Effects of norethisterone on coagulation and fibrinolysis in Asian women.

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 levels were decreased (P<0.01). Prothrombin increased significantly (P<0.001) at the initial 3 months medication after which it gradually reverted to baseline values at 9 months. Factors 5 and 10 were significantly increased throughout the period of therapy (P<0.001) while factor 8 showed no change. This is evidence that coagulation factors from the liver were affected by norethisterone while that from the vascular endothelium is not. The coagulation changes in factors resulted in a shortened prothrombin time and kaolin cephalin time in the initial period of treatment reflecting the initial increase in prothrombin. Jaundice occurred in 3 patients when their prothombin levels were at their highest for the individual patient. The adjustment and return to baseline level did not occur in jaundiced patients although this time was the trend in the others. Fibrinolytic activity as shown by the fibrin plate test was not changed nor was antithrombin 3 activity or the levels of fibrinogen/fibrin degradation product. The cellular components of blood in patients treated with norethisterone was affected. The packed volume cell 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 treatments and to monitor its effect during treatment. This would apply to all patients to be given norethisterone whether it be at low doses or especially at high doses. This is due to the unpredictable effect of the drug on liver metabolism. 2 patients who became jaundiced had 20 mg norethisterone/day for 3 months which was a comparatively low dosage in this study. Results of this study should be considered when norethisterone is being contemplated for contraceptive use especially in Asian women since they are more prone to liver diseases. (authors modified)