Impact of hormone replacement therapy on exercise training-induced improvements in insulin action in sedentary overweight adults

Exercise training (ET) and hormone replacement therapy (HRT) are both recognized influences on insulin action, but the influence of HRT on responses to ET has not been examined. To determine if HRT use provided additive benefits for the response of insulin action to ET, we evaluated the impact of HRT use on changes in insulin during the course of a randomized, controlled, aerobic ET intervention. Subjects at baseline were sedentary, dyslipidemic, and overweight. These individuals were randomized to 6 months of one of 3 aerobic ET interventions or continued physical inactivity. In 206 subjects, an insulin sensitivity index (S_I) was obtained with a frequently sampled intravenous glucose tolerance test pre- and post-ET. Baseline and postintervention fitness, regional adiposity, general adiposity, skeletal muscle biochemistry and histology, and serum lipoproteins were measured as other putative mediators influencing insulin action. Two-way analyses of variance were used to determine if sex or HRT use influenced responses to exercise training. Linear modeling was used to determine if predictors for response in S_I differed by sex or HRT use_. Women who used HRT (HRT+) demonstrated significantly greater improvements in S_I with ET than women not using HRT (HRT-). In those HRT+ women, plasma triglyceride change best correlated with change in S_I. For HRT- women, capillary density change and, for men, subcutaneous adiposity change best correlated with change in S_I. In summary, in an ET intervention, HRT use appears to be associated with more robust responses in insulin action. Furthermore, relationships between ET-induced changes in insulin action and potential mediators of change in insulin action are different for men, and for women on or off HRT. These findings have implications for the relative utility of ET for improving insulin action in middle-aged men and women, particularly in the setting of differences in HRT use.