The effect of flutamide on testosterone metabolism and the plasma levels of androgens and gonadotropins

The Journal of Clinical Endocrinology and Metabolism
L HellmanB Zumoff


Flutamide, a nonsteroidal antiandrogen, was given to 11 men with prostate cancer, in doses of 750 to 1500 mg daily for 0.5--7 months. Four patients had a clinical remission and seven showed no response. All the patients showed a profound change in the peripheral metabolism of testosterone: markedly increased conversion to androsterone (A) and correspondingly decreased conversion to etiocholanolone (E); the A/E ratio rose to levels never before observed consistently in any group of healthy or diseased humans. This change was probably due to alteration by flutamide of the relative activities of steroid 5alpha and 5beta reductase in favor of the former. 24-Hour mean plasma testosterone was increased in five of the six patients studied for this parameter, for the group as a whole, testosterone rose from 279 ng/dl to 484 ng/dl (P less than .05). 24-Hour mean values for plasma dihydrotestosterone, dehydroisoandrosterone, LH and FSH showed no significant change, for the group as a whole, in the same six patients. Since flutamide did not change the metabolic clearance rate or volume of distribution of testosterone tracers, the increased plasma levels of the hormone were probably due to increased production.


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Androgen Effect
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