Aims: We examined interaction of sex steroid hormones and obesity with regard to insulin resistance (IR) and type 2 diabetes (T2D) by using nationally representative data from the US. Methods: Data of 1461 men aged >= 20 years who participated in the Third National Health and Nutrition Examination Survey were analyzed. Multiplicative interaction was calculated by cross-product interaction terms in multivariable logistic regression models. Additive interaction was assessed by the relative excess risk due to interaction (RERI). Results: After adjusting for demographic and lifestyle covariates, the odds of IR were greatest among obese men with low free testosterone and high androstanediol glucuronide. Multiplicative interactions for total testosterone, free testosterone, and free estradiol index (FEI) were statistically significant with central obesity but not with overweight and obesity regarding to T2D (P < 0.05). Significant additive interactions with obesity or central obesity were detected for total testosterone (RERI = 2.75, 95% CI = 0.92,4.59), SHBG (RERI = 5.71, 95% CI = 0.77,10.64), and FEI (RERI = -9.96, 95% CI = -19.18,-0.74) with regard to IR, beta-cell dysfunction, and T2D. Conclusions: Our findings add to the evidence suggesting that low testosterone and high estradiol may be associated greater risks of IR and 120 by interacting with overall and central obesity in adult men. (C) 2017 Published by Elsevier Inc.