Sex- and Menopause-Specific ECG Repolarization Patterns

Angela Hernandez Mendoza1, Josseline Nicole Madrid1, Neurys Gomez2, Carlos Sánchez3, Patricia Munroe4, Alejandro Sanz5, Ana Mincholé1, Julia Ramírez1
1University of Zaragoza, 2Universidad de Zaragoza, 3Centro Universitario de la Defensa de Zaragoza, 4QMUL, 5Endocrinology service, Miguel Servet University Hospital


Abstract

Sex and menopause influence ventricular repolarization and arrhythmia risk through hormonal effects that may be detectable on the electrocardiogram (ECG). Women have longer QT intervals and narrower QRS-T angles than men, with ECG-based sex misclassification associated with worse outcomes in females. While female hormones are cardioprotective, their decline after menopause may alter ECG patterns. This study aims to identify sex and menopause-related ECG markers of ventricular repolarization and explore their underlying factors. We analyzed ECG markers of ventricular repolarization (the corrected QT, QTc, and T-peak-end, Tpec, intervals and the mean spatial QRS−T angle) in 55,730 healthy individuals from the UK Biobank stratified by sex, and females further subdivided into premenopausal (F-NoMP) and postmenopausal (F-MP) groups. ECG indices were computed per lead and summarized using principal component analysis. Group comparisons used one-tailed Mann–Whitney tests. Significant differences were examined with multiple linear regression to identify key demographic, clinical and cardiac structural and functional contributors. Comparison between sex-specific groups, males showed lower QTc and higher Tpec and QRS−Ta values than females, as well as higher R and T-wave amplitudes in ECG waveforms. Height, body mass index (BMI) and alcohol consumption contributed most in males, whereas menopause, diastolic blood pressure and pulse rate in females. Between F-NoMP and F-MP groups, only Tpec and QRS−Ta differed with F-MP women showing higher values and ECG waveform amplitudes. These differences were driven by left ventricle (LV) wall thickness and LV ejection fraction in both groups and specifically in F-MP, by age, BMI and LV mass. Our results suggest that both sex and menopause are reflected in ECG markers of ventricular repolarization, with F-MP showing subtle changes in morphology toward a pattern analogous to men respect to F-NoMP. These findings suggest the need for further research on hormonal influences in ECG characteristics and arrhythmogenic risk stratification.