Effects of oral and transdermal estrogen replacement therapy on markers ofcoagulation, fibrinolysis, inflammation and serum lipids and lipoproteins in postmenopausal women

We compared the effects of oral estradiol (2 mg), transdermal estradiol (50 mug), and placebo on measures of coagulation, fibrinolysis, inflammation a nd serum lipids and lipoproteins in 27 postmenopausal women at baseline and after 2 and 12 weeks of treatment. Oral and transdermal estradiol induced similar increases in serum free estradiol concentrations. Oral therapy incr eased the plasma concentrations of factor VII antigen (FVIIag) and activate d factor VII (FVIIa), and the plasma concentration of the prothrombin activ ation marker prothrombin fragment 1+2 (F1+2). Oral but not transdermal estr adiol therapy significantly lowered plasma plasminogen activator inhibitor- 1 (PAI-1) antigen and tissue-type plasminogen activator (tPA) antigen conce ntrations and PAI-I activity, and increased D-dimer concentrations, suggest ing increased fibrinolysis. The concentration of soluble E-selectin decreas ed and serum C-reactive protein (CRP) increased significantly in the oral b ut not in the transdermal or placebo groups. In the oral but not in the tra nsdermal or placebo estradiol groups low-density-lipoprotein (LDL) choleste rol, apolipoprotein Band lipoprotein (a) concentrations decreased while hig h-density-lipoprotein (HDL) cholesterol; apolipoprotein AI and apolipoprote in All concentrations increased significantly. LDL particle size remained u nchanged. In summary, oral estradiol increased markers of fibrinolytic acti vity, decreased serum soluble E-selectin levers and induced potentially ant iatherogenic changes in lipids and lipoproteins. In contrast to these benef icial effects, oral estradiol changed markers of coagulation towards hyperc oagulability, and increased serum CRP concentrations. Transdermal estradiol or placebo had no effects on any of these parameters. These data demonstra te that oral estradiol does not have uniformly beneficial effects on cardio vascular risk markers and that the oral route of estradiol administration r ather than the circulating free estradiol concentration is critical for any changes to be observed.