Differential effects of oral and transdermal estrogen replacement therapy on endothelial function in postmenopausal women

Background-We determined whether the vascular effects of estradiol depend o n the route of administration by comparing the effects of oral estradiol an d transdermal placebo, transdermal estradiol and oral placebo, and transder mal placebo and oral placebo on in vivo endothelial function in 27 postmeno pausal women. Methods and Results-Endothelial function was assessed from blood flow respo nses to intrabrachial artery infusions of endothelium-dependent (7.5 and 15 mug/min acetylcholine) and endothelium-independent (3 and 10 mug/min of so dium nitroprusside) vasodilators at 0, 2, and 12 weeks. In the oral estradi ol group, the increase in flow above basal during infusion of the low dose of acetylcholine at 0, 2, and 12 weeks averaged 6.0+/-0.8, 6.9+/-0.8, and 1 1.3+/-1.2 (P<0.01 versus 0 and 2 weeks) mt.dL(-1).min(-1) at 0, 2, and 12 w eeks. The percentage increases versus 0 weeks averaged 21+14% at 2 and 12034% at 12 weeks. During the high-dose acetylcholine infusion, the increase in flow above basal averaged 8.6+1.3, 10.2+/-1.5, and 15.1+/-1.8 (P<0.05 ve rsus 0 weeks) mL.dL(-1).min(-1), respectively. The percentage increases ver sus 0 weeks averaged 22+/-10% at 2 weeks and 119+/-46% at 12 weeks. In the oral estradiol group, endothelium-independent vasodilatation also improved significantly, but less markedly than endothelium-dependent responses. In t he transdermal and placebo groups, all vascular responses remained unchange d. Oral but not transdermal estradiol also induced significant decreases in LDL cholesterol and Lp(a) concentrations and an increase in HDL cholestero l within 2 weeks. Conclusions-We conclude that oral but not transdermal estradiol induces pot entially antiatherogenic changes in in vivo endothelium-dependent vasodilat ation and lipid concentrations.