Effect of hormone replacement therapy on the electrocardiographic response to exercise

Background. Female gender and hormonal status affect electrocardiographic (ECG) response to exercise. Both are often cited as factors contributing to the decreased diagnostic accuracy of exercise stress tests in women. However, there is a paucity of data. To explore the relationship between hormonal status and exercise-induced ECG changes, we used gated single photon emission computed tomography (SPECT) technetium 99m sestamibi imaging for detection of myocardial ischemia. Methods and Results. ECG response to exercise was analyzed in all female patients who underwent symptom-limited exercise stress testing over a 12-month period with no evidence of ischemia on SPECT myocardial perfusion imaging (N = 404). Hormonal status was defined as premenopausal (n = 78), postmenopausal (n = 277), and postmenopausal on hormone replacement therapy (HRT) (n = 49). Positive ECG response for ischemia was defined as I mm or greater horizontal and/or downsloping ST depression during and/or after exercise. The frequency of a positive ECG response to exercise without evidence of ischemia on gated SPECT imaging was analyzed according to hormonal status. Seventeen of 78 premenopausal women (22 %), 48 of 277 postmenopausal women (17 %), and 19 of 49 women taking HRT (39 %) had a positive ECG response. ECG positivity was significantly higher in HRT users when compared with premenopausal (P = .05) and postmenopausal women (P = .001). Conclusions. Exogenous estrogen replacement therapy affects ST-segment response to exercise, likely through a nonischemic mechanism. Unless HRT can be discontinued for a prolonged period of time (up to 6 weeks) prior to a stress test, myocardial imaging should be used to improve diagnostic accuracy.