Effects of oral and transdermal estrogen replacement therapy on markers of coagulation, fibrinolysis, inflamation and serum lipids and lipoproteins in postmenopausal women.Thromb

Background—We determined whether the vascular effects of estradiol depend on the route of administration by comparing the effects of oral estradiol and transdermal placebo, transdermal estradiol and oral placebo, and transdermal placebo and oral placebo on in vivo endothelial function in 27 postmenopausal women. Methods and Results—Endothelial function was assessed from blood flow responses to intrabrachial artery infusions of endothelium-dependent (7.5 and 15 mg/min acetylcholine) and endothelium-independent (3 and 10 mg/min of sodium nitroprusside) vasodilators at 0, 2, and 12 weeks. In the oral estradiol group, the increase in flow above basal during infusion of the low dose of acetylcholine at 0, 2, and 12 weeks averaged 6.060.8, 6.960.8, and 11.361.2 (P,0.01 versus 0 and 2 weeks) mL z dL21 z min21 at 0, 2, and 12 weeks. The percentage increases versus 0 weeks averaged 21614 % at 2 and 120634 % at 12 weeks. During the high-dose acetylcholine infusion, the increase in flow above basal averaged 8.661.3, 10.261.5, and 15.161.8 (P,0.05 versus 0 weeks) mL z dL21 z min21, respectively. The percentage increases versus 0 weeks averaged 22610 % at 2 weeks and 119646 % at 12 weeks. In the oral estradiol group, endothelium-independent vasodilatation also improved significantly, but less markedly than endothelium-dependent responses. In the transdermal and placebo groups, all vascular responses remained unchanged. Oral but not transdermal estradiol also induced significant decreases in LDL cholesterol and Lp(a) concentrations and an increase in HDL cholesterol within 2 weeks