Although functions of dehydroepiandrosterone (DHEA) and its sulfate ester are unknown, investigators have found an inverse relation between DHEA-sulfate levels and coronary artery disease, suggesting its importance as an inverse coronary risk factor. In previous studies, where behavioral therapy was used to try to reduce stress and social isolation, DHEA levels increased--although other confounding factors, including enhanced physical activity, also were affected. To determine the influence of physical activity alone on plasma DHEA-sulfate levels in patients with coronary artery disease, the authors studied the effects of exercise training by measuring plasma DHEA-sulfate levels and other parameters in 96 patients at baseline and after 12 weeks of cardiac rehabilitation and exercise training. They confirmed that DHEA-sulfate levels decreased with age (r = 0.41; P < 0.0001) and that DHEA-sulfate levels correlated with body mass index (r = 0.32; P < 0.001), but not with other baseline risk factors. Exercise training during cardiac rehabilitation resulted in a 43% increase in exercise capacity (P < 0.0001) and was associated with improvement in other cardiac risk factors; however, there were no significant changes in plasma DHEA-sulfate levels (106 +/- 77 micrograms/dL versus 102 +/- 76 micrograms/dL). Although behavior therapy in combination with exercise training was shown to lead to concomitant increases in DHEA-sulfate and physical activity, exercise training alone has no significant impact on DHEA-sulfate, thereby strengthening the suggested role of behavioral changes in modifying this hormone.