Acute effects of transdermal estrogen on hemodynamic and vascular reactivity in elderly postmenopausal healthy women

Abstract

OBJECTIVE: The acute effects of estrogen on hemodynamic responses were studied with emphasis on the sympathoadrenal system and peripheral circulation. DESIGN: Eleven healthy postmenopausal women recruited from the population-based study BEDA were included in this randomized, double-blind, cross-over, placebo-controlled hypothesis-generating pilot study, where the effect of transdermal estrogen (17 beta-estradiol, 100 microg/24 h) was tested. METHODS: Twenty-four hours after the patch with estrogen/placebo was attached, the blood pressure during rest and mental stress test was measured, together with blood samples for analysis of P-adrenaline and P-noradrenaline. Twenty-four-hour ambulatory registration of blood pressure and heart rate were recorded. Contractile properties and endothelial function of subcutaneous small arteries from gluteal biopsies were studied with the wire-myograph technique. RESULTS: Estrogen treatment reduced both ambulatory systolic blood pressure (5 mmHg, P = 0.05), diastolic blood pressure (3 mmHg, P < 0.05) and heart rate (6-8 beats/min during morning hours, P < 0.01). Diastolic blood pressure during and after mental stress was significantly reduced after estrogen treatment (p < 0.01). The levels of P-adrenaline and P-noradrenaline were similar in both treatment protocols. The contractile properties of the arteries were not significantly influenced by estrogen. Substance P induced nitric oxide-dependent relaxation in both estrogen-treated and placebo-treated precontracted arteries. Acetylcholine, on the other hand, induced a non-nitric oxide, non-prostanoid-dependent hyperpolarization, which was inhibited by potassium-induced depolarization after placebo but not after estrogen treatment. CONCLUSIONS: Acute administration of transdermal estrogen in clinically relevant doses modulates hemodynamics, probably by an altered parasympathetic balance, which might involve changes at the muscarinic receptor level.