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The cardiac syndrome X is described as the triad of angina pectoris, a positive exercise test for myocardial ischemia, and angiographically smooth coronary arteries. Although syndrome X does not result in an increased risk of cardiovascular mortality, the symptoms are often troublesome and unresponsive to conventional antianginal therapy. The majority of patients are postmenopausal, and estrogen therapy can alleviate anginal symptoms. We investigated the effect of esterified estrogens combined with methyltestosterone (Estratest) on quality of life in postmenopausal women with syndrome X.Patients were withdrawn from antianginal therapy. Sublingual nitrates were allowed for treatment of anginal episodes. Patients underwent treadmill testing, and quality of life was assessed by using the Short Form-36 and Cardiac Health Profile questionnaires after the women had received 8 weeks of Estratest or identical placebo in a randomized, double-blind, cross-over study.Nineteen patients were randomized, and 16 patients completed the protocol. Plasma 17β-estradiol concentrations were significantly increased by Estratest; however, total testosterone levels were not. The “emotional” score of the Cardiac Health Profile questionnaire was significantly improved after Estratest use compared with placebo (p = 0.03); however, there was no significant change in the Short Form-36 questionnaire for any variable. Estratest significantly increased systolic blood pressure and rate pressure product at rest but had no effect on exercise parameters. Time to onset of chest pain during exercise was also unaffected.We have demonstrated a beneficial effect of Estratest on emotional well-being in postmenopausal women with cardiological syndrome X. There was no significant treatment effect on exercise parameters, including time to onset of chest pain.