Beyond Estrogen: Aging and Declining Cardiac Autonomic Modulation Are Linked to Longer QTc After Menopause

Women are more susceptible than men to QT prolongation and ventricular arrhythmias, yet how aging and cardiac autonomic control jointly affect the QTc interval in women, independent of fluctuating sex hormones, remains unclear. We hypothesized that QTc is longer in postmenopausal than in young women, and that this difference reflects aging and age-related changes in cardiac autonomic control rather than sex-hormone levels. We studied 64 healthy menstruating women (median age 29.5 years) in the early follicular phase, when estrogen and progesterone are low, and 35 healthy postmenopausal women (median age 67 years). This design minimized acute hormonal differences. QT intervals and heart rate variability (HRV; power spectral analysis) were measured. QT, QTc and JTc, the latter reflecting ventricular repolarization, were longer in postmenopausal women (P < 0.001; η² ≥ 0.14). Postmenopausal women also had lower ln-transformed total power (P < 0.001), LF power (P = 0.006; η² = 0.09) and HF power (P < 0.001; η² = 0.17), and a higher LF/HF ratio (P < 0.001; η² = 0.16). In postmenopausal women, QTc correlated modestly and negatively with total power and LF power (both P = 0.02), but not in young women. Because acute hormonal differences were minimized, the longer QTc after menopause is more consistent with aging and reduced cardiac autonomic modulation than with the prevailing sex-hormone milieu. These findings suggest that age-related autonomic decline, together with a higher LF/HF ratio, may contribute to QT vulnerability in postmenopausal women, with implications for arrhythmic risk assessment and QT-prolonging drug prescription.