Effects of low-dose oral and transdermal estrogen replacement therapy on hemostatic factors in healthy postmenopausal women: A randomized placebo-controlled study

Objective This study was undertaken to investigate the effect of transdermal and oral estrogen replacement therapy in healthy postmenopausal women on markers of coagulation and fibrinolysis associated with coronary artery disease. Study design In a randomized, placebo-controlled, double-blind study, healthy hysterectomized postmenopausal women received daily either placebo (n = 49), transdermal 17β-estradiol (E2) 50 μg (tE2 group, n = 33), oral E2 1 mg (oE2 group, n = 37), or oral E2 1 mg combined with gestodene 25 μg (oE2 + G group, n = 33) for thirteen 28-day treatment cycles. Hemostatic variables were measured in blood samples collected at baseline and in cycles 4 and 13. Results No significant changes versus baseline and placebo were found in the tE2 group, except for plasminogen activator inhibitor type-1 (PAI-1) in cycle 13 (−32.4%, P = .01). In the oE2 group, significant percentage changes from baseline versus placebo in cycle 13 were found in fibrinogen, −5.4% (P<.05); factor VII, −7.3% (P<.05); thrombin-antithrombin III complexes, −13.3% (P<.05); tissue-type plasminogen activator (t-PA), −17.3% (P<.001); and PAI-1, −54.3% (P<.001). In the oE2 + G group, respective changes were factor VII, −17.6% (P<.001); t-PA, −14.5% (P = .01); PAI-1, −36.4% (P<.01); and D-dimer, +21.8% (P<.05). No significant changes were observed in prothrombin fragment 1 + 2 and plasmin-α2-antiplasmin complexes. Conclusion Low-dose oral estradiol therapy was associated with an increase in fibrinolysis and small decreases in procoagulant variables. Transdermal therapy had minor effects.