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Aromatase is an enzyme which catalyses three hydroxylations which are necessary for the metabolism of steroidal hormones from cholesterol. It is present in great quantities in the adrenal gland and ovaries, and most probably in other tissues (present in mammary cells).

Aminoglutethimide acts in the same manner as chemical adrenalectomy, i.e. blocks the synthesis of minor androgens and oestrogens by the adrenal gland. It also disturbs the synthesis of hydrocortisone, thus, in order to avoid Addison’s disease, small doses of hydrocortisone should be simultaneously administered.

Blockade of synthesis by aminoglutethimide

In breast cancer, the response rate (as second-line hormonotherapy) is approximately 20-30%. In prostate cancer, the same indication gives a response rate of around 15-20%.

Diagram of the action of a classical antiaromatase on prostate cancer: aminoglutethimide

The above diagram clearly shows that, in prostate cancer, the main source of testosterone remains unaltered by aminoglutethimide and that castration (either surgical or medical) should be continued in order to avoid a rebound effect.