Isolation of Urinary Metabolites of 1 ?a-Methyltestosterone*

Methyltestosterone (17ar-methyl-17/3-hydroxyandrost-4-ene-3one) is an androgen which is orally effective and has had wide clinical use. We have treated patients with methyltestosterone for their advanced breast cancer (1). The compound led to a substantial decrease in urinary gonad-stimulating hormone similar to that seen after the parenteral administration of testosterone propionate. However, unlike testosterone propionate, methyltestosterone did not increase the urinary 17ketosteroid excretion. Instead, it produced an increase in pregnanediol chromogen that was proportionate to the amount of methyltestosterone administered. Previous work by Levedahl and Samuels (2) indicated that 17a-methyltestosterone was not converted in vitro to 17-ketosteroids by dog, rat, rabbit, or human livers, whereas ring A was metabolized. Van Stewart and Samuels (3) demonstrated that CF-17ar-methyltestosterone was metabolized in vitro to 17amethylandrost&ene-3a(, 17/?-diol by a cell-free rat liver preparation. This lack of knowledge concerning the fate of methyltestosterone stimulated our interest in the metabolism in vivo of methyltestosterone by man.