雄激素 T 和 DHT 的血浆浓度也相对保持不变。 AG 从未显着降低 T 水平，并且 DHT 浓度仅在第 4 周时降低至最大 20%。仅在治疗第 12 周，Delta 4-A 水平就下降了 56%（基础值，0.79 +/- 0.09 ng/ml；12 周，0.35 +/- 0.07 ng/ml）。与此形成鲜明对比的是，手术肾上腺切除术后，所有雄激素在每个时间段均显着下降，T 最大抑制率为 81%，DHT 最大抑制率为 73%，Delta 4-A 最大抑制率为 97%。作为对雌激素抑制的反应，两个治疗组在整个治疗期间血浆 FSH、LH 和催乳素水平均没有显着变化。为了检查绝经后卵巢对治疗期间激素水平的可能影响，分别评估了手术阉割和自然绝经妇女的数据。两组之间的 E1、E2、T、DHT、DHEA-S、delta 4-A、LH、FSH 和催乳素没有观察到显着差异。我们得出的结论是，尽管在 AG 治疗期间保留了雄激素分泌，但在手术肾上腺切除术后却没有保留雄激素分泌，但无论是 AG 还是手术肾上腺切除术，都会发生同等且高度显着的雌激素抑制。雌激素剥夺与雄激素保留相关的综合作用可能对 AG 对激素反应性肿瘤的治疗作用具有重要意义。
We evaluated the comparative effects of aminoglutethimide (AG) on androgen and estrogen levels estrone ([E1], estradiol [E2], plasma dehydroepiandrosterone-sulfate [DHEA-S], testosterone [T], dihydrotestosterone [DHT], delta 4-androstenedione [delta 4-A]), follicle-stimulating hormone (FSH), luteinizing hormone (LH), and prolactin in postmenopausal patients with breast cancer randomly allocated to either AG treatment or bilateral surgical adrenalectomy as a control group. In response to either treatment, the plasma levels of E1 fell 62-75% (P less than 0.001) and urine E1 85.7-88.7% (P less than 0.001) in all study days over a 12-wk period. Similarly, the concentrations of E2 in plasma and urine fell 40-72% without statistically significant differences between the two treatment modalities. The relatively weak androgen, DHEA-S, was reduced by 92% (877.3 +/- 184.6 to 71.8 +/- 14.5 ng/ml) at 12 wk in women treated with AG, but suppressed nearly 99% (1,151 +/- 262 to 5.8 +/- 3.3 ng/ml) in adrenalectomized women. At all time points after treatment, the DHEA-S levels were significantly higher in patients receiving AG. Plasma concentrations of the potent androgens, T and DHT, were also relatively preserved during AG treatment. T levels were never significantly reduced by AG, and DHT concentrations were decreased only at the 4th wk to a maximum of 20%. delta 4-A levels fell 56% in response to this drug only on the 12th wk of therapy (basal, 0.79 +/- 0.09 ng/ml; 12 wk, 0.35 +/- 0.07 ng/ml). In marked contrast, all androgens fell significantly at each time period in response to surgical adrenalectomy, with an 81% maximum suppression of T, 73% of DHT, and 97% of delta 4-A. In response to estrogen suppression, plasma levels of FSH, LH, and prolactin did not change significantly throughout the treatment period in either therapy group. To examine possible contributions of the postmenopausal ovary to hormone levels during therapy, data from surgically castrate and spontaneously menopausal women were evaluated separately. No significant differences between the two groups were observed for E1, E2, T, DHT, DHEA-S, delta 4-A, LH, FSH, and prolactin. We conclude that equivalent and highly significant estrogen suppression occurs with either AG or surgical adrenalectomy although androgen secretion is preserved during AG treatment but not after surgical adrenalectomy. The combined effects of estrogen deprivation associated with androgen preservation might be significant in the therapeutic action of AG in hormone-responsive neoplasms.