Vasomotor hot flashes and heart rate variability: a placebo-controlled trial of postmenopausal hormone therapy

Objective: The aim of the study was to compare the responses of heart rate variability (HRV) with hormone therapy in recently postmenopausal women with and without vasomotor hot flashes. Methods: Seventy-two women with and 78 women without hot flashes were randomized to receive transdermal estradiol gel (1 g/day), oral estradiol alone (2 mg/day), oral estradiol combined with medroxyprogesterone acetate (MPA; 5 mg/day), or placebo for 6 months. Time-and frequency-domain measures of HRV were assessed using 24-hour electrocardiographic recordings at baseline and after hormone therapy. Results: At baseline, the cardiac variables were similar in women with and without hot flashes. In women with hot flashes, the mean 24-hour heart rate and nighttime heart rate showed a tendency toward reduction in estradiol-only users compared with those taking placebo and those taking estradiol combined with MPA. In women with hot flashes, oral estradiol versus transdermal estradiol reduced nighttime HRV in the time domain (triangular index, -27 +/- 36 vs +8 +/- 36, P = 0.042). In women without hot flashes, the use of oral estradiol with MPA reduced time-domain HRV (SD of all normal-to-normal intervals; -11 +/- 13 ms, P = 0.048, and square root of the mean of the sum of the squares of differences between adjacent normal-to-normal intervals; -6 +/- 8 ms, P = 0.036). The women with hot flashes had more supraventricular ectopic beats when using oral estradiol with MPA than when using oral estradiol only (71 +/- 128 vs 12 +/- 11, P = 0.018). Conclusions: Oral estrogen, especially when combined with MPA, may have adverse effects on HRV in women with and without hot flashes, whereas transdermal estradiol showed no such effects. Furthermore, women with hot flashes receiving oral estrogen combined with MPA are possibly more prone to cardiac arrhythmias than are women using estrogen only.