Estradiol supplementation suppresses hyperventilation-induced attacks in postmenopausal women with variant angina

OBJECTIVES We sought to examine whether estradiol (E2) supplementation suppresses anginal attacks in women with variant angina. BACKGROUND Estrogen is known to improve endothelial function. Coronary spasm plays an important role in the pathogenesis of not only variant angina but also ischemic heart disease in general, and endothelial dysfunction seems to be involved in the pathogenesis of coronary spasm. METHODS Fifteen postmenopausal women with variant angina (mean age 54.2 years) were given a hyperventilation (HV) test, a provocation test for coronary spasm, in the early morning of day 1 (baseline), day 3 (after 2-day transdermal E2supplementation, 4 mg) and day 5 (after 2-day placebo administration). We measured the flow-mediated (endothelium-dependent) dilation (FMD) of the brachial artery with the ultrasound technique before each HV test. RESULTS The anginal attacks with ST segment elevation were induced by HV in all patients on days 1 and 5. However, no attacks were induced on day 3. Supplementation with E2augmented FMD (3.5 ± 0.6∗, 8.9 ± 0.7 and 4.0 ± 0.5∗ on days 1, 3 and 5, respectively; ∗p < 0.01 vs. day 3). The serum E2levels on days 1, 3 and 5 were 22.7 ± 2.8∗, 96.2 ± 9.2 and 30.7 ± 7.1∗ pg/ml, respectively (∗p < 0.01 vs. day 3). CONCLUSIONS The present results demonstrated for the first time, to our knowledge, that E2supplementation suppresses the HV-induced attacks in women with variant angina, in part because of the improvement of endothelial function.