SUPPRESSION OF RESIDUAL OESTROGEN PRODUCTION WITH AMINOGLUTETHIMIDE IN WOMEN FOLLOWING SURGICAL HYPOPHYSECTOMY OR ADRENALECTOMY

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Abstract
In postmenopausal women with breast carcinoma, plasma and urinary estrogens remain detectable following adrenalectomy or hypophysectomy. These residual estrogens could result from absorption of exogenous steroids, from endogenous production or both. To determine whether endogenous production contributes to this estrogen pool, a potent steroidogenesis inhibitor, aminoglutethimide (AG), was administered to women with breast carcinoma following hypophysectomy or adrenalectomy. Plasma and urinary estrogens were measured using radioimmunoassays. In 5 women treated after initial hypophysectomy (hypox), plasma estrone fell from 66 .+-. 28 pg/ml (hypox) to 9.1 .+-. 2.4 pg/ml (hypox and AG), and estradiol decreased from 8.3 .+-. 1.8 pg/ml to 2.5 .+-. 0.69 pg/ml. Similar decrements in urine estrone (U-E1) and estradiol (U-E2) were observed (U-E1 hypox: 2.25 .+-. 0.71 .mu.g/24 h and 0.071 .+-. 0.015 .mu.g/24 h hypox and AG; U-E2 0.47 .+-. 0.12 .mu.g/24 h hypox to 0.124 .+-. 0.015 hypox and AG, P < 0.05 for all). Similar significant reductions in plasma estrone and estradiol were observed in 4 women treated with AG following surgical adrenalectomy. While the levels of urinary estrogens also fell in these patients, the differences were not statistically significant. In response to the decrements in estrogen levels induced by AG, 2/5 women in the posthypophysectomy group and 2/4 in the postadrenalectomy group experienced partial objective tumor regression. Endogenous production of estrogens in extragonadal and extraadrenal sites apparently occurs after major surgical endocrine ablation in women with breast carcinoma. Additional exogenous estrogen sources cannot be excluded.