Sex Hormones and Repolarization Dynamics During the Menstrual Cycle in Women Treated With QT ‐Prolonging Drugs

BACKGROUND: Women with congenital and acquired long QT syndrome (LQTS) have increased risk of adverse cardiac events after adolescence, mainly due to sex hormones modulating the KCNH2 cardiac potassium channel. We hypothesized that sex hormones may influence ventricular tachyarrhythmia risk during the menstrual cycle in women treated with QT-prolonging drugs. OBJECTIVE: To evaluate the association between repolarization dynamics and sex hormone levels during the menstrual cycle in women treated with QT-prolonging drugs. METHODS: We prospectively enrolled 41 women treated with dofetilide or sotalol (N = 20) and healthy controls (N = 21). Participants underwent three 7-day ECG recordings during their menstrual cycles, with concurrent saliva hormone measurements. Primary ECG outcomes were QT-Apex (early repolarization) and QT interval (total repolarization time), adjusted for heart rate. RESULTS: The mean age was 51 ± 11 years in the treatment group and 42 ± 12 years in controls. In women treated with QT-prolonging drugs, linear mixed-effects models (adjusted for RR interval) showed inverse correlations of QT-Apex with progesterone-to-estradiol ratio (p = 0.018) and testosterone (p = 0.026), and a direct correlation with estradiol (p = 0.004). QT interval inversely correlated with progesterone-to-estradiol ratio (p = 0.012). No significant correlations were observed in controls. CONCLUSIONS: Sex hormones are significantly associated with ventricular repolarization dynamics during the menstrual cycle in women treated with QT-prolonging drugs, suggesting a mechanism for sex-specific arrhythmia susceptibility.