Absence of Effects of Short‐Term Estrogen Replacement Therapy on Resting and Exertional QT and QT_c Dispersion in Postmenopausal Women with Coronary Artery Disease

Abstract

Women, on average, have a longer QT interval on the electrocardiogram and are at higher risk of developing torsade de pointes from antiarrhythmic therapy than men. Although endogenous estrogen may play a role in these sex differences, the effect of estrogen replacement therapy has not been examined. Ten women, 65 +/- 7 years of age, with stable angina pectoris, positive exercise test, and angiographically proven coronary artery disease (at least one > or = 70%) stenosis were studied. All women had been postmenopausal for at least 1 year, and none had ever received hormone replacement therapy (HRT). The patients received standard dose HRT (0.625 mg/day oral conjugated estrogen) or matching placebo for 4 weeks in random order, with crossover after a 4-week washout period. Exercise testing using the standard Bruce protocol was performed at the end of the first and third months of the study. Antianginal medications remained unchanged throughout the study period. Compared to placebo, HRT caused a significant increase in plasma estradiol levels from 5.55 +/- 1.66 to 31.11 +/- 14.95 pg/mL (P = 0.001). QT and QTc, as well as QT and QTc dispersion, did not differ at rest and at peak exercise between the two exercise tests. Likewise, other test results, including angina score, exercise time, ST-T changes, blood pressure, heart rate, and double product were unchanged. Short-term HRT did not alter cardiac repolarization at rest and during exercise in postmenopausal women with known coronary disease.

Long term effects of hormone replacement therapy on heart rate variability, QT interval, QT dispersion and frequencies of arrhytmia

“…Unopposed estrogen in conventional doses administered orally in a short term in women with known coronary artery disease had no effects on QT and QTc both at rest and on exercise in one study [17]. Likewise, acute administration of supraphysiological doses of estrogen in healthy women produced no significant changes in QT and QTc intervals, whereas both QT and QTc prolonged significantly in women with syndrome X [30].…”

“…Sbarouni et al [17] investigated the effects of a conventional 4-week estrogen replacement therapy on rest and exercise QT intervals and QT dispersion in 10 patients with coronary artery disease. In this study , Sbarouni et al demonstrated that no significant differences between estrogen treated and placebo groups with respect to QT values.…”

“…In this context of increased arrhytmic risk in females, it is of interest that estrogens and tamoxifen, the classical estrogen receptor antagonist have been shown to modulate the electrophysiological properties of myocytes [14 -16]. However, estrogen replacement therapy (ERT) in postmenopausal women for one month did not change the myocardial repolarization determined by analysis of QT interval length and QT dispersion [17], and no differences in QT interval length have been reported during HRT [18].…”

Gender differences in ventricular arrhythmia recurrence in patients with coronary artery disease and implantable cardioverter-defibrillators

“…Experimentally, estrogen affects potassium-channel protein synthesis, which alters repolarization (31) and can increase atrial refractory periods (32). However, studies of hormone replacement therapy in postmenopausal women (33) and of cyclical changes in premenopausal women (34) have not shown an influence of circulating estrogens on repolarization. Testosterone alters potassium currents in patch-clamp experiments (35) and alters the QT interval in castrated men (36).…”

Effects of Long-Term Hormone Replacement Therapy on QT and Corrected QT Dispersion during Resting and Peak Exercise Electrocardiography in Post-Menopausal Women.

“…Only one study performed up to now, which investigated the effects of HRT during peak exercise, indicated that HRT did not affect the QT parameters during resting and exercise in postmenopausal women with coronary artery disease. 15) In the study, the results of one month therapy were evaluated and HRT was administered only with estrogen.…”