A direct association between BMI and hsCRP was observed across demographic variables such as age, sex, ethnicity, and education. Further evidence comes from studies involving individuals with schizophrenia, where BMI and hsCRP have been linked to abnormal lipid profiles (25). Among overweight or obese individuals and smokers, those who were constantly active also had a lower likelihood of elevated hsCRP levels compared to their physically inactive peers. Moreover, only one subject presented with T and fT concentrations slightly below the healthy adult male reference ranges, but even in this case, a late-onset hypogonadism (LOH) syndrome was not diagnosed because there were no symptoms suggestive of testosterone deficiency see, e.g., (13). Blood for serum CRP, AAG, FER, IL-6, total cholesterol (TC), triglycerides (TG), low- and high-density lipoproteins (LDL and HDL, respectively), total T, cortisol (C), and sex hormone-binding globulin (SHBG) concentrations was collected into plain tubes and left to clot for a minimum of 30 min at room temperature and then centrifuged at 4,000 rpm for 5 min. Studies concerning the relationship between androgens and inflammation have so far mainly focused on the inflammatory cytokines such as interleukin-1 (IL-1), IL-6, and TNF-α (4). What is interesting is that a heavy exercise training program is thought to unfavorably affect the T concentration (18) and the pro- and anti-inflammatory balance (19), whereas moderate training loads were linked to both enhanced gonadal androgen concentrations (20) and anti-inflammatory state (21). The possible influence of body fat content on the relationship between androgen and inflammatory status also indicates that the level of physical activity could be of paramount importance in this connection. One may speculate that a moderately higher level of physical activity affects positively both the testosterone and HDL concentrations, however, recent data have indicated that a more important risk factor for cardiovascular events is HDL cholesterol efflux capacity (63), which could be influenced by gonadal androgens (64). Taking into account that we have reported a significant positive correlation between the AAG concentration and BMI see Table 2 and "Results" in (11), one may suggest that a higher body fat stimulates AAG production by hepatocytes through the secretion of pro-inflammatory cytokines, mainly TNF-α and IL-6. The negative relationship between T concentration and fat mass has often been demonstrated (31, 32). The significant bivariate correlations between BMI and the markers of both androgen and inflammatory profiles (see Table 2) support such conclusions. The reduced physical activity might, in turn, further compromise systemic T availability and contribute to the unfavorable changes in the inflammation and blood lipid profile. Therefore, it can be postulated that a low-to-moderate training load leads to an increase in the T concentration (20, 54), a moderate-to-heavy training load does not change it (26), and a heavy-to-maximal training load leads to a decrease in its concentration (55). The data regarding the effect of exercise training on gonadal androgens in aging males are, however, inconsistent (52, 53). However, Sartorius et al. (51) reported that, in aged men characterized by "very good or excellent" health, serum sex steroids are not reduced. It seems that the role of AAG in inflammatory progression needs to be further investigated, also in view of the recent data that demonstrated the importance of IL-6 and IL-6R (interleukin-6 receptor) in cardiovascular diseases (46, 47). It should also be mentioned that AAG was demonstrated to maintain metabolic homeostasis and to suppress inflammatory processes (44), similar to the functions of IL-6 and CRP that may also be elevated in the absence of an inflammatory state and exert anti-inflammatory effects, as recently reviewed by Del Giudice and Gangestad (45). This effect may occur through a testosterone-induced decrease of the expression of Toll-like receptor 4 (TLR4), which is known to stimulate different signaling pathways such as the NF-κB pathway (39). Rotter I, Ciosek Ż, Syroka A and Ryl A (2025) A cross-sectional study of testosterone deficiency and inflammatory markers in older men. Moreover, the positive correlation between testosterone and physical activity level suggests that exercise training may reduce the age-related decrease in gonadal androgens, which seems to be one of the main beneficial effects (anti-inflammatory one) of physical activity in aging men. Based on the above literature data, it may be inferred that the correlation between androgens and inflammatory markers observed in this study is not accidental. BMI, body mass index; T, testosterone; fT, free testosterone; fT/C, free testosterone-to-cortisol ratio; CRP, C-reactive protein; AAG, alpha-1-acid glycoprotein; FER, ferritin; IL-6, interleukin-6; LDL, low-density lipoprotein; HDL, high-density lipoprotein; TG, triglycerides; β, standardized beta coefficient; p, significance value; aR2, adjusted coefficient of determination. The associations between fT and fT/C ratio and IL-6 concentration observed in the bivariate analysis (Figure 2) were no longer significant when controlling for other covariates (age, lipid profile, and BMI) (see Table 3). However, when adjustment for BMI was made (model 3), these associations stayed significant only for the androgen profile variables and the AAG concentrations (see Table 3). BMI, body mass index; CRP, C-reactive protein; AAG, alpha-1-acid glycoprotein; FER, ferritin; IL-6, interleukin-6; TC, total cholesterol; LDL, low-density lipoprotein; HDL, high-density lipoprotein; non-HDL, non-high-density lipoprotein; TG, triglycerides; T, testosterone; fT, free testosterone; fT/C, free testosterone-to-cortisol ratio. The only exceptions were a non-significant correlation between age and the AAG concentration and between age and the HDL concentration (see Table 2). In this study, the bivariate correlations were evaluated using Spearman’s correlation coefficient because of the non-normal distribution of the inflammatory and lipid profile variables and the time spent on physical activity.
