Effects of hormone replacement therapy on QT interval

Larsen, Jennifer A.; Tung, Roderick; Sadananda, Ramana; Goldberger, Jeffrey J.; Horvath, George; Parker, Michele; Kadish, Alan H.

doi:10.1016/s0002-9149(98)00523-2

Cited by 67 publications

(39 citation statements)

References 17 publications

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“…Additionally, we found no differences in APD 90 between premenopausal and postmenopausal women ( Figure 1C), suggesting that the role of gonadal backgrounds is limited, as reported previously. [32][33][34] From the present study, however, we cannot draw firm conclusions regarding age and menopausal effects on APD differences due to the small num- ber of hearts, particularly those of subjects in their teens and twenties. The cardiac AP results from a complex interplay of several time-and voltage-dependent ion currents.…”

Section: Discussioncontrasting

confidence: 65%

Gender Disparities in Cardiac Cellular Electrophysiology and Arrhythmia Susceptibility in Human Failing Ventricular Myocytes

et al. 2005

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SUMMARYGender disparities in ECG variables and susceptibility to arrhythmia exist. The basis of these sex-related distinctions in cardiac electrophysiology has been extensively studied in various species, but is virtually unexplored in humans. The aim of this study was to clarify the cellular basis of electrophysiological gender disparities in human cardiac myocytes.Human midmyocardial left ventricular myocytes were isolated from explanted hearts of male and female patients in end-stage heart failure at the time of cardiac transplantation. The action potentials, sarcolemmal ion currents, and susceptibility to the generation of early afterdepolarizations were studied using whole-cell patch-clamp methodology. The functional effects of gender disparities in sarcolemmal ion currents were assessed by computer simulations using the Priebe-Beuckelmann or the ten Tusscher-Noble-Noble-Panfilov human ventricular cell models.Female myocytes had significantly longer action potentials and greater susceptibility to early afterdepolarizations than male myocytes. All other action potential parameters (resting membrane potential, amplitude, plateau level, upstroke velocity, maximal velocity of phase-1 and phase-3 repolarization) had similar values for both genders. In female myocytes, the transient outward potassium current (I to1 ) tended to be smaller, while the Ltype calcium current (I Ca,L ) and quasi-steady state current (I QSS ) tended to be larger. Computer simulations showed that these subtle differences in sarcolemmal ion currents may conspire to cause the observed gender disparities in action potential properties.Female failing myocytes have longer action potentials and a greater susceptibility to early afterdepolarizations than male failing myocytes. These gender disparities may be due to slightly larger depolarizing I Ca,L in conjunction with slightly smaller repolarizing I QSS and I to1 in female myocytes. (Int Heart J 2005; 46: 1105-1118

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Section: Discussioncontrasting

confidence: 65%

Gender Disparities in Cardiac Cellular Electrophysiology and Arrhythmia Susceptibility in Human Failing Ventricular Myocytes

et al. 2005

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“…2). Although conflicting results exist regarding the effects of endogenous estrogen on the cardiac repolarization process, several clinical studies have reported that exogenous estrogen therapy but not progesterone/estrogen therapy lengthens the QT intervals (Kadish et al, 2004;Carnethon et al, 2003;Larsen et al, 1998). However, the transcriptional targets of estrogen have not been clarified, and no studies have examined the delivery route of exogenous estrogens.…”

Section: Discussionmentioning

confidence: 99%

Aromatase knockout mice reveal an impact of estrogen on drug-induced alternation of murine electrocardiography parameters

et al. 2015

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-Our in vitro characterization showed that physiological concentrations of estrogen partially suppressed the I Kr channel current in guinea pig ventricular myocytes and the human ether-a-gogo-related gene (hERG) channel currents in CHO-K1 cells regardless of estrogen receptor signaling and revealed that the partially suppressed hERG currents enhanced the sensitivity to the hERG blocker E-4031. To obtain in vivo proof-of-concept data to support the effects of estrogen on cardiac electrophysiology, we here employed an aromatase knockout mouse as an in vivo estrogen-null model and compared the acute effects of E-4031 on cardiac electrophysiological parameters with those in wild-type mice (C57/ BL6J) by recording surface electrocardiogram (ECG). The ablation of circulating estrogens blunted the effects of E-4031 on heart rate and QT interval in mice under a denervation condition. Our result provides in vivo proof of principle and demonstrates that endogenous estrogens increase the sensitivity of E-4031 to cardiac electrophysiology.

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“…When these studies are compared, the question is whether estrogen predisposes to ventricular rhythm disorders via a torsades de pointes mechanism due to the longer QT interval in women, particularly in those treated with antiarrhythmic drugs, prolonging the QT interval or protects against ventricular arrhythmia by decreasing QTd. Larsen, et al 14) have reported that no significant effect of HRT (estrogen or estrogen plus progesterone) was seen on the QT interval or QTc interval, and the estrogen effect in the dosages and forms given clinically should not increase a woman's risk for torsades de pointes. On the other hand, in a study conducted by Haseroth, et al 17) women receiving HRT for 3 months were separated into two groups-those given only estrogen and others given estrogen plus progesterone-and they were compared with the control group.…”

Section: Discussionmentioning

confidence: 99%

“…13) Therefore, it can be considered that hormone replacement therapy (HRT) leads to early afterdepolarizations and consequently leads to ventricular tachycardia by prolonging the QT interval. 14) In the studies conducted thus for, the effects of short-term HRT on the QTd and corrected QT dispersion (QTcd) on the ECG have been investigated. However, data regarding the effects of long term HRT on QT parameters during resting and exercise ECG are insufficient.…”

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confidence: 99%

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

et al. 2002

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SUMMARYIt is known that the QT interval is longer in women than men. Estrogen is reported to account for the QT interval prolongation in several studies conducted with hormone replacement therapy (HRT) in postmenopausal women. Along with this, there are conflicting data as regards the effects of HRT on QT interval and dispersion. Moreover, there is no evidence about the effect of HRT on exercise QT parameters.We compared QT parameters obtained from surface electrocardiograms during resting and peak exercise before and after 6 months of HRT consisting of estrogen plus progesterone in healthy postmenopausal women. Twenty-four healthy postmenopausal women were given 0.625 mg/day conjugated estrogens and 2.5 mg/day medroxyprogesterone acetate for 6 months. Exercise stress testing using the Bruce protocol was performed before and after HRT. QT maximum, minimum, dispersion and corrected QT maximum, minimum and dispersion were calculated during resting and peak exercise.HRT resulted in a significant increase in estradiol plasma levels from 24±10 pg/mL to 117±66 pg/mL (P<0.001). There was no significant difference in resting QT parameters after HRT, whereas QT dispersion and corrected QT dispersion were significantly increased during peak exercise (20±7 versus 25±10 ms; P<0.05, 33±12 versus 41±16 ms; P<0.05, respectively). Nonetheless, the other exercise QT parameters were unchanged.The resting QT parameters are not affected by long term HRT consisting of estrogen plus progesterone, which leads to an increase in QT dispersion and corrected QT dispersion during peak exercise. (Jpn Heart J 2002; 43: 1-7)

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Effects of hormone replacement therapy on QT interval

Cited by 67 publications

References 17 publications

Gender Disparities in Cardiac Cellular Electrophysiology and Arrhythmia Susceptibility in Human Failing Ventricular Myocytes

Gender Disparities in Cardiac Cellular Electrophysiology and Arrhythmia Susceptibility in Human Failing Ventricular Myocytes

Aromatase knockout mice reveal an impact of estrogen on drug-induced alternation of murine electrocardiography parameters

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

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