Acute Effects of Sex Steroid Hormones on Susceptibility to Cardiac Arrhythmias: A Simulation Study
Open accessAbstract
Acute effects of sex steroid hormones likely contribute to the observation that post-pubescent males have shorter QT intervals than females. However, the specific role for hormones in modulating cardiac electrophysiological parameters and arrhythmia vulnerability is unclear. Here we use a computational modeling approach to incorporate experimentally measured effects of physiological concentrations of testosterone, estrogen and progesterone on cardiac ion channel targets. We then study the hormone effects on ventricular cell and tissue dynamics comprised of Faber-Rudy computational models. The "female" model predicts changes in action potential duration (APD) at different stages of the menstrual cycle that are consistent with clinically observed QT interval fluctuations. The "male" model predicts shortening of APD and QT interval at physiological testosterone concentrations. The model suggests increased susceptibility to drug-induced arrhythmia when estradiol levels are high, while testosterone and progesterone are apparently protective. Simulations predict the effects of sex steroid hormones on clinically observed QT intervals and reveal mechanisms of estrogen-mediated susceptibility to prolongation of QT interval. The simulations also indicate that acute effects of estrogen are not alone sufficient to cause arrhythmia triggers and explain the increased risk of females to Torsades de Pointes. Our results suggest that acute effects of sex steroid hormones on cardiac ion channels are sufficient to account for some aspects of gender specific susceptibility to long-QT linked arrhythmias.
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All three studies identified through the search suggested that sex is not a significant modifier of dementia in individuals with AF.
“All three studies identified through our search suggested that sex is not a significant modifier of dementia in individuals with AF.88–90”
From Atrial fibrillation in women: epidemiology, pathophysiology, presentation, and prognosis (2016) · cites this paper as [89]
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Molecular and Cellular Basis of Cardiovascular Gender Differences
Mendelsohn, M. E., & Karas, R. H. (2005) · Science · doi:10.1126/science.1112062 · Cited by 1,101 · see citing works
Female Gender as a Risk Factor for Torsades de Pointes Associated With Cardiovascular Drugs
Makkar, R. (1993) · JAMA · doi:10.1001/jama.270.21.2590 · Cited by 972 · see citing works
Drug induced QT prolongation and torsades de pointes
Yap, Y. G., & Camm, A. J. (2003) · Heart · doi:10.1136/heart.89.11.1363 · Cited by 958 · see citing works
Sex differences in the evolution of the electrocardiographic QT interval with age.
Rautaharju, P. M., Sh, Z., Wong, S., Hp, C., Berenson, G. S., Prineas, R., & Davignon, A. (1992) · PubMed · Cited by 635 · see citing works
Locati, E. H., Zaręba, W., Moss, A. J., Schwartz, P. J., Vincent, G. M., Lehmann, M. H., Towbin, J. A., Priori, S. G., Napolitano, C., Robinson, J. L., et al. (1998) · Circulation · doi:10.1161/01.cir.97.22.2237 · Cited by 490 · see citing works
Sex Difference in Risk of Torsade de Pointes With d,l- Sotalol
Lehmann, M. H., Hardy, S. A., Archibald, D., Quart, B. D., & MacNeil, D. J. (1996) · Circulation · doi:10.1161/01.cir.94.10.2535 · Cited by 459 · see citing works
Action Potential and Contractility Changes in [Na+]i Overloaded Cardiac Myocytes: A Simulation Study
Faber, G. M., & Rudy, Y. (2000) · Biophysical Journal · doi:10.1016/s0006-3495(00)76783-x · Cited by 439 · see citing works
Improta-Brears, T., Whorton, A. R., Codazzi, F., York, J. D., Meyer, T., & McDonnell, D. P. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.8.4686 · Cited by 342 · see citing works
Drug-Induced QT Prolongation in Women During the Menstrual Cycle
Rodríguez, I. (2001) · JAMA · doi:10.1001/jama.285.10.1322 · Cited by 315 · see citing works
Therapeutic implications of the gender-specific aspects of cardiovascular disease
Regitz‐Zagrosek, V. (2006) · Nature Reviews Drug Discovery · doi:10.1038/nrd2032 · Cited by 282 · see citing works
Yan, G., Wu, Y., Liu, T., Wang, J., Marinchak, R. A., & Kowey, P. R. (2001) · Circulation · doi:10.1161/01.cir.103.23.2851 · Cited by 269 · see citing works
Nontranscriptional Regulation of Cardiac Repolarization Currents by Testosterone
Bai, C., Kurokawa, J., Tamagawa, M., Nakaya, H., & Furukawa, T. (2005) · Circulation · doi:10.1161/circulationaha.104.523217 · Cited by 254 · see citing works
Self-citationThe influence of menstrual cycle phase on skeletal muscle contractile characteristics in humans
de Jonge, X. J., Boot, C. R. L., Thom, J. M., Ruell, P. A., & Thompson, M. W. (2001) · The Journal of Physiology · doi:10.1111/j.1469-7793.2001.0161m.x · Cited by 246 · see citing works
Gender Difference in the Cycle Length-Dependent QT and Potassium Currents in Rabbits
Liu, X.-K., Katchman, A., Drici, M.-D., Ebert, S. N., Ducic, I., Morad, M., & Woosley, R. L. (1998) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(24)37435-x · Cited by 209 · see citing works
Recent advances in understanding sex differences in cardiac repolarization
James, A. F., Choisy, S. C. M., & Hancox, J. C. (2005) · Progress in Biophysics and Molecular Biology · doi:10.1016/j.pbiomolbio.2005.05.010 · Cited by 205 · see citing works
Sex, hormones, and repolarization
Pham, T. D. (2002) · Cardiovascular Research · doi:10.1016/s0008-6363(01)00429-1 · Cited by 202 · see citing works
Cardiac Actions of Erythromycin
Drici, M., Knollmann, B. C., Wang, W.-X., & Woosley, R. L. (1998) · JAMA · doi:10.1001/jama.280.20.1774 · Cited by 197 · see citing works
Pause induced early afterdepolarizations in the long QT syndrome: a simulation study
Viswanathan, P. (1999) · Cardiovascular Research · doi:10.1016/s0008-6363(99)00035-8 · Cited by 193 · see citing works
Nakamura, H., Kurokawa, J., Bai, C.-X., Asada, K., Xu, J., Oren, R. V., Zhu, Z. I., Clancy, C. E., Isobe, M., & Furukawa, T. (2007) · Circulation · doi:10.1161/circulationaha.107.702407 · Cited by 190 · see citing works
Self-citationBurke, J. H., Ehlert, F. A., Kruse, J. T., Parker, M. A., Goldberger, J. J., & Kadish, A. H. (1997) · The American Journal of Cardiology · doi:10.1016/s0002-9149(96)00707-2 · Cited by 189 · see citing works
Cellular consequences of HERG mutations in the long QT syndrome: precursors to sudden cardiac death
Clancy, C. E. (2001) · Cardiovascular Research · doi:10.1016/s0008-6363(00)00293-5 · Cited by 182 · see citing works
Self-citationInfluence of Menstrual Cycle on QT Interval Dynamics
Nakagawa, M., Ooie, T., Takahashi, N., Taniguchi, Y., Anan, F., Yonemochi, H., & Saikawa, T. (2006) · Pacing and Clinical Electrophysiology · doi:10.1111/j.1540-8159.2006.00407.x · Cited by 174 · see citing works
Liu, X. (2002) · Cardiovascular Research · doi:10.1016/s0008-6363(02)00673-9 · Cited by 150 · see citing works
Kurokawa, J., Tamagawa, M., Harada, N., Honda, S., Bai, C., Nakaya, H., & Furukawa, T. (2008) · The Journal of Physiology · doi:10.1113/jphysiol.2007.150367 · Cited by 148 · see citing works
Self-citationPham, T. V., Sosunov, E. A., Gainullin, R. Z., Danilo, P., & Rosen, M. R. (2001) · Circulation · doi:10.1161/01.cir.103.17.2207 · Cited by 143 · see citing works
Sex differences in ventricular repolarization: from cardiac electrophysiology to Torsades de Pointes
Abi‐Gerges, N., Philp, K. L., Pollard, C. E., Wakefield, I. D., Hammond, T. G., & Valentin, J. (2004) · Fundamental and Clinical Pharmacology · doi:10.1111/j.1472-8206.2004.00230.x · Cited by 135 · see citing works
Virág, L. (2001) · Cardiovascular Research · doi:10.1016/s0008-6363(00)00306-0 · Cited by 135 · see citing works
The female sex hormone oestrogen as a neuroprotectant
Behl, C., & Holsboer, F. (1999) · Trends in Pharmacological Sciences · doi:10.1016/s0165-6147(99)01392-9 · Cited by 133 · see citing works
Age‐related changes in testosterone and the role of replacement therapy in older men
Allan, C. A., & McLachlan, R. I. (2004) · Clinical Endocrinology · doi:10.1111/j.1365-2265.2004.02002.x · Cited by 128 · see citing works
Sims, C., Reisenweber, S. M., Viswanathan, P. C., Choi, B., Walker, W. H., & Salama, G. (2008) · Circulation Research · doi:10.1161/circresaha.108.173740 · Cited by 124 · see citing works
Measurement of steroid sex hormones in serum: a comparison of radioimmunoassay and mass spectrometry
Dorgan, J. F., Fears, T. R., McMahon, R. P., Friedman, L. A., Patterson, B. H., & Greenhut, S. F. (2002) · Steroids · doi:10.1016/s0039-128x(01)00147-7 · Cited by 123 · see citing works
Effects of Gonadal Steroids on Ventricular Repolarization and on the Response to E4031
Hara, M., Danilo, P., & Rosen, M. R. (1998) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(24)37516-0 · Cited by 123 · see citing works
Pham, T. D. (2002) · Cardiovascular Research · doi:10.1016/s0008-6363(01)00449-7 · Cited by 109 · see citing works
Are gender differences in QTc present at birth?
Stramba‐Badiale, M., Spagnolo, D., Bosi, G., & Schwartz, P. J. (1995) · The American Journal of Cardiology · doi:10.1016/s0002-9149(99)80781-4 · Cited by 108 · see citing works
Estrogen and Progestin Use and the QT Interval in Postmenopausal Women
Kadish, A. H., Greenland, P., Limacher, M. C., Frishman, W. H., Daugherty, S. A., & Schwartz, J. B. (2004) · Annals of Noninvasive Electrocardiology · doi:10.1111/j.1542-474x.2004.94580.x · Cited by 105 · see citing works
Guetta, V., Panza, J. A., Waclawiw, M. A., & Cannon, R. O. (1995) · The American Journal of Cardiology · doi:10.1016/s0002-9149(99)80780-2 · Cited by 103 · see citing works
Female preponderance in ibutilide-induced torsade de pointes
Gowda, R. M., Khan, I. A., Punukollu, G., Vasavada, B. C., Sacchi, T. J., & Wilbur, S. L. (2004) · International Journal of Cardiology · doi:10.1016/j.ijcard.2003.04.034 · Cited by 87 · see citing works
Xiao, L., Zhang, L., Han, W., Wang, Z., & Nattel, S. (2006) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.01288.2005 · Cited by 80 · see citing works
Furukawa, T., & Kurokawa, J. (2007) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2007.04.008 · Cited by 79 · see citing works
Self-citationThe Mechanism of Pause‐Induced Torsade de Pointes in Long QT Syndrome
Liu, J., & Laurita, K. R. (2005) · Journal of Cardiovascular Electrophysiology · doi:10.1111/j.1540-8167.2005.40677.x · Cited by 74 · see citing works
Redox- and Calmodulin-dependent S-Nitrosylation of the KCNQ1 Channel
Asada, K., Kurokawa, J., & Furukawa, T. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m807158200 · Cited by 74 · see citing works
Self-citationTestosterone Diminishes the Proarrhythmic Effects of Dofetilide in Normal Female Rabbits
Pham, T. V., Sosunov, E. A., Anyukhovsky, E. P., Danilo, P., & Rosen, M. R. (2002) · Circulation · doi:10.1161/01.cir.0000033596.21845.d8 · Cited by 69 · see citing works
Influence of endogenous oestrogens on QT interval duration
Hulot, J. (2003) · European Heart Journal · doi:10.1016/s0195-668x(03)00436-6 · Cited by 69 · see citing works
Gender-related differences in ventricular myocyte repolarization in the guinea pig
James, A. F., Arberry, L. A., & Hancox, J. C. (2004) · Basic Research in Cardiology · doi:10.1007/s00395-003-0451-6 · Cited by 65 · see citing works
Carnethon, M. R., Anthony, M. S., Cascio, W. E., Folsom, A. R., Rautaharju, P. M., Liao, D., Evans, G. W., & HEISS, G. M. (2003) · Annals of Epidemiology · doi:10.1016/s1047-2797(03)00050-4 · Cited by 64 · see citing works
Verkerk, A. O., Wilders, R., Veldkamp, M. W., de Geringel, W., Kirkels, J. H., & Tan, H. L. (2005) · International Heart Journal · doi:10.1536/ihj.46.1105 · Cited by 60 · see citing works
Effects of progestin–estrogen replacement therapy on QT-dispersion in postmenopausal women
Rossol-Haseroth, K., Seyffart, K., Wehling, M., & Christ, M. (2000) · International Journal of Cardiology · doi:10.1016/s0167-5273(00)00317-x · Cited by 56 · see citing works
Effect of testosterone therapy on QT dispersion in men with heart failure
Malkin, C. J., Morris, P., Pugh, P. J., English, K. M., & Channer, K. S. (2003) · The American Journal of Cardiology · doi:10.1016/j.amjcard.2003.07.044 · Cited by 56 · see citing works
Philp, K. L., Hussain, M., Byrne, N., Diver, M. J., Hart, G., & Coker, S. J. (2006) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0706850 · Cited by 49 · see citing works
Patterson, E. S., Ma, L., Szabo, B., Robinson, C. P., & Thadani, U. (1998) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(24)37257-x · Cited by 48 · see citing works
Specific Regulation of Lipocalin-Type Prostaglandin D Synthase in Mouse Heart by Estrogen Receptor β
Otsuki, M., Gao, H., Dahlman‐Wright, K., Ohlsson, C., Eguchi, N., Urade, Y., & Gustafsson, J.-Α. (2003) · Molecular Endocrinology · doi:10.1210/me.2003-0016 · Cited by 46 · see citing works
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Ko, D., Rahman, F., Schnabel, R. B., Yin, X., Benjamin, E. J., & Christophersen, I. E. (2016) · Nature Reviews Cardiology · doi:10.1038/nrcardio.2016.45 · Cited by 353 · see citing works
Exploiting mathematical models to illuminate electrophysiological variability between individuals
Sarkar, A. X., Christini, D. J., & Sobie, E. A. (2012) · The Journal of Physiology · doi:10.1113/jphysiol.2011.223313 · Cited by 135 · see citing works
Sex-Specific Cardiovascular Risks of Cancer and Its Therapies
Wilcox, N. S., Rotz, S. J., Mullen, M., Song, E. J., Ky Hamilton, B., Moslehi, J., Armenian, S. H., Wu, J. C., Rhee, J.-W., & Ky, B. (2022) · Circulation Research · doi:10.1161/circresaha.121.319901 · Cited by 86 · see citing works
A Computational Pipeline to Predict Cardiotoxicity
Yang, P., DeMarco, K. R., Aghasafari, P., Jeng, M.-T., Dawson, J. R. D., Bekker, S., Noskov, S. Y., Yarov-Yarovoy, V. M., Vorobyov, I. V., & Clancy, C. E. (2020) · Circulation Research · doi:10.1161/circresaha.119.316404 · Cited by 84 · see citing works
Self-citationMechanisms of sex and age differences in ventricular repolarization in humans
Vicente, J., Johannesen, L., Galeotti, L., & Strauss, D. G. (2014) · American Heart Journal · doi:10.1016/j.ahj.2014.07.010 · Cited by 85 · see citing works
A Heart for Diversity: Simulating Variability in Cardiac Arrhythmia Research
Ni, H., Morotti, S., & Grandi, E. (2018) · Frontiers in Physiology · doi:10.3389/fphys.2018.00958 · Cited by 84 · see citing works
Sex hormonal regulation of cardiac ion channels in drug-induced QT syndromes
Kurokawa, J., Kodama, M., Clancy, C. E., & Furukawa, T. (2016) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2016.09.004 · Cited by 78 · see citing works
Self-citationComputational approaches to understand cardiac electrophysiology and arrhythmias
Roberts, B. N., Yang, P., Vaughn‐Behrens, S. B., Moreno, J. D., & Clancy, C. E. (2012) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.01081.2011 · Cited by 75 · see citing works
Self-citationEffect of Female Sex on Cardiac Arrhythmias
Gowd, B. M. P., & Thompson, P. D. (2012) · Cardiology in Review · doi:10.1097/crd.0b013e318259294b · Cited by 75 · see citing works
Cardiac arrhythmia considerations of hormone cancer therapies
Barber, M., Nguyen, L. S., Wassermann, J., Spano, J., Funck‐Brentano, C., & Salem, J. (2019) · Cardiovascular Research · doi:10.1093/cvr/cvz020 · Cited by 70 · see citing works
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Vandersickel, N., Kazbanov, I. V., Nuitermans, A., Weise, L. D., Pandit, R. A., & Panfilov, A. V. (2014) · PLoS ONE · doi:10.1371/journal.pone.0084595 · Cited by 66 · see citing works
Multiscale Modeling in the Clinic: Drug Design and Development
Clancy, C. E., An, G., Cannon, W. R., Liu, Y., May, E. E., Ortoleva, P., Popel, A. S., Sluka, J. P., Su, J., Vicini, P., et al. (2016) · Annals of Biomedical Engineering · doi:10.1007/s10439-016-1563-0 · Cited by 62 · see citing works
Self-citationIseppe, A. F., Ni, H., Zhu, S., Zhang, X., Coppini, R., Yang, P., Srivatsa, U. N., Clancy, C. E., Edwards, A. G., Morotti, S., et al. (2021) · Clinical Pharmacology & Therapeutics · doi:10.1002/cpt.2240 · Cited by 61 · see citing works
Self-citationBett, G. C. L., Zhou, Q., & Rasmusson, R. L. (2011) · Biophysical Journal · doi:10.1016/j.bpj.2011.06.050 · Cited by 55 · see citing works
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Zeitler, E. P., Poole, J. E., Albert, C. M., Al-Khatib, S. M., Ali-Ahmed, F., Birgersdotter-Green, U., Cha, Y.-M., Chung, M. K., Curtis, A. B., Hurwitz, J. L., et al. (2022) · Circulation Research · doi:10.1161/circresaha.121.319893 · Cited by 54 · see citing works
Bloxham, C. J., Foster, S. R., & Thomas, W. G. (2020) · Frontiers in Physiology · doi:10.3389/fphys.2020.00431 · Cited by 53 · see citing works
Yang, P., Perissinotti, L. L., López, F. M., Wang, Y., DeMarco, K. R., Jeng, M.-T., Vorobyov, I. V., Harvey, R. D., Kurokawa, J., Noskov, S. Y., et al. (2017) · The Journal of Physiology · doi:10.1113/jp273142 · Cited by 49 · see citing works
Self-citationde Lange, E., Xie, Y., & Qu, Z. (2012) · Biophysical Journal · doi:10.1016/j.bpj.2012.06.007 · Cited by 47 · see citing works
Madhvani, R. V., Angelini, M., Xie, Y., Pantazis, A., Suriany, S., Borgstrom, N. P., Garfinkel, A., Qu, Z., Weiss, J. N., & Olcese, R. (2015) · The Journal of General Physiology · doi:10.1085/jgp.201411288 · Cited by 47 · see citing works
Non-genomic Action of Sex Steroid Hormones and Cardiac Repolarization
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Self-citationTrayanova, N. A., O’Hara, T., Bayer, J. D., Boyle, P. M., McDowell, K. S., Constantino, J. L., Arevalo, H., Hu, Y., & Vadakkumpadan, F. (2012) · EP Europace · doi:10.1093/europace/eus277 · Cited by 36 · see citing works
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Tian, X., Xu, Y., & Yang, Y. (2019) · Journal of Cardiovascular Translational Research · doi:10.1007/s12265-019-09918-w · Cited by 35 · see citing works
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Ma, J., Wang, N. Y., Jagani, R., & Wang, H. (2023) · Chemosphere · doi:10.1016/j.chemosphere.2023.138562 · Cited by 34 · see citing works
Zimik, S., Vandersickel, N., Nayak, A. R., Panfilov, A. V., & Pandit, R. A. (2015) · PLoS ONE · doi:10.1371/journal.pone.0130632 · Cited by 33 · see citing works
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Computational Cardiology: The Heart of the Matter
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Sex Differences in Electrophysiology and Calcium Handling in Atrial Health and Fibrillation
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Kumagai, K., Imai, S., Toyoda, F., Okumura, N., Isoya, E., Matsuura, H., & Matsusue, Y. (2011) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2011.01802.x · Cited by 26 · see citing works
An Introduction to Computational Modeling of Cardiac Electrophysiology and Arrhythmogenicity
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Sakamoto, K., & Kurokawa, J. (2019) · Journal of Pharmacological Sciences · doi:10.1016/j.jphs.2019.02.009 · Cited by 25 · see citing works
Self-citationPiccirillo, G., Moscucci, F., Pofi, R., D’Alessandro, G., Minnetti, M., Isidori, A. M., Francomano, D., Lenzi, A., Puddu, P. E., Alexandre, J., et al. (2019) · Journal of Endocrinological Investigation · doi:10.1007/s40618-019-01026-5 · Cited by 24 · see citing works
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Walters, T. E., Teh, A. W., Spence, S. J., Morton, J. B., Kistler, P. M., & Kalman, J. M. (2014) · Journal of Cardiovascular Electrophysiology · doi:10.1111/jce.12465 · Cited by 22 · see citing works
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Ma, J., Hong, K., & Wang, H. (2017) · Endocrinology · doi:10.1210/en.2016-1702 · Cited by 20 · see citing works
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Subbamanda, Y., & Bhargava, A. (2022) · Cells · doi:10.3390/cells11233850 · Cited by 19 · see citing works
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Yang, P.-C., & Clancy, C. E. (2011) · Journal of Biomedical Research · doi:10.1016/s1674-8301(11)60010-9 · Cited by 16 · see citing works
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Galli‐Τsinopoulou, A., Chatzidimitriou, A., Kyrgios, I., Rousso, I., Varlamis, G., & Karavanaki, K. (2013) · Journal of Pediatric Endocrinology and Metabolism · doi:10.1515/jpem-2013-0193 · Cited by 15 · see citing works
Antoun, I., Layton, G. R., Abdelrazik, A., Eldesouky, M., Zakkar, M., Somani, R., & Ng, G. A. (2025) · Medicina · doi:10.3390/medicina61040649 · Cited by 14 · see citing works
Li, Y., Sun, X., Zang, L., Zhang, Q., Ji-chun, L., & Zou, S. (2013) · Endocrine · doi:10.1007/s12020-013-9953-7 · Cited by 14 · see citing works
A review of contraceptive methods for women with cardiac disease
Jakes, A. D., Coad, F., & Nelson‐Piercy, C. (2018) · The Obstetrician & Gynaecologist · doi:10.1111/tog.12446 · Cited by 13 · see citing works
Gual‐Capllonch, F., de Ibarra, J. I. S., Bayés‐Genís, A., & Delgado, V. (2022) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2022.877592 · Cited by 12 · see citing works
Computational models for predictive cardiac ion channel pharmacology
Yarov-Yarovoy, V. M., Allen, T. W., & Clancy, C. E. (2014) · Drug Discovery Today Disease Models · doi:10.1016/j.ddmod.2014.04.001 · Cited by 12 · see citing works
Self-citationSynnergren, J., Vukušić, K., Dönnes, P., Jonsson, M., Lindahl, A. H., Dellgren, G., Jeppsson, A., & Asp, J. (2019) · Physiological Genomics · doi:10.1152/physiolgenomics.00036.2019 · Cited by 11 · see citing works
Computational Cardiac Safety Testing
Mirams, G. R. (2023) · Springer eBooks · doi:10.1007/978-3-030-73317-9_137-1 · Cited by 10 · see citing works
Sağlam, H. S., Cakar, M., Köse, O., Kumsar, Ş., Budak, S., Beyaz, S. G., & Adsan, Ö. (2012) · Open Journal of Urology · doi:10.4236/oju.2012.223029 · Cited by 8 · see citing works
Vandersickel, N., Kazbanov, I. V., Defauw, A., Pijnappels, D. A., & Panfilov, A. V. (2015) · Heart Rhythm · doi:10.1016/j.hrthm.2015.01.033 · Cited by 8 · see citing works
Raman, A. P. S., Tomar, J., Jain, P., Kumar, A., Singh, P., & Kumari, K. (2023) · ChemistrySelect · doi:10.1002/slct.202303320 · Cited by 7 · see citing works
Associations of Sex Hormones With Surface Electrocardiogram J Point Amplitude in Healthy Volunteers
McNamara, D. A., Ng, J., Ilkhanoff, L., Schaechter, A., Goldberger, J. J., & Kadish, A. H. (2017) · The American Journal of Cardiology · doi:10.1016/j.amjcard.2017.02.035 · Cited by 7 · see citing works
Mechanistic insights into spontaneous transition from cellular alternans to ventricular fibrillation
You, T., Xie, Y., Luo, C., Zhang, K., & Zhang, H. (2023) · Physiological Reports · doi:10.14814/phy2.15619 · Cited by 7 · see citing works
Yin, Z., Torre, E., Marrot, M., Peters, C. H., Feather, A., Nichols, W. G., Logantha, S. J. R. J., Arshad, A., Martis, S. A., Ozturk, N. T., et al. (2024) · Frontiers in Medicine · doi:10.3389/fmed.2024.1488478 · Cited by 5 · see citing works
Mechanisms of Chemical Atrial Defibrillation by Flecainide and Ibutilide
Yang, P., Belardinelli, L., & Clancy, C. E. (2024) · JACC. Clinical electrophysiology · doi:10.1016/j.jacep.2024.08.009 · Cited by 4 · see citing works
Self-citationFeminizing Adrenal Carcinoma Presenting with Heart Failure and Ventricular Tachycardia
Harnoor, A., West, R. L., & Cook, F. (2012) · Case Reports in Endocrinology · doi:10.1155/2012/760134 · Cited by 3 · see citing works
The impact of testosterone levels on J-wave patterns observed in healthy Turkish males
Hünük, B. (2019) · The European Research Journal · doi:10.18621/eurj.519192 · Cited by 3 · see citing works
Dominguez-Gomez, P., Butakoff, C., Rast, G. F., Darpö, B., Vázquez, M., & Aguado‐Sierra, J. (2025) · The Journal of Precision Medicine Health and Disease · doi:10.1016/j.premed.2025.100011 · Cited by 2 · see citing works
García, A., Kayani, A. M. A., Lemus-Zamora, R. E., Navarro-Martínez, D. A., Garcia, E. T., Salama-Frisbie, R., Flores, J. R. G., Aviles, E., & Patel, B. D. (2026) · Journal of Interventional Cardiac Electrophysiology · doi:10.1007/s10840-026-02237-6 · Cited by 1 · see citing works
When it comes to the heart, age, and sex matter (sometimes)
Weinberg, S. H., & King, D. R. (2023) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00719.2022 · Cited by 1 · see citing works
Computational Cardiac Safety Testing
Mirams, G. R. (2024) · Springer eBooks · doi:10.1007/978-3-031-35529-5_137 · Cited by 1 · see citing works
Shapira‐Daniels, A., King, D. S., Reisner, S. L., Beach, L. B., Eromosele, O. '. B., Ravichandran, S., Helm, R. H., Benjamin, E. J., & Streed, C. G. (2024) · LGBT Health · doi:10.1089/lgbt.2024.0151 · Cited by 1 · see citing works
Csajbók, É., Orosz, A., Hankovszky, P., Rudas, L., & Lengyel, C. (2013) · Endocrine Abstracts · doi:10.1530/endoabs.32.p320
La fibrilación auricular y su comportamiento en la mujer
Velásquez, J. E., Naranjo, S., Gaviria, M. C., & Duque, M. (2018) · Revista Colombiana de Cardiología · doi:10.1016/j.rccar.2017.11.022
Electrophysiological cellular effects of sex hormones
Bébarová, M. (2020) · Elsevier eBooks · doi:10.1016/b978-0-12-817728-0.00017-6
Hormone and autonomic changes of pregnancy and their impact on cardiac electrophysiology
Tracy, C. M., McCaffrey, J. A., & Karim, S. (2020) · Elsevier eBooks · doi:10.1016/b978-0-12-817728-0.00059-0
Ma, J., & Wang, H. (2022) · SSRN Electronic Journal · doi:10.2139/ssrn.4142260
Qi, J., Kang, D.-Y., Yu, J., & Zhang, M. (2022) · Chinese Journal of Integrative Medicine · doi:10.1007/s11655-022-3623-7
Arrhythmias in Pregnancy. Experience of the Multidisciplinary Team
Сіромаха, С. О., Давыдова, Ю. В., Kravchuk, B. B., Vp, Z., Nakonechna, N. B., & Lazoryshynets, V. V. (2022) · Ukrainian journal of cardiovascular surgery · doi:10.30702/ujcvs/22.30(04)/sd063-104110
The impact of testosterone on the QT interval: A Systematic reviewPreprint
Gutiérrez, G., Wamboldt, R., & Baranchuk, A. M. (2024) · doi:10.22541/au.170665176.67022249/v1
Influence of Oestrogen on Atrial Fibrillation Risk: An In-Silico Study
Kulkarni, A., Barrows, R. K., Strocchi, M., Augustin, C. M., Gsell, M. A. F., Vigmond, E. J., Plank, G., Panay, N., & Niederer, S. (2025) · Lecture notes in computer science · doi:10.1007/978-3-031-94559-5_7
Sex-specific virtual population for the prediction and assessment of arrhythmia risk
Sui, F., Yan, D., Meng, X., Duan, C., Zhang, Y., Gao, W., & Song, Z. (2026) · EP Europace · doi:10.1093/europace/euag133
- Authors
- Yang, P.-C., Kurokawa, J., Furukawa, T., & Clancy, C. E.
- Affiliations
- University of California, Davis (US)
- Tokyo Medical and Dental University (JP)
- Corresponding author
- Clancy, Colleen E.
- Venue
- PLoS Computational Biology
- Publisher
- Public Library of Science (PLoS)
- Published
- 2010-01-29
- Volume
- 6
- Issue
- 1
- Pages
- e1000658
- ISSN
- 1553-734X (ISSN-L)
- 1553-7358
- PMC
- PMC2813260
- OpenAlex
- W2140307760
- Cited by
- 75
- References
- 51
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 8 · 2023: 5 · 2022: 8 · 2021: 2 · 2020: 4 · 2019: 6 · 2018: 4 · 2017: 4 · 2016: 3 · 2015: 3 · 2014: 6 · 2013: 5 · 2012: 9
- FWCI
- 3.73
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS Computational Biology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion, cc-by)
- Funders
- Alfred P. Sloan Foundation
- American Heart Association
- Naito Foundation
- National Institutes of Health
- National Heart, Lung, and Blood Institute (NHLBI RO1, R01HL085592)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac electrophysiology and arrhythmias
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Arrhythmias and Treatments
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac pacing and defibrillation studies
- Keywords
- sex hormones, cardiac arrhythmias, QT interval, action potential duration, testosterone, estrogen, estradiol, progesterone, menstrual cycle, torsades de pointes, long QT syndrome, cardiac ion channels, ventricular electrophysiology, drug-induced arrhythmia
- MeSH terms
- Action Potentials, Animals, Anti-Arrhythmia Agents, Arrhythmias, Cardiac, Cells, Cultured, Computer Simulation, Disease Susceptibility, Electrocardiography, Estrogens, Female, Guinea Pigs, Male, Markov Chains, Menstrual Cycle, Piperidines, Progesterone, Pyridines, Gonadal Steroid Hormones, Testosterone, Potassium Channels, Myocytes, Cardiac
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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