Non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio in relation to erectile dysfunction: a cross-sectional study

Abstract

Background

Studies have shown that many diseases can be correctly predicted by the ratio of non-high-density lipoprotein cholesterol (NHDL-C) to serum high-density lipoprotein cholesterol (HDL-C) (NHHR). However, the association between NHHR and erectile dysfunction (ED) risk is unknown. This study looked into the probable link between NHHR and ED occurrence.

Methods

This study made use of data from the National Health and Nutrition Examination Survey (NHANES), which was carried out between 2001 and 2004. The NHDL-C level was divided by the HDL-C level to calculate the NHHR. To look at the connection between ED and NHHR, the researchers employed a range of statistical techniques, such as subgroup analysis, multivariate logistic regression modeling, and smoothed curve fitting.

Results

In the end, 3,961 individuals were enrolled for the study, 2,800 of whom did not have ED, and 1,161 of whom did. NHHR had a strong negative association with ED occurrence. For every unit increase in NHHR, the prevalence of ED fell by 9% in the fully adjusted model. Participants in the highest quartile (Q4) of the NHHR experienced a significantly lower incidence of ED than those in the lowest quartile (Q1). Curve fitting revealed a negative association between NHHR and ED; however, interaction tests and subgroup analysis demonstrated that the substantial relationships between the various subgroups of variables were independent.

Conclusions

Evidence points to a direct correlation between a lower incidence of ED and greater NHHR levels.

Highlight box.

Key findings

• A higher non-high-density lipoprotein cholesterol (HDL-C) to high-density lipoprotein cholesterol ratio (NHHR) is significantly associated with a lower prevalence of erectile dysfunction (ED).

• Each unit increase in NHHR was associated with a 9% decrease in the prevalence of ED in the fully adjusted model.

• Participants in the highest quartile (Q4) of NHHR had a significantly lower incidence of ED compared to those in the lowest quartile (Q1).

• This inverse association remained consistent across various subgroups, including age, body mass index, diabetes status, hypertension, smoking, alcohol use, education level, and poverty-income ratio.

What is known and what is new?

• Dyslipidemia—such as elevated low-density lipoprotein cholesterol (LDL-C) and low HDL-C—has been linked to ED, which is often considered an early marker of cardiovascular disease. NHHR has emerged as a predictive biomarker for various metabolic and cardiovascular conditions.

• This study is the first to identify a significant negative association between NHHR and ED, suggesting that a higher NHHR may be protective against ED. This relationship persisted across multiple subgroups and after adjusting for numerous confounding factors.

What is the implication, and what should change now?

• NHHR may serve as a novel and accessible biomarker to help identify individuals at lower risk of ED, reflecting a more integrated lipid profile than traditional single-parameter measurements.

• Clinicians should consider incorporating NHHR into cardiovascular and metabolic risk assessments, particularly in men presenting with or at risk for ED. However, intentional elevation of LDL-C to raise NHHR is not recommended due to its established cardiovascular risks. Further longitudinal and interventional studies are needed to confirm NHHR’s causal role and clinical utility in ED prevention and management.

Introduction

The most prevalent sexual dysfunction disorder in males is erectile dysfunction (ED), also referred to as impotence. A man’s incapacity to achieve or maintain an erection powerful enough for satisfying sexual activity is the defining feature (1). Research indicates that ED is quite prevalent worldwide and that its incidence rises steadily with age. It is estimated that by 2025, there will be over 300 million ED sufferers worldwide (2). A multitude of variables, including injury, endothelial dysfunction, smooth muscle issues, infection, and oxidative stress, are linked to ED, a complex condition (3). Research has indicated that a number of additional factors, such as aging, smoking, obesity, decreasing testosterone levels, cardiovascular disease (CVD), diabetes, depression, and prostate surgery, are all directly linked to the development of erectile dysfunction (4-6).

According to recent studies, ED is closely linked to the metabolic syndrome (MetS) and its concomitant conditions, which include insulin resistance (IR), hyperglycemia, hyperlipidemia, and chronic inflammation. These elements might be crucial in the emergence of ED (7). Numerous negative consequences, including endothelial dysfunction, decreased heart diastolic function, poor vasorelaxation, decreased coronary blood flow, and increased susceptibility to ischemia, are linked to IR (8). These negative consequences are linked to ED and CVD. Numerous illnesses, including CVD, are frequently brought on by elevated levels of low-density lipoprotein cholesterol (LDL-C) (9). Additionally, having too much or too little LDL-C is a risk factor for ED (10). A growing body of research indicates that lipid metabolic issues may cause testosterone levels to drop, which raises the risk of testosterone shortage and, consequently, ED (11). Furthermore, clinical research has demonstrated a strong correlation between lipid metabolism disorders and testosterone levels, indicating that low levels of high-density lipoprotein cholesterol (HDL-C) and high levels of LDL-C and total cholesterol (TC) are linked to lower testosterone levels, which in turn raises the risk of ED (12). This reciprocal vicious cycle highlights how crucial it is to research how lipid metabolism affects testosterone levels and the risk of ED. Compared to other conventional markers, the non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) has become a more complete measure of lipid metabolism in recent years. It is a better predictor of several disorders, such as metabolic, gynecological, renal, and pulmonary conditions, than HDL cholesterol (13-16). In conclusion, there might be a close connection between NHHR and the onset of ED.

A new complicated lipid marker that is gaining popularity is NHHR. Patients with MetS and high-risk groups benefit significantly from NHHR, which combines the protective lipid component (HDL-C) and the atherogenic lipid component [non-high-density lipoprotein cholesterol (NHDL-C)] into a single ratio that more accurately reflects the balance of atherogenic and anti-atherogenic components. It can also assist researchers in better stratifying cardiovascular risk. It is a significant predictor of death in people with CVD, particularly coronary artery disease, according to numerous studies (17-19). Additionally, because lipid analysis is frequently carried out and the NHHR is derived from the ratio of NHDL-C to HDL-C, it has emerged as a commonly available and reasonably priced indication for assessing the lipid composition of atherosclerosis (20).

As far as we know, limited research has been done on the connection between NHHR and ED in male patients. This is the first instance of a new association between NHHR and ED being found. This could offer insights for preventing or treating ED. This study used data from the U.S. National Health and Nutrition Examination Survey (NHANES) (2001–2004) to investigate on this topic. We present this article in accordance with the STROBE reporting checklist (available at https://tau.amegroups.com/article/view/10.21037/tau-2025-693/rc).

Methods

Survey description for the NHANES

The NHANES, a research program run by the National Center for Health Statistics (NCHS), assesses the overall health and nutritional status of adults and children in the United States. Detailed methods and demographic data are accessible on the official NHANES website (http://www.cdc.gov/nchs/nhanes). The NCHS Institutional Review Board evaluated and approved the survey protocol, and all procedures followed the U.S. Department of Health and Human Services laws for the protection of human research subjects. All subjects provided written informed consent prior to being included in the study. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. Analyzing the nutritional and health status of adults and children is the goal of the NHANES study program in the United States. It differs from other approaches in that it incorporates both a medical examination and an interview. A representative sample for the study was created using stratified multistage probability sampling to accurately assess the nutritional and health conditions of the American people. The public can get detailed information regarding the NHANES investigation.

Study participants

This cross-sectional analysis used data from the 2001 to 2004 NHANES period, which was the only survey to contain questions about ED. Strict inclusion and exclusion criteria were used to include 3,961 persons who were 20 years of age or older in the analysis. There were 21,161 people in the original sample. The remaining 3,961 participants were included after the following exclusion criteria were applied: (I) female (n=10,860); (II) male <20 years (n=5,347); (III) missing ED data (n=838); and (IV) missing NHHR values (n=155). Figure 1 depicts the comprehensive selection procedure, including the specific inclusion and exclusion criteria.

Figure 1.

Flow chart of participant selection. ED, erectile dysfunction; NHANES, National Health and Nutrition Examination Survey; NHHR, non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio.

Assessment of NHHR

Two biomarkers—TC and HDL-C—were used to determine the exposure variables in this investigation. The non-HDL-C value is divided by the HDL-C value when the degree of non-HDL-C is first ascertained, which is done by deducting HDL-C from TC (21). Determine the levels of HDL-C and TC via immunoassay or precipitation methods.

Definition of ED

A systematic questionnaire is used in the KIQ400 assessment of the ED. Interviews were done utilizing the Computer Assisted Audio Self-Interview (CAASI) technique in a private space at the Massachusetts Education Center. ED self-assessment was examined as the dependent variable using a question from the Massachusetts Male Aging Study (MMAS) (22): “How would you describe your ability to get and maintain an erection sufficient for satisfactory sexual intercourse?” The answer alternatives were “never”, “sometimes”, “usually”, and “almost always or nearly always”. Participants who said that they were “sometimes able” or “never able” to maintain an erection were classified as having ED, while respondents who indicated that they were “always or almost always able” or “usually able” to do so were classified as not having ED.

Covariates

Age, race/ethnicity, diabetes, education level, marital status, smoking status, alcohol intake, body mass index (BMI), hypertension, serum uric acid, triglycerides (TGs), serum albumin (ALB), and serum creatinine are some of the possible covariates that may affect the association between NHHR and ED. Ages were classified as <50 and ≥50 years. Mexican American, other Hispanic, non-Hispanic Black, non-Hispanic White, and other race were the categories for race and ethnicity. The normal group’s BMI was less than 25 kg/m², while the overweight/obese group’s was greater than or equal to 25 kg/m². Marital status is divided into “married or living with a partner” and “living alone”. Three poverty-to-income ratio (PIR) classifications were established: PIR <1.3, 1.3≤ PIR <3.5, and PIR ≥3.5. Participants’ alcohol consumption was categorized according to whether they had consumed more than 12 drinks throughout the preceding year. To establish smoking status, participants were asked if they had smoked at least 100 cigarettes in their lifetime and what their current smoking status was. Diabetes and hypertension were utilized in the study as variables for prior medical history. Past medical history was gathered through self-reported personal interviews. There are three categories for educational levels: “below high school”, “high school”, and “above high school”. Additionally, there are test results for serum ALB, serum creatinine, TGs, and uric acid. See the NHANES website (https://www.cdc.gov/nchs/nhanes) for additional information on covariates.

Statistical analysis

The Centers for Disease Control and Prevention (CDC) recommendations were followed for all statistical analyses, and the complex multistage complete cohort survey design was taken into consideration by using the proper NHANES weights. When the NHHR is divided into quartiles, the reference group is placed in the quartile with the lowest value (Q1). Categorical variables are expressed as percentages (%), whereas continuous variables are expressed as mean ± standard deviation (SD). The t-test or Chi-squared test was employed to compare NHHR index quartile subgroups. Multivariate logistic regression was used in three separate models to simultaneously examine if NHHR and ED had a linear connection. A trend test was used to examine the trend of the linear relationship between ED and NHHR (quartiles). Model 1 (unadjusted), Model 2 (adjusted just for race, BMI, smoking status, marital status, age, education level, alcohol intake, and PIR), and Model 3 (adjusted for all variables) were the three models utilized for interaction and subgroup analyses. The possibility of a nonlinear link between NHHR and ED was then investigated using smoothed curve fitting. Additionally, pre-specified effect modifiers were used in this study to evaluate interaction effects. The researchers employed stratification characteristics such as age, education, BMI, diabetes, hypertension, smoking, alcohol usage, and PIR to look for any variations in these particular groups. All statistical analyses were conducted using EmpowerStats (version 2.0) and the survey software package version 4.2.1 R; P<0.05 is considered statistically significant.

Results

Characteristics of participants

Table 1 shows the baseline characteristics of 3,961 patients (mean age 50.11±18.67 years), 1,161 of whom reported suffering from ED. ED patients showed lower NHHR values than healthy controls (P=0.032). The prevalence of ED in the study population was approximately 29.31%. Compared to normal persons, ED patients were significantly older (P<0.0001). In addition to having a lower socioeconomic status, ED patients were more likely to smoke, be solitary, have diabetes and hypertension, and have less education (P<0.001). ED patients were less likely to use alcohol (P=0.005). Additionally, there was a significant difference (P<0.05) in TG, ALB, creatinine, and TC laboratory values between ED patients and non-ED subjects. The two groups had significantly different BMIs (P=0.006).

Table 1. Baseline characteristics of the study participants from NHANES 2001–2004.

Characteristics	Total (n=3,961)	No ED (n=2,800)	ED (n=1,161)	P value
Age (years)	50.11±18.67	43.50±15.73	66.04±15.29	<0.001
BMI (kg/m2)	28.00±5.44	27.85±5.35	28.41±5.64	0.006
PIR	2.80±1.60	2.91±1.62	2.54±1.53	<0.001
TG (mmol/L)	1.78±2.08	1.76±2.15	1.82±1.89	<0.001
ALB (g/dL)	4.33±0.31	4.38±0.30	4.21±0.31	<0.001
Uric acid (mg/dL)	6.08±1.31	6.07±1.25	6.10±1.43	0.94
Creatinine (mmol/L)	92.34±40.06	89.96±38.78	98.07±42.46	<0.001
TC (mg/dL)	199.65±44.49	201.00±44.34	196.39±44.70	0.001
HDL-C (mg/dL)	47.63±13.13	47.61±13.12	47.65±13.17	0.97
NHHR	3.48±1.53	3.52±1.55	3.38±1.47	0.03
Race				<0.001
Mexican American	20.50	20.57	20.33
Other Hispanic	3.51	3.50	3.53
Non-Hispanic White	54.66	52.86	59.00
Non-Hispanic Black	18.28	19.64	14.99
Other races	3.05	3.43	2.15
Education level				<0.001
Less than high school	28.23	23.25	40.14
High school or GED	24.59	26.25	20.59
Above high school	47.21	50.50	39.28
Marital status				<0.001
Married/living with a partner	68.72	33.23	26.53
Living alone	31.28	66.77	73.47
Alcohol intake				0.005
Yes	82.71	83.85	80.10
No	7.29	16.15	19.90
Smoked at least 100 cigarettes				<0.001
Yes	59.68	55.46	69.85
No	40.32	44.54	30.15
Hypertension				<0.001
Yes	31.38	23.04	52.70
No	68.62	76.96	47.30
Diabetes				<0.001
Yes	10.45	5.36	22.74
No	88.11	93.46	75.19
Borderline	1.44	1.18	2.07

Data are presented as mean ± standard deviation or %. ALB, albumin; BMI, body mass index; ED, erectile dysfunction; GED, general educational development; HDL-C, high-density lipoprotein cholesterol; NHHR, non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio; PIR, poverty-to-income ratio; TC, total cholesterol; TG, triglyceride.

Association between NHHR and ED

NHHR and ED have a significant association, as Table 2 illustrates. In the uncorrected Model 1, multivariate logistic regression analysis revealed a significant inverse relationship between NHHR and ED [odds ratio (OR) =0.94; 95% confidence interval (CI): 0.90, 0.99]. In Model 2, this substantial negative association remained even after adjusting for age, race, and PIR, education level, marital status, BMI, alcohol consumption, and smoking status (OR =0.93; 95% CI: 0.87, 0.99). NHHR and ED continued to have a negative correlation in fully adjusted Model 3 (OR =0.91; 95% CI: 0.84, 0.99). In particular, the likelihood of ED dropped by 9% for each unit rise in NHHR. When NHHR was converted to quartiles, the negative relationship remained (all P for trend <0.05). As the NHHR interquartile range rose, the protective effect on ED grew stronger in all three models, and this trend was statistically significant (P<0.001). Figure 2 shows a convincing linear relationship between NHHR and ED, utilizing a smooth curve fit, adding weight to the results presented in Table 2.

Table 2. Association between NHHR and ED in logistic regression analysis.

Quartiles of NHHR levels	Model 1			Model 2			Model 3
	OR (95% CI)	P		OR (95% CI)	P		OR (95% CI)	P
NHHR
Continuous	0.94 (0.90, 0.99)	0.01		0.93 (0.87, 0.99)	0.02		0.91 (0.84, 0.99)	0.02
Q1 (0.46–2.38)	Reference			Reference			Reference
Q2 (2.39–3.28)	1.01 (0.84, 1.23)	0.88		0.81 (0.62, 1.05)	0.11		0.82 (0.63, 1.08)	0.16
Q3 (3.29–4.30)	1.00 (0.82, 1.21)	0.96		0.82 (0.63, 1.07)	0.14		0.87 (0.66, 1.15)	0.33
Q4 (≥4.31)	0.78 (0.64, 0.95)	0.01		0.71 (0.54, 0.92)	0.01		0.71 (0.53, 0.96)	0.02
P for trend	0.93 (0.88, 0.98)	0.01		0.91 (0.84, 0.98)	0.02		0.91 (0.84, 1.00)	0.04

Model 1: no covariates were adjusted. Model 2: adjusted for age, race, PIR, education level, marital status, BMI, smoking status and alcohol intake. Model 3: adjusted for age, race, PIR, education level, marital status, BMI, TG, hypertension, smoking status, alcohol intake, diabetes, creatinine, uric acid, and ALB. ALB, albumin; BMI, body mass index; CI, confidence interval; ED, erectile dysfunction; NHHR, non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio; OR, odds ratio; PIR, poverty-to-income ratio; TG, triglyceride.

Figure 2.

Smooth curve fitting diagram of NHHR and erectile dysfunction in fully adjusted models. The solid red line represents the smooth curve fit between variables. Blue bands represent the 95% confidence interval from the fit. NHHR, non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio.

Subgroup analyses

We conducted subgroup analyses to evaluate the consistency of the association between NHHR and ED prevalence across various demographics (Table 3). BMI, level of hypertension, history of diabetes mellitus, level of education, smoking status, level of alcohol intake, age, and PIR level were used to group the participants. Subgroup analysis across categories, including BMI, history of diabetes mellitus, smoking status, level of hypertension, age, level of alcohol consumption, level of education, and level of PIR, revealed consistent relationships between ED and NHHR (all P for interaction >0.05). There was no statistical interaction between ED and NHHR, despite the fact that the correlation was stronger in people over or equal to 50, smokers, people with less than a high school education, people who drank, people without hypertension or diabetes, and people with a PIR level less than 3.5 and greater than or equal to 1.

Table 3. The association between NHHR and ED by selected subgroups.

Subgroup	OR (95% CI)	P value	P for interaction
Age (years)			0.15
<50	0.96 (0.84, 1.10)	0.57
≥50	0.85 (0.78, 0.93)	<0.001
Smoke			0.79
Yes	0.91 (0.83, 0.99)	0.02
No	0.92 (0.81, 1.05)	0.23
Education level			0.24
Less than high school	0.86 (0.74, 0.98)	0.03
High school or GED	1.02 (0.87, 1.20)	0.78
Above high school	0.93 (0.82, 1.05)	0.25
Drinking			0.24
Yes	0.89 (0.82, 0.97)	0.008
No	1.01 (0.83, 1.23)	0.92
Hypertension			0.36
Yes	0.95 (0.84, 1.07)	0.40
No	0.88 (0.80, 0.98)	0.02
Diabetes			0.87
Yes	0.90 (0.78, 1.05)	0.18
No	0.91 (0.84, 0.99)	0.03
Borderline	0.94 (0.55, 1.63)	0.83
PIR			0.90
<1.3	0.96 (0.83, 1.10)	0.52
≥1.3 and <3.5	0.85 (0.75, 0.97)	0.01
≥3.5	0.98 (0.84, 1.15)	0.82
BMI (kg/m2)			0.40
<25	0.87 (0.73, 1.05)	0.16
≥25	0.95 (0.88, 1.04)	0.29

Age, race, PIR, education level, marital status, BMI, TG, hypertension, smoking status, alcohol intake, diabetes, creatinine, uric acid, and ALB were adjusted. The strata variable was not included in the model when stratifying by itself. ALB, albumin; BMI, body mass index; CI, confidence interval; ED, erectile dysfunction; GED, general educational development; NHHR, non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio; OR, odds ratio; PIR, poverty-to-income ratio; TG, triglyceride.

Discussion

In a recent cross-sectional survey of 3,961 representative individuals, a negative correlation between NHHR and ED prevalence was found. This connection was not significantly influenced by BMI, history of diabetes mellitus, smoking status, hypertension, age, alcohol use, education, or PIR in the current investigation. Furthermore, we discovered a linear relationship between a drop in ED risk and an increase in continuous NHHR. Therefore, there is a potential advantage to using the NHHR to identify patients with ED in clinical practice.

ED has become an early indicator of cardiovascular illness since it may share risk factors with CVD, such as metabolic disease, hypertension, and hyperlipidemia (23,24). Our results support the hypothesis that NHHR is intimately linked to ED, given the correlation between ED, cardiovascular illness, and lipid metabolic abnormalities. Remarkably, a number of studies have discovered that the NHHR is a predictor of numerous illnesses. In one example, a study that was conducted using a cross-sectional design and included over 5,000 participants found that there was a negative link between NHHR and benign prostatic hyperplasia (BPH) episodes (25). Elevated NHHR was associated with lower levels of total testosterone, according to another study that examined the relationship between NHHR and testosterone levels (26). Each of the aforementioned discoveries has the potential to offer arguments in support of the findings of this study. Nevertheless, the impact of NHHR on ED was not further examined in these investigations. Consequently, NHANES offers a singular chance to validate the association between NHHR and ED, serving as a foundation for additional investigation into the impact of dyslipidemia on ED.

Our research revealed a negative correlation between NHHR levels and the likelihood of having ED, which may go against conventional wisdom. LDL-C might be protective in the pathophysiology of ED, according to one theory. However, boosting LDL-C to minimize the risk of getting ED is not recommended, as LDL-C has been associated with a higher risk of CVD (25). The mechanisms that produce this opposite outcome may include the following. Although high-density lipoprotein is commonly regarded as protective against CVD due to its anti-inflammatory and antioxidant properties, recent studies suggest that elevated HDL-C levels may paradoxically increase fracture risk and even exacerbate certain cardiovascular conditions under specific inflammatory states (27,28). However, despite HDL-C traditionally being considered protective for cardiovascular health, one study suggests that high levels of HDL-C may be associated with an increased risk of mortality (29). These intricate relationships underscore the necessity for a nuanced understanding of HDL-C function across diverse pathological processes. Concurrently, in certain metabolic dysfunction-associated steatotic liver disease patients, despite elevated HDL-C levels, the quality of HDL particles may deteriorate, resulting in the loss of their protective effects (30). This suggests that elevated HDL-C levels may not be beneficial for all patients. It reflects that HDL concentration does not always indicate anti-atherosclerotic or anti-inflammatory function (functional HDL may alter with disease states); even with low HDL-C, its function varies significantly between individuals (31). Moreover, chronic inflammation may induce a reversal of the conventional lipid-CVD relationship, often referred to as the “lipid paradox” (32). Mechanistically, proinflammatory cytokines [e.g., interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α)] may drive this association by enhancing hepatic LDL receptor expression and impairing HDL function, while simultaneously reducing circulating atherogenic particles and diminishing anti-inflammatory HDL function (33). Finally, the confounding influence of lipid-lowering therapy and the timing of lipid measurement should be considered in cross-sectional analyses. Individuals with higher baseline non-HDL cholesterol levels are more likely to receive statins, which lower non-HDL levels through inhibition of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase and upregulation of hepatic LDL receptors (34). Consequently, their measured non-HDL levels during NHANES may underestimate their pre-treatment lipid status. At the same time, these patients often have greater underlying cardiometabolic risk or potential drug-related effects on erectile function. This combination could produce an apparent inverse cross-sectional relationship (lower measured non-HDL but higher ED prevalence), reflecting confounding by indication and measurement timing rather than a true protective effect of higher NHHR (35). Collectively, these findings suggest that the relationship between lipid metabolism and erectile dysfunction is multifactorial, shaped by HDL functionality, systemic inflammation, and pharmacologic interventions. Future longitudinal and mechanistic studies are warranted to clarify the causal pathways underlying these associations. We conducted subgroup studies to investigate this association in more detail. The probability of having ED was observed to be adversely correlated with NHHR, primarily in the drinking group, the group without diabetes, and the group without hypertension. This illness may be more common in the non-diabetic and non-hypertensive populations because of their better metabolic and cardiovascular health (36). Meanwhile, Chew et al. (37) found a negative relationship between alcohol consumption and the development of ED. One possible explanation is that moderate alcohol consumption lowers blood glucose, increases insulin sensitivity, and decreases glycemic toxicity, all of which minimize the risk of diabetes complications, including ED (38). As the NHHR increased, the likelihood of erectile dysfunction among drinkers tended to decrease, which may help explain this finding. This suggests that a modest increase in NHHR may help reduce the likelihood of developing ED. Furthermore, the MetS, which includes IR, hyperlipidemia, hypertension, and cardiovascular obesity, is a risk factor for erectile dysfunction (7). Non-alcoholic fatty liver disease (NAFLD), on the other hand, is another obvious indicator of MetS (16). According to a recent study, NHHR and MetS are strongly correlated (OR =1.39) (39). Because hyperinsulinemia stimulates anabolic processes and increases the entry of free fatty acids into the liver, it promotes hepatic fat storage and, ultimately, ED. For this reason, IR, the main cause of MetS, is a characteristic of NAFLD (40-42). HDL-C values in ED patients were not significantly different from those in the general population, according to our study. Crucially, compared to the general population, NHHR levels were noticeably lower in ED patients. There may be a connection between elevated NHHR levels and avoiding the onset of ED.

Study strengths and limitations

There are a number of benefits in this study. First, one of the largest epidemiologic studies carried out in the U.S. is NHANES. The data were collected using strict quality control procedures, and the outcomes are very trustworthy. Furthermore, to reduce the influence of bias on the research, confounding factors were adjusted. Additionally, by using subgroup analyses to account for confounders, the results were further supported. Second, the study’s cross-sectional design limits its ability to show a causal association between NHHR levels and ED prevalence.

However, there are certain restrictions on this study. Additional longitudinal or intervention studies are required to demonstrate causality, as our findings are restricted to relationships. Another important limitation is the temporal nature of the dataset and the method used to assess ED. The data analyzed were obtained from the 2001 to 2004 NHANES cycle, collected approximately two decades ago. Since then, population-level lipid distributions, obesity rates, medication use, and overall metabolic health have changed considerably, which may limit the temporal generalizability of our findings. In addition, ED was assessed by self-report using a single question derived from the MMAS questionnaire. This approach may underestimate the true prevalence of ED and introduce recall bias, as participants may underreport mild or intermittent symptoms. Because such misclassification is likely nondifferential, it may attenuate the observed association rather than inflate it. Nevertheless, these limitations should be considered when interpreting the results. Another limitation is that information on lipid-lowering medication use was not included as a covariate. In the NHANES 2001–2004 dataset, this variable was self-reported and lacked details on drug type, dosage, and treatment duration, with substantial missing data. Furthermore, medication timing did not always coincide with laboratory and questionnaire assessments, making accurate exposure classification difficult. Including this variable could have reduced sample size and introduced additional bias. Therefore, we did not adjust for lipid-lowering therapy in the main analyses. Nonetheless, because statins and related agents can influence both lipid and hormonal pathways, potential residual confounding cannot be fully excluded and should be addressed in future studies with more complete medication data. The possible delay between dyslipidemia and the beginning of ED is another drawback. Because atherosclerotic plaque formation is a long-term process that may develop over years or decades, a single-time lipid profile measurement may not accurately represent chronic lipid exposure. This limitation may reduce the ability to infer causality between NHHR and ED, and future longitudinal studies are warranted to validate this relationship.

Conclusions

In summary, a sizable sample of adult U.S. citizens demonstrated that a higher NHHR was linked to a lower incidence of ED on its own. Contrary to other findings in the literature on the effects of dyslipidemia on ED, the data imply that NHHR may be a promising biomarker for detecting patients with ED. It is crucial to remember that this study’s cross-sectional design restricts our capacity to establish causality and evaluate the NHHR’s long-term therapeutic impact. Even though these results are encouraging, more research is required to validate the NHHR’s predictive validity and clinical usefulness in detecting ED patients, including clinical trials and longitudinal investigations. However, because the data were derived from the 2001 to 2004 NHANES cycle and ED was assessed by self-report, the temporal generalizability of our findings may be limited. Future studies using more recent datasets and objective diagnostic tools are warranted to confirm these associations.

Supplementary

The article’s supplementary files as

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments.