4.5 Article

Age-related decrease in serum dihydrotestosterone concentration is accompanied by impaired vascular status

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EXPERIMENTAL GERONTOLOGY
卷 173, 期 -, 页码 -

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PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.exger.2023.112104

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Androgens; Sex steroids; Endothelium; Carotid artery intima -media thickness; Cardiovascular risk

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This study aimed to evaluate the effects of age-dependent alterations in serum dihydrotestosterone and its circulating metabolite on endothelial function and arterial stiffness. The results showed that older men had significantly lower levels of dihydrotestosterone and higher values of cIMT, AI, crPWV, and SI, indicating impaired arterial wall characteristics and worsened endothelial function. The concentration of dihydrotestosterone was negatively correlated with arterial wall parameters, markers of inflammation, and positively correlated with markers of endothelial function.
Introduction: The effect of androgens on the cardiovascular system in humans is ambiguous. Moreover, still little is known about the effects of the most potent androgen, dihydrotestosterone, on arterial stiffness and endothelial function. The aim of this study was to evaluate whether age-dependent alterations in serum concentration of dihydrotestosterone and its circulating metabolite are accompanied by changes in endothelial function and arterial stiffness.Methods: In 12 young and 11 older men, basal serum concentrations of testosterone, dehydroepiandrosterone sulfate (DHAE-S), androstenedione (AE), dihydrotestosterone (DHT) and androstanediol glucuronide (ADG) were analyzed in relation to vascular status including cIMT - carotid intima media thickness, cAI - central augmentation index, crPWV - carotid radial pulse wave velocity, SI - stiffness index, endothelial and inflammatory markers.Results: Although concentration of testosterone was not different between young and older group, it was demonstrated that DHT, DHEA-S, AE and ADG were significantly lower in older men in comparison to young men (p < 0.01). Interestingly the most surprising difference was found for DHT concentration, that was as much as 61 % lower in aged men that displayed significantly higher values of cIMT, AI, crPWV and SI (p < 10(-4)), suggestive of arterial stiffness. Furthermore, DHT was negatively correlated to all arterial wall parameters (cAI, crPWV, SI and cIMT), c-reactive protein (CRP) and hyaluronic acid (HA) concentration, as well as positively correlated to markers of endothelial function (MNA and 6-keto-PGF1 alpha) in all studied individuals (n = 23).Conclusions: We have shown that ageing leads to a significant decrease in DHT concentration that is accompanied by impaired arterial wall characteristics and worsened endothelial function. Therefore more attention should be paid to the DHT, DHEA-S and ADG concentrations as a biomarkers for vascular dysfunction in ageing men.

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