What question did this study set out to answer?

To assess how sex hormones affect repolarization dynamics in women undergoing treatment with QT-prolonging drugs.

January 24, 2026Annals of Noninvasive Electrocardiology1 citationsOpen Access

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

ASAneliya SanUniversity of Rochester Medical Center AYArwa YounisElectrophysiology AYArwa YounisCleveland Clinic

Key Result

In women treated with QT-prolonging drugs, higher estradiol levels are directly correlated with QT-Apex, while the progesterone-to-estradiol ratio is inversely correlated with QT interval.

Key Points

To assess how sex hormones affect repolarization dynamics in women undergoing treatment with QT-prolonging drugs.
Enrolled 41 women treated with dofetilide or sotalol and 21 healthy controls.
Conducted three 7-day ECG recordings during participants' menstrual cycles.
Measured saliva hormone levels alongside ECG data.
QT-Apex showed an inverse correlation with the progesterone-to-estradiol ratio and testosterone.
QT interval inversely correlated with the progesterone-to-estradiol ratio.
No significant correlations were found in the control group.

Structured PICO

Does sex hormone variation during the menstrual cycle influence ventricular repolarization dynamics in women treated with QT-prolonging drugs?

Population

41 women (N=20 treated with dofetilide or sotalol, N=21 healthy controls). Mean age 51 ± 11 years in the treatment group and 42 ± 12 years in controls. Key inclusion: reproductive age (18-50 years) with regular menstrual cycle, treatment with dofetilide or sotalol for >2 months, presence of sinus rhythm.

Intervention

Dofetilide or sotalol treatment for >2 months, monitored with three 7-day ECG recordings and concurrent saliva hormone measurements during the menstrual cycle.

Comparator

Healthy control women undergoing the same ECG and hormone monitoring.

Outcome

QT-Apex (early repolarization) and QT interval (total repolarization time), adjusted for heart rate, measured via three 7-day ECG recordings during the menstrual cycle.surrogate

Sex hormone fluctuations during the menstrual cycle significantly alter ventricular repolarization dynamics in women taking dofetilide or sotalol, suggesting a mechanism for their increased susceptibility to drug-induced arrhythmias.

Limitations

Unknown to what extent these findings apply to other QT prolonging drugs
Small treatment arm of 20 patients may have limited ability to accurately quantify the degree to which sex hormones affect repolarization
Mean age of patients enrolled in the treatment arm tended to be older, making it unclear to what degree age-related coexistent factors contributed

Abstract

ABSTRACT 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.

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