Short-term oral administration effects of danazol and estrogens on the von Willebrand factor

Danazol, an attenuated androgen, is reported to raise plasma levels of clotting factor VIII (F.VIII) in hemophilic patients, but no effects on the von Willebrand factor (vWF) have been studied. plasma, F. VIII and vWF are combined to form the complex VIII/vWF. Increased vWF levels in plasma are suspected to be a factor inducing arteriosclerosis, and unusually large vWF multimers or elevated vWF were observed in patients with thrombotic thrombocylopenic purpura and pregnancy-induced hypertension. Since danazol has been widely used for treatment of endometriosis, we studied the effect of danazol on vWF following a short-term oral administration (3 weeks), and then compared results with conjugate estrogens which are known to stimulate the biosynthesis of vWF in the vascular endothelial cells. Both danazol and conjugated estrogens similarly increased the vWF plasma levels in the first week, followed by a gradual decrease, and then returned to the initial levels by the end of the administration. In addition, multimeric analysis iff vWF showed no unusually large vWF multimers. Danazol has the same effect with the conjugated estrogens to the plasma level of vWF, not leading to sustained high levels in vWF antigen, therefore the long term usage may be safe.