Testosterone, Depression, and Cognitive Impairment in Men: an Attempt at Practical Analysis

Abstract

Cognitive impairment (CI) accompanies the aging process and is manifested by difficulties with memorization, learning, concentration and decision-making, which greatly complicates the daily life of the suffering subject. In addition, medical care and social adaptation of these patients are costly and put a significant strain on the health care system. According to a forecast by G. Corona’s group, the number of people with CIs will increase significantly in the coming years, reaching 131.5 million by 2030. To date, a significant amount of researches has been conducted to uncover the mechanisms of development and risk factors of CI in order to develop effective prevention and treatment programs. Age-related decline in testosterone levels are among the potentially modified risk factors of СI. The objective: to analyze the role of testosterone in pathogenesis of cognitive impairment and depression and the possibilities of testosterone therapy to correct them. Materials and methods. Evidence was collected from the study publications and meta-analyzes exploring the role of testosterone in pathogenesis, prevention and correction of cognitive impairment and depression over the past five years and preliminary analysis of data from our own study involving 547 men with hormonal disorders. Results. Cerebral vessels are the target for the direct (via androgen receptors) and indirect (via influence on cardiovascular risk factors) action of androgens. The testosterone insufficiency is associated with both metabolic and cardiovascular disorders (hypertension, diabetes, hyperlipidemia, obesity), as well as depression and CI. Serum-free-testosterone and free testosterone index are the most sensitive biomarkers of testosterone insufficiency in patients with depression and CI. The corrective effect of testosterone therapy (TT) on depression and CI depends on their severity and levels of androgens: a clinically and statistically significant effect was registered in mild disorders with androgen deficiency. The findings of the meta-analysis do not support the use of TT for improving attention, memory (working, verbal, visual), executive function, speech, visual-motor and visual-spatial abilities in subjects with eugonadism and hypogonadism. According to preliminary analysis of the results of our study, the nature of psycho-emotional disorders is determined by the sexual constitution (SC): weak type of SC (feminine men) is associated with the higher incidence of anxiety, the strong type of SC – with propensity for depression, the middle type of SC – with aggression. Thus, testosterone, estrogens, vasopressin, and adrenaline levels should be measured in patient with aggression. Conclusions. Despite the importance of androgens for mood and cognitive functions, and their synchronous decline during the aging process, the place of TT in the prevention/ correction of whole spectrum of CIs is still unclear. It is obvious now that TT can be justified in patients with mild disorders and proven androgen signal attenuation, but in most cases has no independent meaning. Further studies to find optimal TT indications and regimes are mandatory.