Aim: To determine the effect of a 12-month intent-to-treat testosterone (T) replacement therapy (TRT) trial on QTa interval variability (QTaVI) in hypogonadal (HG) men with spinal cord injury (SCI). Method: A prospective, controlled 12-month TRT trial was completed in 22 healthy, chronic, nonambulatory men with SCI. Based on serum T concentration, subjects were designated as HG (≤11.3 nmol/l) or eugonadal (EG ≥11.4 nmol/l). Digital 3-lead electrocardiograms were performed. Heart rate (RR), heart rate variability [including total power (TPRR), low frequency (LFRR) and high frequency (HFRR)], QTa, QTe, and RT intervals, QTC (Bazett formula), QTVN, and QTaVI were calculated and evaluated at baseline and at 12 months. Lipoprotein profiles (triglycerides, total cholesterol, low-density and high-density lipoproteins) were obtained at the respective time points. Results: Based on serum T concentration, 13 subjects were designated as HG and 11 as EG. During the trial, there were no group differences for RR, QTa, QTe or RT intervals, QTC, TPRR, HFRR, or lipoproteins. The HG group was older (p < 0.05) and their LFRR was lower (p < 0.05) at baseline. At baseline, QTaVI was significantly greater in the HG group compared to the EG group [-0.17 (0.92) vs. -1.07 (0.90); p < 0.05]. After TRT, this group difference was no longer present [-0.44 (0.87) vs. -0.65 (0.85)] and the change in the HG group was significant (p < 0.05). Conclusion: Hypogonadism in men with SCI was associated with elevated QTaVI at baseline. After 12 months of physiological TRT, the QTaVI improved in association with raising T into the normal range. These findings occurred independently of the prolongation of the QT interval.

Chahla EJ, Hayek ME, Morley JE: Testosterone replacement therapy and cardiovascular risk factors modification. Aging Male 2011;14:83-90.
Channer KS: Endogenous testosterone levels and cardiovascular disease in healthy men. Heart 2011;97:867-869.
Khaw KT, Dowsett M, Folkerd E, Bingham S, Wareham N, Luben R, et al: Endogenous testosterone and mortality due to all causes, cardiovascular disease, and cancer in men: European prospective investigation into cancer in Norfolk (EPIC-Norfolk) Prospective Population Study. Circulation 2007;116:2694-2701.
Charbit B, Christin-Maitre S, Demolis JL, Soustre E, Young J, Funck-Brentano C: Effects of testosterone on ventricular repolarization in hypogonadic men. Am J Cardiol 2009;103:887-890.
Pecori Giraldi F, Toja PM, Filippini B, Michailidis J, Scacchi M, Stramba Badiale M, et al: Increased prevalence of prolonged QT interval in males with primary or secondary hypogonadism: a pilot study. Int J Androl 2010;33:e132-e138.
Kirilmaz A, Bolu E, Kilicaslan F, Erinc K, Uzun M, Isik E, et al: Comparison of electrocardiographic repolarization patterns between hypogonad males and normal subjects. Ann Noninvas Electrocardiol 2003;8:284-288.
Couderc JP: Measurement and regulation of cardiac ventricular repolarization: from the QT interval to repolarization morphology. Philos Transact A Math Phys Eng Sci 2009;367:1283-1299.
Extramiana F, Tavernier R, Maison-Blanche P, Neyroud N, Jordaens L, Leenhardt A, et al: Ventricular repolarization and Holter monitoring. Effect of sympathetic blockage on the QT/RR ratio. Arch Mal Coeur Vaiss 2000;93:1277-1283.
Schwartz PJ: The autonomic nervous system and sudden death. Eur Heart J 1998;19(suppl F):F72-F80.
Atiga WL, Calkins H, Lawrence JH, Tomaselli GF, Smith JM, Berger RD: Beat-to-beat repolarization lability identifies patients at risk for sudden cardiac death. J Cardiovasc Electrophysiol 1998;9:899-908.
Berger RD, Kasper EK, Baughman KL, Marban E, Calkins H, Tomaselli GF: Beat-to-beat QT interval variability: novel evidence for repolarization lability in ischemic and nonischemic dilated cardiomyopathy. Circulation1997;96:1557-1565.
Mine T, Shimizu H, Hiromoto K, Furukawa Y, Kanemori T, Nakamura H, et al: Beat-to-beat QT interval variability is primarily affected by the autonomic nervous system. Ann Noninvasive Electrocardiol 2008;13:228-233.
Piccirillo G, Cacciafesta M, Lionetti M, Nocco M, Di Giuseppe V, Moise A, et al: Influence of age, the autonomic nervous system and anxiety on QT-interval variability. Clin Sci (Lond) 2001;101:429-438.
La Fountaine MF, Wecht JM, Rosado-Rivera D, Cirnigliaro CM, Spungen AM, Bauman WA: The QT variability index and cardiac autonomic modulation: perspectives from apparently healthy men with spinal cord injury. Cardiology 2010;117:253-259.
Safarinejad MR: Level of injury and hormone profiles in spinal cord-injured men. Urology 2001;58:671-676.
Kostovski E, Iversen PO, Birkeland K, Torjesen PA, Hjeltnes N: Decreased levels of testosterone and gonadotrophins in men with long-standing tetraplegia. Spinal Cord 2008;46:559-564.
La Fountaine MF, Wecht JM, Cirnigliaro CM, Kirshblum SC, Spungen AM, Bauman WA: QT/RR coherence is associated with testosterone levels in men with chronic spinal cord injury. Neuroendocrinology 2011;93:174-180.
Alexander MS, Biering-Sorensen F, Bodner D, Brackett NL, Cardenas D, Charlifue S, et al: International standards to document remaining autonomic function after spinal cord injury. Spinal Cord 2009;47:36-43.
Bauman WA, Cirnigliaro CM, La Fountaine MF, Jensen AM, Wecht JM, Kirshblum SC, et al: A small-scale clinical trial to determine the safety and efficacy of testosterone replacement therapy in hypogonadal men with spinal cord injury. Horm Metab Res 2011;43:574-579.
Harman SM, Metter EJ, Tobin JD, Pearson J, Blackman MR. Longitudinal effects of aging on serum total and free testosterone levels in healthy men. Baltimore Longitudinal Study of Aging. J Clin Endocrinol Metab 2001;86:724-731.
Bazett HC: An analysis of time relations of electrocardiogram. Heart 1920;7:353-370.
Akselrod S, Gordon D, Ubel FA, Shannon DC, Berger AC, Cohen RJ: Power spectrum analysis of heart rate fluctuation: a quantitative probe of beat-to-beat cardiovascular control. Science 1981;213:220-222.
Pagani M, Lombardi F, Guzzetti S, Rimoldi O, Furlan R, Pizzinelli P, et al: Power spectral analysis of heart rate and arterial pressure variabilities as a marker of sympatho-vagal interaction in man and conscious dog. Circ Res 1986;59:178-193.
La Fountaine MF, Wecht JM, Spungen AM, Bauman WA: Intra-inter visit reproducibility of short-term linear and nonlinear measurement of heart rate variability in tetraplegia and neurologically intact controls. Physiol Meas 2010;31:363-374.
Ermis N, Deniz F, Kepez A, Kara B, Azal O, Kutlu M: Heart rate variability of young men with idiopathic hypogonadotropic hypogonadism. Auton Neurosci 2010;152:84-87.
Fulop L, Banyasz T, Szabo G, Toth IB, Biro T, Lorincz I, et al: Effects of sex hormones on ECG parameters and expression of cardiac ion channels in dogs. Acta Physiol (Oxf) 2006;188:163-171.
Kaab S, Dixon J, Duc J, Ashen D, Nabauer M, Beuckelmann DJ, et al: Molecular basis of transient outward potassium current downregulation in human heart failure: a decrease in Kv4.3 mRNA correlates with a reduction in current density. Circulation1998;98:1383-1393.
Zicha S, Xiao L, Stafford S, Cha TJ, Han W, Varro A, et al: Transmural expression of transient outward potassium current subunits in normal and failing canine and human hearts. J Physiol 2004;561:735-748.
El-Mas MM, Afify EA, Mohy El-Din MM, Omar AG, Sharabi FM: Testosterone facilitates the baroreceptor control of reflex bradycardia: role of cardiac sympathetic and parasympathetic components. J Cardiovasc Pharmacol 2001;38:754-763.
Garshick E, Kelley A, Cohen SA, Garrison A, Tun CG, Gagnon D, et al: A prospective assessment of mortality in chronic spinal cord injury. Spinal Cord 2005;43:408-416.
Wahman K, Nash MS, Lewis JE, Seiger A, Levi R: Increased cardiovascular disease risk in Swedish persons with paraplegia: The Stockholm spinal cord injury study. J Rehabil Med 2010;42:489-492.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.