Beneficial effects of postmenopausal hormone replacement therapy with transdermal estradiol on sensitivity to activated protein C

Many hemostatic and fibrinolytic parameters have been evaluated following h ormone replacement therapy (HRT) but little is known about its influence on the anticoagulant response to activated protein C (APC-sensitivity). For t his purpose, we studied the effect of transdermal 17-beta-estradiol (50 mu g/24 h) by a continuous regimen on the APC-sensitivity, in 28 postmenopausa l hysterectomized women (mean age, 47 years; range, 44-65 years), We also m easured the plasma proteins directly involved in the protein C anticoagulan t pathway, such as activities of factor VIII (VIII:C), factor V and free pr otein S. Von Willebrand factor (vWF) antigen, the carrier protein of factor Vm, was also determined, Blood sampling was done at baseline and after 16- week therapy. A significant increase in the normalized AFC-sensitivity rati o (n-APC-SR) values (mean +/- SD: pre-trial, 0.88 +/- 0.14; post-trial, 1.0 1 +/- 0.12; P < 0.001) and a significant decrease of factor Vm:C plasma lev els (pre-trial, 1.13 +/- 0.29 IU/ml; post-trial, 0.98 +/- 0.20 IU/ ml; P = 0.001) were found. No difference was observed in factor V, protein S and VW F plasma levels. Correlation studies demonstrated only a significant negati ve correlation between the percent change in n-APC-SR and the percent chang e in factor VIII:C (r = -0.574; P = 0.001). Our findings clearly show that HRT with transdermal estradiol improves the anticoagulant response to APC, probably as a result of a decreased factor VIII:C. We also suggest that a s imilar but opposite mechanism may occur for perorally administered estrogen s used in the HRT. These results may have some clinical implications about the reported increase of the risk for venous thromboembolism following HRT. Blood Coag Fibrinol 11:175-182 (C) 2000 Lippincott Williams & Wilkins.