• Jie Zhao, Chaoqiang Jiang, Tai Hing Lam, Bin Liu, Kar Keung Cheng, Lin Xu, Mei Jing Long, Weisen Zhang, Gabriel M Leung, and C Mary Schooling.
• School of Public Health, The University of Hong Kong, Hong Kong SAR, China, Guangzhou Number 12 Hospital, Guangzhou, China, Department of Public Health and Epidemiology, University of Birmingham, Birmingham, UK and School of Urban Public Health, Hunter College, CUNY School of Public Health, New York, NY, USA.
• Int J Epidemiol. 2015 Apr 1; 44 (2): 613-20.

BackgroundQT interval prolongation, a predictor of cardiac arrhythmias, and elevated heart rate are associated with higher risk of cardiovascular mortality. Observationally testosterone is associated with shorter corrected QT interval and slower heart rate; however, the evidence is open to residual confounding and reverse causality. We examined the association of testosterone with electrocardiogram (ECG) parameters using a separate-sample instrumental variable (SSIV) estimator.MethodsTo minimize reverse causality, a genetic score predicting testosterone was developed in 289 young Chinese men from Hong Kong, based on a parsimonious set of single nuclear polymorphisms (rs10046, rs1008805 and rs1256031). Linear regression was used to examine the association of genetically predicted testosterone with QT interval, corrected QT interval [using the Framingham formula (QTf) and Bazett formula (QTb)] and heart rate in 4212 older (50+ years) Chinese men from the Guangzhou Biobank Cohort Study.ResultsPredicted testosterone was not associated with QT interval [-0.08 ms per nmol/l testosterone, 95% confidence interval (CI) -0.81 to 0.65], QTf interval (0.40 ms per nmol/l testosterone, 95% CI -0.12 to 0.93) or heart rate (0.26 beats per minute per nmol/l testosterone, 95% CI -0.04 to 0.56), but was associated with longer QTb interval (0.66 ms per nmol/l testosterone, 95% CI 0.02 to 1.31).ConclusionsOur findings do not corroborate observed protective associations of testosterone with QT interval or heart rate among men, but potentially suggest effects in the other direction. Replication in a larger sample is required.© The Author 2014; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.

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