This study utilized data from the NHANES in the United States to investigate the association between serum testosterone levels and CHF in adult males. The results of the study demonstrated a linear relationship between low serum testosterone levels and CHF, with an increasing serum testosterone level being associated with a gradual reduction in the risk of CHF. After adjusting for other potential confounding factors, high serum testosterone levels remained significantly negatively correlated with CHF. Subgroup analysis revealed that this significant reduction in the proportion of CHF individual associated with high serum testosterone levels was only observed in the population aged 50 years and above.

Numerous studies have delved into the potential links between endogenous sex hormones, particularly serum testosterone, and cardiovascular disease (CVD). While CVD is a well-established global health concern, the association between serum testosterone and heart failure (HF) is still under investigation. The findings from existing studies, however, yielded inconsistent results, highlighting the necessity for further exploration in this area. In the context of men, an examination of a subset of participants in the Atherosclerosis Risk in Communities (ARIC) study did not uncover a statistically significant correlation between serum testosterone levels and the development of HF over a period of 12.8 years [8]. However, a separate and intriguing mendelian randomization study conducted using extensive data from the UK Biobank demonstrated a positive association between genetically predicted serum testosterone levels and the risk of incident HF [9]. These findings suggest a potential role of serum testosterone in influencing HF risk in men. Shifting our focus to women, the Multi-Ethnic Study of Atherosclerosis (MESA) did not observe any statistically significant associations between total serum testosterone, dehydroepiandrosterone (DHEA), sex hormone-binding globulin (SHBG) levels, and incident HF [10]. Nonetheless, total serum testosterone was identified as being positively associated with incident CVD and coronary heart disease (CHD) in women. Interestingly, DHEA exhibited an inverse relationship with HF with reduced ejection fraction (HFrEF), implying a potential protective effect against this specific type of HF. Furthermore, a similar mendelian randomization study conducted utilizing the UK Biobank data did not identify an association between genetically predicted serum testosterone levels and incident HF among women [9].

Serum testosterone was a crucial hormone involved in the development of heart failure, and it may have diverse effects on the cardiovascular system. Increased serum testosterone levels were associated with a decreased risk of heart failure, partially due to its protective effects on the vascular system [2]. Research suggested that serum testosterone could help prevent the development of conditions like atherosclerosis and thrombosis by reducing the release of inflammatory cytokines, improving endothelial function, stabilizing plaques, and reducing carotid intima-media thickness. Moreover, elevated serum testosterone levels in males were linked to lower blood pressure, reduced obesity, decreased left ventricular volume, and a lower risk of developing diabetes - all of which contributed to a decreased risk of heart failure. However, it’s important to note that serum testosterone could also have adverse effects on the cardiovascular system [11]. It possessed pro-inflammatory and vasoconstrictive properties, which may lead to increased blood pressure and other vascular abnormalities. Additionally, serum testosterone may promote the growth of muscle cells, potentially resulting in cardiac cell hypertrophy and myocardial thickening, which were commonly observed in heart failure with preserved ejection fraction. Postmenopausal women with elevated serum testosterone levels showed an increased risk of metabolic syndrome, endothelial dysfunction, atherosclerosis, and chronic heart disease. The associations in males, however, remained less clear. Understanding the cardiovascular effects of serum testosterone in specific populations was complex and currently inconclusive. Individual variations, coupled with other factors like metabolic status, hormone metabolism, and cardiovascular rehabilitation, likely influenced the effects of serum testosterone [12]. Therefore, while there appeared to be an association between increased serum testosterone levels and a lower risk of heart failure, further research was necessary to delineate the specific mechanisms and applicability of these findings.

An interesting finding in this study revealed an association between serum testosterone levels and the higher proportion of CHF exclusively among male individuals aged fifty and above. Conversely, no such association was observed in the population aged below fifty. The reason for this difference might be that the number of individuals in Q1 group in the population below 50 years old is relatively small compared to the other three groups, which results in a lack of statistically significant P value. We found that as the serum testosterone level increases, the obtained OR decreases, and the OR value of Q4 group in the population below 50 years old was also less than that in the population above 50 years old. It might be necessary to analyze a larger population of male individuals below 50 years old in the future to validate our research findings.

Low serum testosterone levels in men were associated with a significantly higher risk of CHF, potentially serving as an early warning indicator for this condition. Furthermore, there was a linear negative correlation between serum testosterone levels and the occurrence of CHF, indicating that higher serum testosterone levels were associated with a lower risk of developing CHF [13, 14]. This association was particularly significant in individuals aged 50 and older. These findings had important implications for clinical practice, as serum testosterone levels could serve as an adjunctive marker for predicting and diagnosing heart failure. For patients with low serum testosterone levels, further cardiovascular assessment and interventions may have been necessary to prevent the progression of heart failure. Additionally, maintaining appropriate serum testosterone levels may have helped prevent the onset of heart failure, especially in men aged 50 and above. However, to better understand the relationship between serum testosterone and heart failure, further research was needed to validate and explore the underlying mechanisms. Therefore, before incorporating these research findings into clinical decision-making, additional studies were required to evaluate the potential therapeutic effects of serum testosterone regulation on the development of heart failure.

One of the strengths of this study was the use of a large representative sample from NHANES, which gave our results a certain degree of generalizability and applicability to non-institutionalized civilian populations. Additionally, we implemented strict participant selection criteria, excluding individuals who were less likely to be associated with lower clinical serum testosterone decline in younger males and those with missing information on serum testosterone and CHF, thus increasing the reliability of the study. However, there were also some limitations to this study. Firstly, due to the cross-sectional design, it was challenging to determine causality. Secondly, the measurement of serum testosterone levels may have been influenced by various factors such as sampling time and laboratory techniques. Although we implemented strict controls during the measurement process, these factors may still have had some impact on the results. Thirdly, the diagnosis of CHF was based on a retrospective medical history questionnaire, which may have been subject to recall bias and information errors. Fourth, due to the relatively small number of individuals with low levels of serum testosterone in the population under 50 years old, we were unable to obtain statistically significant results in this age group. Lastly, the sample for this study primarily consisted of non-institutionalized civilian populations in the United States, which may have limited the generalizability of the results to other countries. For future research, it is recommended to employ longitudinal tracking study designs to determine whether there is a causal relationship between serum testosterone levels and the occurrence of CHF. Furthermore, further investigation into the biological mechanisms between serum testosterone levels and the onset of CHF would be beneficial in enhancing our understanding of their relationship.