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The presence of peripheral fat mass (PFM) appears to counteract the atherogenic trends of central fat mass through mechanisms presently poorly understood. In elderly women with distinct forms of body fat distribution, we wanted to study whether physical activity and aortic calcification are related to plasma levels of cortisol, 17-α-hydroxyprogesterone (17-α-OHP), dehydroepiandrosterone (DHEA), androstenedione (ASD), and interleukin 6 (IL6) accomplishing an anti-atherogenic milieu. A total of 276 well-defined generally healthy women aged 60–85 years were included. Categorization of body fat distribution was based on the relative presence of central to PFM measured by dual-energy X-ray absorptiometry. Women meticulously reported weekly physical activity. Outcome measures were aortic calcification between lumbar vertebra L1 and L4, plasma levels of hormones, and IL6. In peripheral adipose women, plasma DHEA and ASD increased with the degree of physical activity. This was also mirrored in the ratios of cortisol/DHEA and cortisol/17-α-OHP. Peripheral adipose women with high DHEA relative to cortisol had less severe aortic calcification, and in the same group a higher level of physical activity was associated with lower levels of plasma IL6. In conclusion, this study demonstrates that high physical activity is associated with a high circulating androgen to cortisol ratio, low IL6, and less severe aortic calcification. Since androgens inhibit IL6 secretion, the activity-induced increase of these hormones might be an anti-atherogenic signal. [ABSTRACT FROM AUTHOR]