Effects of estrogen replacement therapy on peripheral vasomotor function in postmenopausal women

Hormone replacement therapy is associated with a reduction in cardiovascular events in postmenopausal women. We have recently found that acute 17β-estradiol administration improves endothelium-dependent vasodilation in both the peripheral and coronary circulations of postmenopausal women. The current study was undertaken in 33 estrogen-deficient postmenopausal women (mean age 59 ± 7 years) to determine if short-term estrogen replacement therapy also improves endothelium-dependent vasodilation in peripheral circulation. Acute intraarterial infusion of estradiol, which increased forearm venous estradiol levels from 16 ± 11 to 345 ± 202 pg/ml, potentiated forearm vasodilation induced by the endothelium-dependent vasodilator acetylcholine by 49 ± 67% (p <0.001). Acute estradiol also potentiated vasodilation induced by the endothelium-independent vasodilator nitroprusside by 5 ± 31% (p = 0.04). However, after 3 weeks of transdermal estradiol administration (0.1 mg/day), which achieved an estradiol level of 120 ± 57 pg/ml, the vasodilator responses to acetylcholine and to sodium nitroprusside were unchanged from initial measurements obtained before acute administration of estradiol. Repeat intraarterial infusion of estradiol in 8 women, while receiving transdermal estradiol, increased forearm venous estradiol levels to 268 ± 105 pg/ml and again potentiated the vasodilator response to acetylcholine to a similar degree as that observed in the initial study after acute administration of estradiol. Thus, although acute intraarterial infusion of 17β-estradiol potentiates endothelium-dependent vasodilation in the forearms of postmenopausal women, this effect is not maintained with a 3-week cycle of systemic estradiol administration. The different effects of acute and chronic estradiol may be due to the lower plasma levels achieved with chronic estrogen administration.