Impact of HRT on Exercise Training
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. In order 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 six months of one of three aerobic ET interventions or continued physical inactivity.
In 206 subjects, an insulin sensitivity index (SI) was obtained with a frequently sampled intravenous glucose tolerance test pre- and post-ET. Baseline and post-intervention 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 gender or HRT use influenced responses to exercise training. Linear modeling was used to determine if predictors for response in SI differed by gender or HRT use. Women who used HRT (HRT+) demonstrated significantly greater improvements in SI with ET than women not using HRT (HRT−). In those HRT+ women, plasma triglyceride change best correlated with change in SI. For HRT− women, capillary density change, and for men, subcutaneous adiposity change, best correlated with change in SI. In summary, in an ET intervention, HRT use appears associated with more robust responses in insulin action. Also, 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.
With the increasing prevalence of obesity and type 2 diabetes, efforts are focused on understanding the underlying pathogenesis of insulin resistance and how to improve insulin action with lifestyle efforts. It is well recognized that physical activity improves insulin action, reduces adiposity, enhances cardiorespiratory fitness, and induces a favorable lipoprotein particle distribution[2–5]. Also, exercise training has been found to alter a number of skeletal muscle parameters that may impact insulin action and glucose disposal[6–8].
In addition to exercise training, in post-menopausal women, HRT use can improve insulin action as well as adiposity, LDL and HDL cholesterol, and lean body mass despite paradoxical, yet clear evidence that chronic HRT use promotes adverse cardiovascular events[10–12]. Previously, we reported observations regarding the impact of specific exercise prescription effects on insulin sensitivity, where improvements with aerobic training were most dependent on the time spent training rather than the intensity of training in men and post-menopausal women. Here, in the context of a randomized controlled aerobic exercise intervention, STRRIDE (Studies of Targeted Risk Reduction Through Defined Exercise), our objective was to determine the impact of HRT use on insulin action response to exercise training. A secondary objective was to determine if physiologic characteristics unique to each group might account for any gender or HRT use differences in response in insulin action. Given that both exercise training and HRT use are associated with improvements in insulin action, we hypothesized that the combination of both would produce more robust responses in insulin sensitivity.