Resistance of the ovary to blockade of aromatization with aminoglutethimide.

Aminoglutethimide (AG) is a potent inhibitor of aromatization in placental microsomes and in peripheral tissues in postmenopausal women. Aromatase inhibitors have been used to block estrogen production and induce breast tumor regression in rodents. To inhibit ovarian estrogen production, we administered various doses of AG and its highly potent D-stereoisomer to premenopausal women with breast carcinoma. However, at no dose level did AG consistently lower estrone and estradiol concentrations in plasma below those observed in normal menstruating women. Uniform increments in LH and FSH were also not observed. Only during the luteal phase were the levels of estradiol (but not estrone) significantly suppressed. These observations are best explained by the possibility that aromatase enzymes in the ovary, as opposed to those in the placenta and in peripheral tissues, are partially resistant to the effects of AG.