Effects of norethisterone on coagulation and fibrinolysis in Asian women

Abstract

High doses of norethisterone in 70 Asian women treated for endometriosis were found to affect the blood coagulation factors as well as the cellular components of the blood. Fibrinogen level was found to be decreased (p < 0.01). Prothrombin increased significantly (p < 0.001) during the initial three months' medication, after which it gradually reverted to baseline values at nine months. Factor V and X were significantly increased throughout the period of therapy (p<0.001) whilst factor VIII showed no change. This is evidence that coagulation factors from the liver are affected by norethisterone whilst that from the vascular endothelium is not. The changes in coagulation factors resulted in a shortened prothrombin time and kaolin cephalin time in the initial period of treatment reflecting the initial increase in prothrombin level. Jaundice occurred in three patients when their prothrombin levels were at their highest for the individual patient. The adjustment and return baseline levels did not occur in jaundiced patients although this was the trend in the other patients. Fibrinolytic activity as shown by the fibrin plate test was not changed; neither was the antithrombin III activity or the levels of fibrinogen/fibrin degradation product. The cellular components of blood in patients treated with norethisterone were affected. The packed cell volume and platelet numbers were increased. This may be an androgenic effect of norethisterone. Since the effect of norethisterone on coagulation factors is mainly via the effect of this progestogen in high doses on the liver, it would seem prudent to exclude liver dysfunction and previous liver disease before embarking on such treatment, and to monitor its effect during treatment. This would apply to all patients given norethisterone whether it be at low dose or especially at high doses. This is because of the unpredictable effect of the drug on liver metabolism. Two patients who became jaundice had 20 mg norethisterone per day for three month which was a comparatively low dose in this study. The results of this study should be considered when norethisterone is being contemplated for contraceptive use especially in Asian women, since they are known to be more prone to liver disease.