Long term effects of hormone replacement therapy on heart rate variability, QT interval, QT dispersion and frequencies of arrhytmia Mustafa Go ¨kc ¸e a, * , Burhan Karahan a , Remzi Yilmaz a , Cihan O ¨ rem a , Cevdet Erdo ¨l a ,S ßafak O ¨ zdemir b a Department of Cardiology, Karadeniz Technical University, Trabzon 61080, Turkey b Department of Obstetrics/Gynecology, Karadeniz Technical University, Trabzon, Turkey Received 31 July 2002; received in revised form 7 January 2003; accepted 11 March 2003 Abstract Background: The aim of the study was to investigate the effects of a long term (1 year) hormone replacement therapy (HRT) on QT interval, QT dispersion (QTd) frequencies of arrhythmia and heart rate variability (HRV) parameters. Methods: Forty-six healthy postmenopausal women (mean age; 55.34 F 4.21) as a hormone replacement therapy group and 25 healthy premenopausal women (mean age; 35.36 F 6.06) as a control group were prospectively enrolled to the study. Hormone replacement therapy group was divided into two groups; estrogen replacement therapy (ERT) group (n = 23) and progestin– estrogen replacement therapy (PERT) group (n = 23). Standard 12 lead electrocardiograms and 24-h ambulatory Holter recording were obtained to evaluate the effects of one year of ERT and PERT on QT intervals, QTd, frequencies of arrhytmias and HRV parameters. Results: Long term use of ERT increases QT interval, QTd, in the frequencies of arrhytmia and HRV indexes of parasympathetic activity; however, the increase in frequencies of arrhythmia was not statistically significant ( p >0.05). Long term use of PERT did not effected QT interval, QTd, frequencies of ventricular arrhythmia and HRV parameters ( p>0.05).Frequency of supraventricular tachycardia increased in post-treatment PERT group was compared with pre-treatment PERT group. Conclusion: These findings supported the hypothesis that estrogen may directly modulate ventricular repolarization. But progestin do not effect the ventricular repolarization. However, these findings must be supported with a large-scale study. D 2003 Elsevier Ireland Ltd. All rights reserved. Keywords: Hormone replacement therapy; QT dispersion and heart rate variability Some experimental and clinical studies demonstrated that hormone replacement therapy (HRT) reduces coronary ar- tery disease risk and the rates of cardiovascular and total mortality in postmenopausal women [1,2]. The beneficial effects of HRT have been attributed to the favorable effects on plasma lipids, hemostatic and vascular factors [3]. But some studies indicated that HRT did not reduce the overall rate of coronary heart disease (CHD) events in postmeno- pausal women with established coronary disease. However, the effects of HRT on myocardial repolarization and auto- nomic tone cannot be excluded [4,5]. QT interval dispersion (QTd) is a non-invasive method of measuring regional inhomogenities in ventricular recovery times [6,7]. High levels of interlead dispersion have been correlated with an increased incidence of ventricular arrhyt- mias [8,9]. QTd has been demonstrated to increase during myocardial ischaemia [10], and to decrease reversal of the ischemic state following thrombolytics [11] or angioplasty [12] QTd has also been demonstrated to decrease in men- opausal patients with syndrome X who received estrogen. In normal adult population, QT and corrected QT (QTc) intervals are longer in women than in men. In addition, women are more likely to develop torsades de pointes when they receive QT lengthening drugs such as antiarrythmics and probucol when compared to men. These suggest that cardiac repolarization has a slower rate in women and female sex may be more prone to QT prolongation induced by various conditions inherited long QT, bradycardia and QT lengthening drugs [13]. In this context of increased arrhytmic risk in females, it is of interest that estrogens and tamoxifen, the classical estrogen receptor antagonist have been shown to modulate the electrophysiological properties of myocytes [14–16]. However, estrogen replacement ther- 0167-5273/$ - see front matter D 2003 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ijcard.2003.03.030 * Corresponding author. Tel.: +90 4623 775594; fax: +90 4623 250518. E-mail address: mustgokce@yahoo.com (M. Go ¨kc ¸e). www.elsevier.com/locate/ijcard International Journal of Cardiology 99 (2005) 373 – 379