The main source of testosterone, an important class of sex hormones, is the testes in the male reproductive system, and in particular, the interstitial cells within the testes are responsible for synthesizing and releasing this hormone in large quantities. In addition to this, the body’s adrenal glands and ovaries are also involved in the production of testosterone (1). As a result, testosterone levels in men are generally significantly higher than in women and are essential for maintaining male secondary sexual characteristics and fertility (2). Research has revealed that the highest levels of testosterone production in men are during puberty and early adulthood, followed by a gradual decrease with age. After the age of 40, there is an annual decline of 0.4%–2.6%, and by the age of 80, testosterone concentrations may be 20% to 50% lower in comparison to younger ages (3–5). The role of testosterone is not limited to sex characterization and individual growth and development but is also involved the maintenance of a variety of physiological functions (6). In the United States, approximately 20% to 50% of men suffer from testosterone deficiency (TD) (7), a prevalent health problem that not only affects reproductive health and sexual function, but also leads to psychological and physiological disorders, cognitive dysfunction, muscular atrophy, osteoporosis, and related metabolic disorders such as depression (8–11). As a key regulator of men’s health, testosterone modulates a number of biological processes that are critical to men’s health. Reduced or insufficient serum testosterone levels have been associated with an increased risk of several cardiovascular diseases, such as hypertension, stroke, and coronary heart disease (12–14). In addition, TD has a pivotal role in the development of metabolic diseases, which include dyslipidemia, diabetes, and obesity (15, 16). Research suggests that deficient testosterone levels may be correlated with the incidence and seriousness of these metabolic diseases. Amid the increasing worldwide demographic shift towards an older population, the associated problem of lower testosterone levels has gradually attracted widespread public attention. Epidemiological statistics reveal that the average prevalence of TD in males above the age of 50 is approximately 7%, with the incidence increasing significantly with age (17, 18). Therefore, identifying and establishing biomarkers that can accurately predict changes in testosterone levels is of paramount importance for clinical practice, not only to help prevent a range of physical and mental disorders caused by testosterone deficiency but also to have a significant impact on improving the overall life satisfaction of patients.

Current medical research has found that individuals with abnormal lipid metabolism and obesity are often accompanied by lower testosterone levels, which rebound significantly when these metabolic problems are effectively treated. These findings reveal a strong link between testosterone levels and an individual’s metabolic health status (19–22). The plasma atherosclerotic index (AIP) is a new lipid biomarker that signifies the characteristics and severity of abnormal lipid metabolic procession (23). The AIP is strongly associated with atherosclerotic load and cardiovascular events (24–28). The AIP reflects the ratio of triglyceride (TG) to high-density lipoprotein cholesterol (HDL-C) and represents the dimensions of lipoprotein molecules, which indicates the disease-causing potential and distinctive nature of dyslipidemia more effectively than TG or HDL-C levels by themselves (29, 30). Since testosterone levels are associated with metabolic status and obesity, and the AIP reflects the lipid metabolic status of an individual, abnormalities in the AIP may suggest changes in testosterone levels. However, to our knowledge, the predictive value of the AIP in diagnosing testosterone deficiency among adult individuals remains unclear. Our research aimed to explore the correlation between the AIP and the prevalence of testosterone deficiency among US adults based on a nationally representative sample.

Our investigation primarily investigated the relevance between the AIP and the prevalence of TD in adult males using the NHANES database. The research involved in a sample size of 4,115 individuals. Weighted multifactorial logistic regression analysis revealed, after all covariates were controlled, a positive and statistically significant relationship between the prevalence of TD and the AIP in adult males. Furthermore, the RCS curves revealed a non-linear positive correlation between TD and the AIP in adult males. Additionally, the prevalence of TD progressively increased with the increasing AIP quartiles in adult males. The subgroup analyses revealed that the relationship between AIP and TD might be altered because of marital status, CKD, smoking, and alcohol consumption. Future research should also explore the complex interplay between the AIP, testosterone, and comorbid conditions such as chronic kidney disease and diabetes mellitus, where dyslipidemia and endocrine dysfunction may create synergistic detrimental effects on male health outcomes.

The positive correlation of the AIP with the incidence of TD varied among certain subgroups. Different marital statuses may lead to different psychological and physiological stresses that may affect the stability of testosterone levels. It has been revealed that men living with a partner have lower testosterone levels compared to unmarried men (31), a result that leads to an unstably positive synergistic relationship between the atherosclerosis index and testosterone deficiency across marital status. Meanwhile, a broad spectrum of studies has underscored that smoking has an effect on sperm density, viability, vigor, and morphology; seminal plasma zinc concentration; and sperm DNA damage in men, with the sperm DNA fracture index being higher in smoking than in non-smoking groups and sperm DNA fragmentation being increased. This suggests that smoking may affect testosterone synthesis and sperm quality by increasing DNA damage (32). Alcohol consumption may lead to abnormal liver function and affect the metabolism of sex hormone-binding globulin, which in turn affects the bioavailability of testosterone (33). In summary, smoking and alcohol consumption may combine to destabilize the association between AIP and testosterone deficiency by affecting the endocrine system, increasing oxidative stress, and affecting liver function. In addition, changes in renal function directly affect hormone metabolism and excretion, which may influence testosterone levels and lead to unstable outcomes. These findings raise important clinical questions about whether targeted interventions such as dietary modifications, lifestyle changes, or pharmacologic lipid-lowering therapies could serve as adjunct strategies for managing androgen deficiency in metabolic syndrome populations, a hypothesis requiring verification through randomized controlled trials. Similarly, lifestyle interventions that reduce visceral adiposity and insulin resistance could ameliorate both the AIP and testosterone deficiency through shared metabolic pathways. Randomized controlled trials are urgently needed to evaluate whether AIP-lowering strategies serve as adjunct therapies for managing androgen deficiency in high-risk populations, particularly those with metabolic syndrome or CKD.

An array of investigations have revealed that TD is a common condition. It has a significant influence on the quality of life and healthy condition of the patient, as well as a remarkable influence on the psychological wellbeing of individuals. Nevertheless, the underlying pathological processes of TD remain incompletely understood. Although the occurrence of TD in the adults has remained at the same level in recent years, the overall incidence and public health impact of the condition remains quite significant given the rising population size, which may indirectly reflect trends in the development of TD in other countries around the globe. This exacerbates the strain on healthcare systems and increases explicit and implicit medical costs connected to the condition. In addition, TD is connected to a variety of chronic diseases, including cardiovascular and disease kidney disease, further increasing the need for public health interventions. An elevated AIP is a key indicator of lipid metabolite interactions and is associated with the incidence of TD, a relationship that may involve multiple mechanisms. We introduced the AIP, which combines triglyceride to HDL-C ratios, and concluded that it more accurately reflects an individual’s metabolic health status.

Several mechanisms may explain the positive relationship between the incidence of TD and AIP in adults with diabetes. These include several aspects such as dyslipidemia, insulin resistance, inflammatory response, and hepatic lipid metabolism (34–38). Initially, research demonstrated that testosterone significantly contributes to the regulation of lipid metabolism in male individuals. Serum testosterone levels were positively correlated with HDL-C and inversely related to low-density lipoprotein cholesterol (LDL-C), triglycerides, and total cholesterol (39, 40). Correlation studies indicate that higher levels of testosterone in the blood are associated with increased levels of HDL-C, while they are inversely related to the concentrations of low-density lipoprotein cholesterol (LDL-C), triglycerides, and total cholesterol.

This implies that endogenous testosterone may be a favorable factor in maintaining the balance of lipid metabolism in men. When testosterone levels are low, this balance is disrupted, resulting in increased levels of TG and non-HDL-C and decreased levels of HDL-C. This implies that testosterone deficiency may contribute to an elevated AIP by affecting lipid levels, specifically by increasing harmful lipid components (TG and non-HDL-C) and decreasing beneficial lipid components (HDL-C) (41). At the same time, testosterone deficiency results in a compromised increase of HDL-C triggered by its conversion to estradiol by aromatase, which also leads to an increased AIP (42). Furthermore, evidence has demonstrated that retinol-binding protein 4 (RBP4) is crucial for managing insulin resistance. Notably, in a murine model exhibiting diminished testosterone activity, there was a marked increase in RBP4 protein concentrations, potentially linking it to the onset of insulin resistance (43–45). Furthermore, insulin resistance could contribute to the activation of the fatty acid synthesis pathway in adipocytes, which promotes fatty acid synthesis and fat accumulation while inhibiting fatty acid oxidation, leading to dyslipidemia (46), which in turn affects AIP levels. In addition, research has demonstrated a strong correlation between testosterone deficiency and increased levels of inflammatory indicators, including high-sensitivity C-reactive protein, interleukin-6, and tumor necrosis factor-alpha (47). This implies that TD may be associated with increased levels of inflammation in the body, while the AIP is dependent on the logarithm of the ratio of plasma TG to HDL-C, which reflects the size of oxidized LDL particles in serum. Inflammatory factors can affect lipid metabolism (48), particularly by increasing the levels of oxidized low-density lipoprotein (oxLDL), which may lead to elevated AIP levels. Ultimately, testosterone may alter the genetic expression linked to the formation and release of lipoproteins, including the scavenger receptor B1 (SR-B1). Hepatic lipase expression is upregulated in hepatocytes. This enzyme catalyzes the breakdown of phospholipids on HDL-C particles and facilitates the selective uptake of HDL-C via SR-B1, which promotes retrograde cholesterol transport and exerts an antiatherosclerotic effect (49), thus leading to the correlation between an elevated AIP and testosterone deficiency. The biological mechanisms underlying this association warrant further investigation, particularly regarding how altered lipid metabolism may impact cell function, steroidogenic enzyme activity, or androgen receptor signaling through inflammatory or oxidative stress pathways.

According to studies in recent years, the current rate of TD in the global population continues to rise, affecting people’s physical and mental health in various ways. Lipid metabolism is closely associated with TD problems. Our investigation confirms a novel demonstration of a significant relationship between the AIP and the occurrence of TD in adult males, which has significant implications for the diagnosis and treatment of TD. This research exhibits several strengths. Based on the NHANES database, the investigation is primarily a cross-sectional investigation to research the correlation between the AIP and TD in adult males. At the same time, our study is representative because it contains basic data from a large number of respondents in the US. However, it is worth noting that we still have some limitations. First, some of the information in the NHANES database was obtained through self-reporting by the respondents, including disease information. Self-reporting bias could lead to imprecise answers, which may affect the accuracy of the results. Second, this investigation could not establish a direct sequential association between TD and the AIP in adult males, but only inferred a correlation, due to it being a cross-sectional study. Longitudinal studies tracking lipid profiles and hormonal changes over time are needed to establish temporal relationships and clarify potential causal pathways. The diagnosis of testosterone deficiency relied solely on a single serum testosterone measurement without clinical symptom assessment. Diurnal variation in testosterone levels and the absence of symptom data may have introduced misclassification bias. Future studies should incorporate repeated measures, standardized morning blood draws, and validated symptom questionnaires. In conclusion, this study suggests there is a positive significant relationship between the AIP and the risk of TD in adult males.

The research revealed a positive significant relationship between the AIP and TD in American adult males. In adult males, a higher AIP was correlated with a higher occurrence of TD. This finding suggests that lipid metabolism may be an influencing factor for TD. The clinical importance of our research is that assessing the AIP may help identify those at higher risk for TD. Incorporation of the AIP into common clinical assessment could contribute to early detection of TD and direct personalized care strategies.