Center for Translational Research on Inflammatory Diseases, Michael E DeBakey VA Medical Center, Houston, TX, USA.
Division of Endocrinology, Diabetes, and Metabolism, Baylor College of Medicine, Houston, TX, USA.
Am J Clin Nutr. 2021 Nov 8;114(5):1590-1599. doi: 10.1093/ajcn/nqab253.
Both obesity and hypogonadism are common in older men which could additively exacerbate age-related declines in cognitive function. However, little is known about the effects of lifestyle intervention plus testosterone replacement therapy in this population.
In this secondary analysis of the LITROS (Lifestyle Intervention and Testosterone Replacement in Obese Seniors) trial, we examined whether testosterone replacement therapy would improve cognitive function when added to intensive lifestyle intervention in older men with obesity and hypogonadism.
Eighty-three older, obese hypogonadal men with frailty were randomly assigned to lifestyle therapy (weight management and exercise training) plus testosterone (LT + Test) or lifestyle therapy plus placebo (LT + Pbo) for 6 mo. For this report, the primary outcome was change in the global cognition composite z score. Secondary outcomes included changes in z score subcomponents: attention/information processing, memory, executive function, and language. Changes between groups were analyzed using mixed-model repeated-measures ANCOVAs following the intention-to-treat principle.
Global cognition z score increased more in the LT + Test than in the LT + Pbo group (mean change: 0.49 compared with 0.21; between-group difference: -0.28; 95% CI: -0.45, -0.11; Cohen's d = 0.74). Moreover, attention/information z score and memory z score increased more in the LT + Test than in the LT + Pbo group (mean change: 0.55 compared with 0.23; between-group difference: -0.32; 95% CI: -0.55, -0.09; Cohen's d = 0.49 and mean change: 0.90 compared with 0.37; between-group difference: -0.53; 95% CI: -0.93, -0.13; Cohen's d = 1.43, respectively). Multiple regression analyses showed that changes in peak oxygen consumption, strength, total testosterone, and luteinizing hormone were independent predictors of the improvement in global cognition (R2 = 0.38; P < 0.001).
These findings suggest that in the high-risk population of older men with obesity and hypogonadism, testosterone replacement may improve cognitive function with lifestyle behaviors controlled via lifestyle intervention therapy.This trial was registered at clinicaltrials.gov as NCT02367105.
肥胖和性腺功能减退在老年男性中很常见，这可能会加剧与年龄相关的认知功能下降。然而，关于生活方式干预加睾丸激素替代疗法在这一人群中的效果知之甚少。
在肥胖老年人的生活方式干预和睾丸激素替代治疗（LITROS）试验的二次分析中，我们研究了在肥胖和性腺功能减退的老年男性中，睾丸激素替代疗法在强化生活方式干预的基础上是否会改善认知功能。
83 名年龄较大、肥胖、性腺功能减退、虚弱的男性随机分为生活方式治疗组（体重管理和运动训练）加睾丸酮（LT+Test）或生活方式治疗加安慰剂（LT+Pbo），治疗 6 个月。在本报告中，主要结局是全球认知综合 z 评分的变化。次要结局包括 z 评分亚成分的变化：注意力/信息处理、记忆、执行功能和语言。采用混合模型重复测量方差分析（根据意向治疗原则）分析组间变化。
LT+Test 组的全球认知 z 评分比 LT+Pbo 组增加更多（平均变化：0.49 比 0.21；组间差异：-0.28；95%置信区间：-0.45，-0.11；Cohen's d=0.74）。此外，LT+Test 组的注意力/信息处理 z 评分和记忆 z 评分比 LT+Pbo 组增加更多（平均变化：0.55 比 0.23；组间差异：-0.32；95%置信区间：-0.55，-0.09；Cohen's d=0.49）和记忆 z 评分（平均变化：0.90 比 0.37；组间差异：-0.53；95%置信区间：-0.93，-0.13；Cohen's d=1.43）。多元回归分析显示，峰值摄氧量、力量、总睾酮和黄体生成素的变化是全球认知改善的独立预测因素（R2=0.38；P<0.001）。
这些发现表明，在肥胖和性腺功能减退的老年男性高危人群中，睾丸激素替代疗法可能通过生活方式干预治疗来改善认知功能。本试验在 clinicaltrials.gov 注册为 NCT02367105。
