Danazol and its principal metabolites interfere with binding of testosterone, cortisol, and thyroxin by plasma proteins

Abstract

Danazol and its three principal metabolites (2-hydroxymethylethisterone, 2-hydroxymethyl-1,2-dehydroethisterone, and ethisterone) competitively displace cortisol and testosterone from plasma proteins. The effect is in addition to the reported inhibition of the production of testosterone-binding globulin and thyroxin-binding globulin. We saw no competitive inhibition of thyroxin binding. Concentrations of total testosterone, total cortisol, and total thyroxin were low, whereas percentages of free testosterone, free cortisol, and free thyroxin were abnormally high in women being treated with danazol. Values for testosterone, cortisol, and thyroxin in danazol-treated patients should therefore be appropriately corrected before interpretation. Protein-binding assays for testosterone or cortisol that involve testosterone- or cortisol-binding globulin may be invalid in danazol-treated subjects because of the competitive binding of danazol and its metabolites to these proteins.