Sponsored by an educational grant from Ipsen
A decline of cognitive abilities as well as adverse mood shifts are observed in aging men, and hormonal effects on cerebral functions are a focus of interest. Androgens are especially important, as many men experience age-related alterations within the hypothalamic-pituitary-gonadal axis leading to late-onset hypogonadism. Several aspects have to be considered in this field. Firstly, a multitude of subdimensions exist concerning cognitive functions: memory has verbal and visuospatial properties, acute task-solving abilities comprise visuomotor capacities as well as processing visuospatial input, performing constructional tasks and verbal functions relate to fluency of recognition and output. Secondly, the associations of deteriorating cognitive functions with declining androgen concentrations, which are described by cross-sectional or longitudinal observation studies, have to be corroborated by interventional trials. Thirdly, testosterone undergoes aromatization to estradiol, which has properties of modulating cerebral functions on its own.
Indeed, observations and intervention trials in younger and aging hypogonadal men demonstrate that testosterone is directly and indirectly required for proper cerebral functioning. In regard to spatial cognition, functional neuroimaging demonstrates an androgen-induced activation of a distributed cortical network, the ventral processing stream. Spatial cognition in its various subdimensions is directly augmented by replenishment of androgen resources in hypogonadal men of any age, also shown by the experimental regimen of additional aromatase-inhibitors. Verbal abilities of these patients, as measured by tasks of memory and output fluency, experience an improvement during testosterone substitution as well; this process is most likely estrogen-mediated.
Testosterone levels and depressive disorders have been associated frequently: psychological symptoms of depression are observed in hypogonadal men and depressive patients often exhibit low androgen concentrations. Correspondingly, testosterone substitution can attenuate symptoms of depression in both groups of patients.
In conclusion, in hypogonadal men, testosterone substitution will contribute to improve the overall quality of life by positively affecting cognitive abilities and emotional well-being.
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