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 17 beta-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 17 beta-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.
Cardiology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892.
D M
DM
Gilligan
D M
DM
Badar
J A
JA
Panza
A A
AA
Quyyumi
R O
RO
Cannon
D000109:Acetylcholine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000494:pharmacology* / Q000627:therapeutic use; D015914:Estrogen Replacement Therapy; D004967:Estrogens / Q000172:deficiency; D005260:Female; D005542:Forearm / Q000098:blood supply*; D006801:Humans; D008875:Middle Aged; D009599:Nitroprusside / Q000494:pharmacology; D017698:Postmenopause / Q000187:drug effects / Q000502:physiology*; D014655:Vascular Resistance / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects*
D004967:Estrogens; D009599:Nitroprusside; D004958:Estradiol; D000109:Acetylcholine