Adrenalectomy and hypophysectomy

Learning that the adrenal gland is a source of steroid production in postmenopausal women, surgical adrenalectomy as well as hypophy-sectomy (depriving ACTH) were considered treatment options for postmenopausal women (14, 15). At this time, the general belief was that postmenopausal estrogens together with androgens were synthesized and directly secreted by the adrenals; later, it was discovered that circulating androgens, mainly of adrenal but with a potential small contribution of testosterone from the postmenopausal ovaries (16-18), were converted into estrogens in different tissue compartments by the aromatase enzyme (Fig. 1), Both treatment options revealed significant antitumor effects but at considerable morbidity and even mortality. This led to the subsequent invention of "medical adrenalectomy" in an attempt to achieve similar antitumor effects at the cost of lower toxicity. However, treatment with glucocorticoids in moderate doses (prednisone/ prednisolone 5-10 mg daily) was associated with a low response rate, with similar results from trials exploring ketoconazole-derivatives specifically targeting 17-alpha-hydroxylase (see references and details in (19)).

A major breakthrough was achieved with the introduction of amino-glutethimide as treatment for metastatic disease. Due to toxic effects on the adrenocortical gland, the unsuccessful phenobarbitone antiepileptic aminoglutethimide was implemented aiming at achieving an effective "medical adrenalectomy" (20). While this drug was found to be a successful antitumor agent, the reason for its antitumour efficacy turned out to be potent inhibition of the aromatase enzyme (see below).

From PMS To PPD

From PMS To PPD

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