OR02-05 Effect of Testosterone Replacement Therapy Added to Intensive Lifestyle Intervention on Cognitive Functions in Frail, Older Veterans with Hypogonadism and Obesity: A Randomized Clinical Trial

Background: Both hypogonadism and obesity are common in older men which might additively exacerbate their age-related decline in cognitive functions. We tested the hypothesis that the addition of testosterone replacement therapy to intensive lifestyle intervention would enhance the benefits of intensive lifestyle intervention on cognition in older men with hypogonadism and obesity. Methods: Eighty-three older (age≥65 years) male veterans with obesity (BMI≥30 kg/m(2)) and evidence of persistently low AM testosterone (<300 ng/dl) associated with frailty (modified Physical Performance Test score <31) were randomized to six months of: 1) lifestyle therapy (diet-induced weight loss and supervised aerobic and resistance exercise training) + testosterone replacement therapy (LT+Test) or 2) lifestyle therapy + placebo (LT+Pbo). In this secondary analyses, outcomes were changes in cognition as assessed through comprehensive cognitive test battery (Modified Mini-Mental State Exam, Word Fluency Test, Trail Making Test Parts A and B Rey Auditory Verbal Learning Test, Stroop Color and Word Test, and Symbol Digit Modalities Test). We used z scores of changes in the cognitive tests to assess changes in attention, memory, executive function, language, global, and composite cognitive functions in response to the lifestyle and hormonal interventions. Results: After 6 months, body weight decreased similarly in the LT+Test group and LT+Pbo group (decrease of 9.7 kg vs. 10.3 kg, respectively; P=0.91) whereas testosterone levels increased more in the LT+Test than in the LT+Pbo group (increase of 324 ng/dl vs 88 ng/dl, respectively; P<0.001). Memory z-score increased more in the LT+Test group than in the LT+Pbo group (0.73 vs. 0.39, respectively; P=0.03). Moreover, attention z-score increased more in the LT+Test group than in the LT+Pbo group (0.89 vs. 0.38, respectively; P=0.01). On the other hand, changes in executive function z-score, language z-score, and global z-score did not significantly differ between the LT+Test group and LT+Pbo group (0.45 vs 0.37, 0.34 vs 0.07, and 0.55 vs 0.29, respectively; P=0.13 to 0.56). More importantly, the composite cognitive z-score obtained by averaging all z-scores from each domain increased more in the LT+Test group than in the LT+Pbo group (0.56 vs 0.27; P=0.003). Conclusion: These findings suggest that in the specific population of older men with hypogonadism and obesity associated with frailty, testosterone replacement therapy can augment the positive effects on cognition from intensive lifestyle intervention by diet-induced weight loss and combined aerobic and resistance exercise.