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The aim of this study was to examine whether obesity modifies the effects of endogenous steroid sex hormones on arterial calcification in women at midlife.Associations between estradiol, testosterone, sex hormone-binding globulin, and free androgen index and the presence and extent of coronary and aortic calcification were evaluated in 187 obese (body mass index, ≥30 kg/m2) and 281 nonobese (body mass index, <30 kg/m2) women from the Study of Women's Health Across the Nation. Logistic and linear regressions were used as appropriate.Prevalence rates of coronary and aortic calcification were significantly higher among obese compared with nonobese women (P < 0.001, for both). In multivariable analyses, steroid sex hormones were not associated with the presence of coronary calcification. However, for the extent of coronary calcification, significant interactions were found between obesity and both sex hormone-binding globulin (P < 0.0001) and free androgen index (P = 0.008). In nonobese women, higher sex hormone-binding globulin (P = 0.0006) and lower free androgen index (P = 0.01) were associated with a greater extent of coronary calcification, whereas lower sex hormone-binding globulin was associated with greater extent of coronary calcification in obese women (P = 0.05). For aortic calcification outcomes, higher sex hormone-binding globulin was associated with the presence of aortic calcification among nonobese women (odds ratio, 1.64; 95% CI, 1.16-2.32, for each 1-SD greater sex hormone-binding globulin).Associations between endogenous steroid sex hormones and arterial calcification vary by obesity status among perimenopausal women. Further research is needed to better understand the possible mechanisms of these associations.