Lowered Serum Testosterone Concentration Is Associated With Enhanced Inflammation and Worsened Lipid Profile in Men

Abstract

The negative relationship between testosterone and inflammatory cytokines has been reported for decades, although the exact mechanisms of their interactions are still not clear. At the same time, little is known about the relation between androgens and acute phase proteins. Therefore, in this investigation, we aimed to study the relationship between androgen status and inflammatory acute phase reactants in a group of men using multi-linear regression analysis. Venous blood samples were taken from 149 men ranging in age from 18 to 77 years. Gonadal androgens [testosterone (T) and free testosterone (fT)], acute phase reactants [C-reactive protein (CRP), ferritin (FER), alpha-1-acid glycoprotein (AAG), and interleukin-6 (IL-6)], cortisol (C), and lipid profile concentrations were determined. It was demonstrated that the markers of T and fT were negatively correlated with all acute phase proteins (CRP, FER, and AAG; p < 0.02) and the blood lipid profile [total cholesterol (TC), low-density lipoprotein (LDL), and triglycerides (TG); p < 0.03]. Multivariate analysis showed that T, fT, and the fT/C ratio were inversely correlated with the CRP, AAG, and FER concentrations independently of age and blood lipids. When adjustment for BMI was made, T, fT, and the fT/C ratio were negatively correlated with the AAG concentrations only. In addition, it was demonstrated that gonadal androgens were positively correlated with physical activity level (p < 0.01). We have concluded that a lowered serum T concentration may promote inflammatory processes independently of adipose tissue and age through a reduced inhibition of inflammatory cytokine synthesis, which leads to enhanced acute phase protein production. Therefore, a low serum T concentration appears to be an independent risk factor in the development of atherosclerosis and cardiovascular diseases. Moreover, the positive correlation between testosterone and physical activity level suggests that exercise training attenuates the age-related decrease in gonadal androgens and, in this way, may reduce the enhancement of systemic low-grade inflammation in aging men.

Protection against Osteoarthritis Symptoms by Aerobic Exercise with a High-Protein Diet by Reducing Inflammation in a Testosterone-Deficient Animal Model

“…In a systemic review, long-term soccer training is positively associated with changes in serumfree testosterone concentrations and negatively related to the serum cortisol concentration in professional soccer players [33]. In men, the serum testosterone concentrations are positively associated with physical activity and negatively related to inflammation [34]. On the other hand, the present study did not show a positive association of serum testosterone concentrations with exercise in ORX rats, even though exercise lowered inflammation.…”

Could Lower Testosterone in Older Men Explain Higher COVID-19 Morbidity and Mortalities?

“…The role of sex hormones has been extensively studied in physiological and pathological settings. Low levels of circulating TEST are associated with an increased cardiovascular risk by leading to an increase in inflammation, impaired metabolism, and mitochondrial dysfunction [99,100].…”

“…In other works, there is evidence that after 2 or 16 weeks of GDX, a decrease in levels of mRNA of NCX occurs and that it could be reversed with supplementation of The role of sex hormones has been extensively studied in physiological and pathological settings. Low levels of circulating TEST are associated with an increased cardiovascular risk by leading to an increase in inflammation, impaired metabolism, and mitochondrial dysfunction [99,100].…”

“…Another aspect that has gained interest is the synchronicity between the decline of TEST plasmatic concentration and the development of a pro-inflammatory state [100]. In male diabetic patients, low levels of TEST are associated with a pro-inflammatory condition characterized by high TNF-α concentrations, an impaired metabolic profile, and mitochondrial dysfunction, leading to an increase in cardiovascular risk [99].…”

Interplay between Inflammation and Pathological Bone Resorption: Insights into Recent Mechanisms and Pathways in Related Diseases for Future Perspectives

“…A deficit of estrogen in postmenopausal women and a deficit estrogen, testosterone and other androgens in elderly men contribute to the development of osteoporosis, since these hormones play a regulatory role in inflammation and bone remodeling. Aging is known to be accompanied by a decrease in several physiological functions and is accompanied by an increase in metabolic risk and systematic inflammation, namely pro-inflammatory cytokines and oxidative stress [120][121][122]. More importantly, cellular senescence associated with aging is a dynamic process in which cells lose their proliferative potential, undergo irreversible growth arrest in response to stressors and stimuli and promote a distinctive proinflammatory secretome, termed the senescence-associated secretory phenotype (SASP).…”