Oxidative Stress and Inflammation Are Associated With Age-Related Endothelial Dysfunction in Men With Low Testosterone

Vascular aging, including endothelial dysfunction secondary to oxidative stress and inflammation, increases the risk for age-associated cardiovascular disease (CVD). Low testosterone in middle-aged/older men is associated with increased CVD risk. We hypothesized that low testosterone contributes to...

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Published in:The journal of clinical endocrinology and metabolism Vol. 107; no. 2; p. e500
Main Authors: Babcock, Matthew C, DuBose, Lyndsey E, Witten, Teresa L, Stauffer, Brian L, Hildreth, Kerry L, Schwartz, Robert S, Kohrt, Wendy M, Moreau, Kerrie L
Format: Journal Article
Language:English
Published: United States 01.02.2022
Subjects:
Adolescent
Adult
Aged
Aging - blood
Aging - immunology
Aging - metabolism
Blood Flow Velocity
Cardiovascular Diseases - epidemiology
Cardiovascular Diseases - immunology
Cardiovascular Diseases - metabolism
Cardiovascular Diseases - physiopathology
Cross-Sectional Studies
Endothelium, Vascular - diagnostic imaging
Endothelium, Vascular - physiopathology
Heart Disease Risk Factors
Humans
Male
Middle Aged
Oxidative Stress - immunology
Plethysmography
Testosterone - blood
Testosterone - deficiency
Ultrasonography, Doppler
Young Adult
endothelial function
aging
andropause
testosterone
inflammation
oxidative stress
ISSN:1945-7197, 1945-7197
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Summary:Vascular aging, including endothelial dysfunction secondary to oxidative stress and inflammation, increases the risk for age-associated cardiovascular disease (CVD). Low testosterone in middle-aged/older men is associated with increased CVD risk. We hypothesized that low testosterone contributes to age-associated endothelial dysfunction, related in part to greater oxidative stress and inflammation. This cross-sectional study included 58 healthy, nonsmoking men categorized as young (N = 20; age 29 ± 4 years; testosterone 500 ± 58 ng/dL), middle-aged/older with higher testosterone (N = 20; age 60 ± 6 years; testosterone 512 ± 115 ng/dL), and middle-aged/older lower testosterone (N = 18; age 59 ± 8 years; testosterone 269 ± 48 ng/dL). Brachial artery flow-mediated dilation (FMDBA) was measured during acute infusion of saline (control) and vitamin C (antioxidant). Markers of oxidative stress (total antioxidant status and oxidized low-density lipoprotein cholesterol), inflammation (interleukin [IL]-6 and C-reactive protein [CRP]), and androgen deficiency symptoms were also examined. During saline, FMDBA was reduced in middle-aged/older compared with young, regardless of testosterone status (P < 0.001). FMDBA was reduced in middle-aged/older lower testosterone (3.7% ± 2.0%) compared with middle-aged/older higher testosterone (5.7% ± 2.2%; P = 0.021), independent of symptoms. Vitamin C increased FMDBA (to 5.3% ± 1.6%; P = 0.022) in middle-aged/older lower testosterone but had no effect in young (P = 0.992) or middle-aged/older higher testosterone (P = 0.250). FMDBA correlated with serum testosterone (r = 0.45; P < 0.001), IL-6 (r = -0.41; P = 0.002), and CRP (r = -0.28; P = 0.041). Healthy middle-aged/older men with low testosterone appear to have greater age-associated endothelial dysfunction, related in part to greater oxidative stress and inflammation. These data suggest that low testosterone concentrations may contribute to accelerated vascular aging in men.
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ISSN:1945-7197
1945-7197
DOI:10.1210/clinem/dgab715