Steroid hormone profiles in women treated with aminoglutethimide for metastatic carcinoma of the breast.

Recent evidence suggests that aminoglutethimide (AG), a known inhibitor of adrenal steroidogenesis, is a potent blocker of aromatase and thus of estrogen production. These properties of AG have been exploited clinically to reduce the biosynthesis of adrenal estrogen precursors and extraglandular estrogen production in postmenopausal women with metastatic breast carcinoma. In this study, we have explored the effects of AG on a variety of steroids, including delta 5-C19 and -C21 compounds and delta 4-C19 and -C21 steroids as well as plasma and urinary estrogens in a series of postmenopausal women with breast cancer treated for 2 to 26 weeks. Plasma concentrations of delta 5-C21 and -C19 compounds were reduced 3- to 5-fold during AG therapy and remained suppressed over the duration of the study. By contrast, the delta 4-steroids such as progesterone, androstenedione, and 17 alpha- hydroxyprogesterone rose 2- to 10-fold during the initial 2 weeks of AG treatment and then fell back to starting levels or were suppressed. Plasma levels of the potent androgens testosterone and dihydrotestosterone were relatively preserved during AG therapy. The possible contribution of the postmenopausal ovary to the above hormone levels during AG therapy was examined by comparing steroid values from surgically castrated and spontaneously menopausal women. No statistically significant differences between the two groups were observed. In response to AG therapy, plasma levels of estrone and estrone sulfate were decreased 61 to 72%, and urinary estrone similarly fell 85% over the 12-week period. Estradiol concentrations in urine and plasma were similarly reduced 40 to 66% from basal values over this same period.