Abstract P153: Intensive Lifestyle Intervention in Type 2 Diabetes Mellitus Results in a More Favorable Sex Hormone Profile in Both Post-Menopausal Females and Older Males (The Look AHEAD Trial Sex Hormone Study)

Background: Prior studies showed an association between some adverse cardiometabolic outcomes and lower testosterone in males and higher estrogen in both males and post-menopausal females. However, few studies of sex hormones focused on people with type 2 diabetes (T2DM), assessed hormone changes over time or applied highly sensitive laboratory assays. Given the importance of lifestyle modification (i.e., diet, exercise and weight loss) in preventing cardiometabolic complications in people with T2DM, we examined the impact of an Intensive Lifestyle Intervention (ILI) on sex hormones over time and differences by sex. Methods: The Look AHEAD (Action for Health in Diabetes) Study was a randomized control trial of 5,145 individuals with BMI ≥25 and T2D to evaluate the effect of ILI compared to the Diabetes Support and Education (DSE) control group on incident cardiovascular events. We selected a sample of 472 males and 426 post-menopausal female participants (mean age 60 years [SD 6.3], 20.5% Black) to examine sex hormones (estradiol - E2, total testosterone - T) and sex hormone binding globulin (SHBG) at baseline and year 1. E2 and T were measured using mass spectrometry analysis and SHBG was measured using an immunoassay. Results: In males, ILI increased SHBG by 17.3% and T by 10.6% compared to the DSE group (Table). In postmenopausal females, ILI increased SHBG by 12.0% and decreased E2 by 23.4% compared to the DSE group (Table). The change in the sex hormone levels from baseline to 1-year follow up was attenuated when adjusted for change in BMI. Conclusion: ILI resulting in weight loss increased T in males and decreased E2 in postmenopausal females and increased SHBG in both sexes. We plan further analysis with a larger sample and longer follow-up to examine the role of weight loss either as a co-occurring metabolic process or as a mediator for the change in sex hormones to better understand the impact of lifestyle changes and sex diffrences.