Does sublingual 17β-oestradiol have any effects on exercise capacity and myocardial ischaemia in post-menopausal women with stable coronary artery disease?

Abstract

Background: A variety of vascular effects have been ascribed to 17β-oestradiol. These effects explain the reduced incidence of disease found in post-menopausal replacement therapy. Objectives: To evaluate the effects of 2 mg sublingual 17β-oestradiol on exercise capacity, exercise-induced myocardial ischaemia and circulating levels of endothelin-1 in post-menopausal women with stable coronary artery disease. Methods: Twelve pest-menopausal women, mean age 61 (range 52-72) years, with angiographically verified significant coronary artery disease, were randomly assigned to 2 mg of sublingual 17β-oestradiol, 2.5 mg of buccal nitroglycerine and to placebo in a double-blind cross-over study design with at least 2 days between each of the study arms. Antianginal medications, with the exception of betablockers, were discontinued before investigation. All study patients underwent a maximal bicycle exercise test 30 min after drug intake. Blood was withdrawn immediately before and up to 8 h after medication for analyses of circulating levels of oestradiol and endothelin-1. Results: The mean serum levels of oestradiol increased from a control level of 72 ± 28 pmol.l-1 to 3557 ± 1631 pmol.l-1 after 30 min and to 5028 ± 3971 pmol.l-1 after 60 min with a gradual decline thereafter. Sublingual 17β-oestradiol did not induce any improvement in exercise duration when compared with nitroglycerin and placebo (500 ± 112 s, 505 ± 107 s, 498 ± 157 s), and did not influence time to onset of ST-segment depression (358 ± 89 s, 436 ± 93 s, 384 ± 116 s). The plasma levels of endothelin-1 did not change after administration of 17β-oestradiol, nitroglycerin or placebo. Conclusions: No effects on exercise capacity, exercise-induced acute ischaemia, or plasma levels of endothelin-1 were found after a single dose of 2 mg 17β-oestradiol in post-menopausal women with documented coronary artery disease.