Estrogen and Progestin Use and the QT Interval in Postmenopausal Women

Abstract

These results suggest that unopposed estrogen in menopausal women mildly prolongs myocardial repolarization, and the effect is reversed by progesterone. Whether these findings have clinical significance requires further study.

New Aspects for the Treatment of Cardiac Diseases Based on the Diversity of Functional Controls on Cardiac Muscles: Acute Effects of Female Hormones on Cardiac Ion Channels and Cardiac Repolarization

“…As regards to the increased female hormone levels during pregnancy, the risk of TdP in congenital LQTS patients is significantly decreased during pregnancy, although cardiac events are increased postpartum, suggesting the involvement of changes in serum female hormone levels (31). In post-menopausal women, although earlier studies reported conflicting findings regarding the effects of HRT on QT C interval (17), a recent study with a large study population indicated that HRT with estrogen alone causes slight but significant prolongation of the QT C interval, while the combination of HRT with estrogen and progestin consistently shortens this interval (27). Collectively, these clinical findings suggest the tempting hypothesis that the luteal hormone progesterone shortens the duration of ventricular depolarization by regulating cardiac ion channels.…”

“…In females, there are dynamic fluctuations in QT interval and TdP risk during the menstrual cycle and pregnancy, which may correlate with changes in serum levels of ovarian steroids (3). Several studies have evaluated the potential impact of hormone replacement therapy (HRT) on QT C intervals in postmenopausal women (17,27). Although conflicting findings exist regarding HRT, these clinical findings imply that the dynamic changes in levels of female hormones have cyclical effects on action potential duration (APD).…”

“…Regarding effects on cardiac repolarization, although there are conflicting findings regarding the effects of estrogen on QT C intervals in women, a recent large-scale clinical study of post-menopausal women revealed very slight, but significant, QT C prolongation by a few milliseconds with estrogen-replacement menopausal therapy alone (27). Because QT C prolongation in women currently taking estrogen-only HRT is statistically significant compared with that in women with previous use of HRT (27), exogenous estrogen may affect cardiac repolarization in a reversible fashion, suggesting the existence of acute effects of estrogen.…”

“…Because QT C prolongation in women currently taking estrogen-only HRT is statistically significant compared with that in women with previous use of HRT (27), exogenous estrogen may affect cardiac repolarization in a reversible fashion, suggesting the existence of acute effects of estrogen. This clinical evidence suggests that acute effects of estrogen are likely to underlie the dynamic fluctuation in druginduced QT C prolongation and arrhythmia development during the menstrual cycle (28), in turn suggesting the contribution of non-transcriptional, 'acute' effects of Fig.…”

A Receptor-Independent Effect of Estrone Sulfate on the hERG Channel

“…In healthy premenopausal women volunteers, the susceptibility of drug-induced QT C prolongation is exaggerated in the late follicular phase where estrogen level is the highest (8). Baseline QT C in postmenopausal women who are currently taking an only estrogen-replacement therapy is slightly but significantly longer compared with the control population (9). In addition to the well-characterized influences of estrogen in cardiac repolarization concerning hormonal genomic actions (1, 10), we recently found that the physiological levels of 17β-estradiol (E2), the bioactive estrogen, acutely downregulates the hERG channel, resulting in QT C prolongation (11).…”