Vasomotor hot flashes and cardiac repolarization: A randomized placebo-controlled trial of postmenopausal hormone therapy

Objective: The aim of the study was to compare the effects of different hormone therapies on cardiac repolarization in recently postmenopausal women with and without hot flashes. Methods: We recruited 150 healthy women: 72 with and 78 without hot flashes. They were randomized and treated for 6 months with transdermal estradiol (1 mg/day), oral estradiol (OE) alone (2 mg/day) or combined with medroxyprogesterone acetate (MPA; 5 mg/day), or placebo. Cardiac repolarization was assessed by measuring QT intervals, rate-dependence of QT-end interval, and T waves from 24-hour electrocardiographic recording before and during hormone therapy, comprising a total of over 20 million QT-interval measurements. Results: Hot flashes were accompanied with shortened median T-peak - T-end interval (at RR interval of 700, 800, and 900 ms; P = 0.040, 0.020, and 0.032; η² = 0.35, 0.39, and 0.37; respectively) during the use of OE but not transdermal estradiol. In contrast, the addition of MPA to OE lengthened the maximal QT-end (at RR interval of 500 ms, P = 0.016, η² = 0.27) and the maximal T-peak - T-end interval (at RR interval of 500 and 600 ms; P = 0.016 and 0.032; η² = 0.25 and 0.22, respectively). These effects were not seen in women without hot flashes. Conclusions: Hot flashes predict beneficial shortening in cardiac repolarization during OE, but not if MPA is combined with OE. These data may provide one explanation for MPA-related cardiac hazards in epidemiological studies.