Introduction
The interplay between obesity, testosterone replacement therapy (TRT), and brain health has garnered significant attention in recent years. Obesity and hypogonadism (low testosterone), both of which are common in older men, are associated with cognitive decline. This review aims to synthesize current research findings on how TRT, when combined with lifestyle interventions, affects cognitive functions in obese individuals with low testosterone levels.
Obesity and Cognitive Decline
Obesity is a well-documented risk factor for cognitive impairment and neurodegenerative diseases. Studies have shown that obesity can lead to brain insulin resistance, mitochondrial dysfunction, and increased neuroinflammation, all of which contribute to cognitive decline (3) (4). In animal models, diet-induced obesity has been linked to impaired hippocampal synaptic plasticity and cognitive functions (3) (4).
Testosterone Deficiency and Cognitive Function
Testosterone plays a crucial role in maintaining cognitive health. Testosterone deficiency has been associated with increased oxidative stress, reduced synaptic plasticity, and cognitive decline (7) (8). In testosterone-deprived male rats, cognitive impairments were observed earlier compared to their non-deprived counterparts, indicating the significant role of testosterone in brain health (3).
Combined Effects of Obesity and Testosterone Deficiency
The combination of obesity and testosterone deficiency appears to exacerbate cognitive decline. Studies in orchiectomized (removed testicles) obese rats have shown that these conditions together lead to more severe brain pathologies, including increased oxidative stress, inflammation, and synaptic dysfunction (3) (5). However, testosterone deprivation alone did not show additive or synergistic effects with obesity on cognitive impairment, suggesting that the mechanisms might be independent but converging on similar pathways (3).
Testosterone Replacement Therapy (TRT) and Cognitive Function
TRT has been investigated as a potential intervention to mitigate cognitive decline in hypogonadal men with obesity. Clinical trials have demonstrated that TRT, when combined with lifestyle interventions such as diet and exercise, can significantly improve cognitive functions. For instance, older men with obesity and hypogonadism showed improved global cognition, memory, and attention when treated with TRT alongside lifestyle modifications (1) (2). These improvements were linked to increased testosterone levels, enhanced insulin sensitivity, and reduced oxidative stress (1) (2). All of which is good for your quality and longevity of life.
Mechanisms of TRT in Cognitive Improvement
The beneficial effects of TRT on cognitive function are thought to be mediated through several mechanisms. TRT has been shown to improve brain insulin sensitivity, reduce oxidative stress, and enhance synaptic plasticity (6) (7).Â
Conclusion
The current body of research suggests that TRT, particularly when combined with lifestyle interventions, can significantly improve cognitive functions in obese individuals with low testosterone levels. These findings highlight the potential of TRT as a therapeutic strategy to mitigate cognitive decline in this high-risk population. Having good mental and physical health is of utmost importance as we age. See how Quali-T Men’s Health in Salem can help today!Â
References
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- Gregori, G., Celli, A., Barnouin, Y., Paudyal, A., Villareal, R., Quallas, C., & Villareal, D. (2020). 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. Journal of the Endocrine Society, 4. https://doi.org/10.1210/jendso/bvaa046.919.Â
- Pintana, H., Pratchayasakul, W., Sa-nguanmoo, P., Pongkan, W., Tawinvisan, R., Chattipakorn, N., & Chattipakorn, S. (2016). Testosterone deprivation has neither additive nor synergistic effects with obesity on the cognitive impairment in orchiectomized and/or obese male rats.. Metabolism: clinical and experimental, 65 2, 54-67 . https://doi.org/10.1016/j.metabol.2015.10.015.
- Jayaraman, A., Lent-Schochet, D., & Pike, C. (2014). Diet-induced obesity and low testosterone increase neuroinflammation and impair neural function. Journal of Neuroinflammation, 11. https://doi.org/10.1186/s12974-014-0162-y.Â
- Keawtep, P., Pratchayasakul, W., Arinno, A., Apaijai, N., Chunchai, T., Kerdphoo, S., Jaiwongkum, T., Chattipakorn, N., & Chattipakorn, S. (2019). Combined dipeptidyl peptidase-4 inhibitor with low-dose testosterone exerts greater efficacy than monotherapy on improving brain function in orchiectomized obese rats. Experimental Gerontology, 123, 45-56. https://doi.org/10.1016/j.exger.2019.05.008.Â
- Chunchai, T., Keawtep, P., Arinno, A., Saiyasit, N., Prus, D., Apaijai, N., Pratchayasakul, W., Chattipakorn, N., & Chattipakorn, S. (2020). A combination of an antioxidant with a prebiotic exerts greater efficacy than either as a monotherapy on cognitive improvement in castrated-obese male rats. Metabolic Brain Disease, 35, 1263 – 1278. https://doi.org/10.1007/s11011-020-00603-5.Â
- Pintana, H., Pongkan, W., Pratchayasakul, W., Chattipakorn, N., & Chattipakorn, S. (2015). Testosterone replacement attenuates cognitive decline in testosterone-deprived lean rats, but not in obese rats, by mitigating brain oxidative stress. AGE, 37. https://doi.org/10.1007/s11357-015-9827-4.
- Pintana, H., Chattipakorn, N., & Chattipakorn, S. (2015). Testosterone deficiency, insulin-resistant obesity and cognitive function. Metabolic Brain Disease, 30, 853 – 876. https://doi.org/10.1007/s11011-015-9655-3.
