Aminoglutethimide was the first aromatase inhibitor to be used in breast cancer therapy but, since it interacts with the synthetic glucocorticoids, hydrocortisone must also be given as a replacement. The most important side-effects of aminoglutethimide are at the level of the central nervous system. Other aromatase inhibitors with greater potency and selectivity are being developed. Pyridoglutethimide, a compound resulting from modifications to the structure of aminoglutethimide, seems to be devoid of sedative properties according to preliminary tests on the central nervous system. 4-Hydroxyandrostenedione is significantly more potent and better tolerated than aminoglutethimide. Fadrozole (CGS 16 949 A) is 200 – 400 times more potent than aminoglutethimide and is now in phase II of its clinical development. CGS 20 267 has no effect on adrenal steroidogenesis and is currently in phase I of its clinical development. Availability of newer aromatase inhibitors could make a worthwhile contribution to endocrine therapy in breast cancer.
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