Association between inflammatory burden index and erectile dysfunction: a retrospective case–control study

Abstract

Background

Erectile dysfunction (ED) is a vascular disease associated with systemic inflammation and endothelial dysfunction. The role of inflammatory markers in the pathogenesis of ED is gaining increasing importance. This study aimed to evaluate the relationship between the Inflammatory Burden Index (IBI), calculated by combining C-reactive protein (CRP) and neutrophil-lymphocyte ratio (NLR), and erectile dysfunction.

Methods

This retrospective study included 126 patients with erectile dysfunction and 128 healthy controls who presented to the urology outpatient clinic between January 2023 and October 2025. Erectile function was assessed using the International Index of Erectile Function-5 (IIEF-5). NLR was calculated as the ratio of absolute neutrophil count to absolute lymphocyte count, and IBI was obtained using the formula CRP × NLR. Diagnostic performance was examined using ROC analysis. Multivariate logistic regression analysis was performed to identify independent risk factors for erectile dysfunction.

Results

IBI values were found to be significantly higher in the ED group compared to the control group (median 3.31 vs. 0.91, p < 0.001). No significant difference was found between the groups in terms of NLR. There was no significant difference in IBI values between the ED severity groups (p = 0.346). ROC analysis showed modest discriminatory ability of IBI for ED (AUC = 0.754; 95% CI: 0.696–0.813; p < 0.001). Based on the Youden index, the optimal cutoff value was 3.785, with sensitivity 43.7% and specificity 84.3% (Youden index = 0.280). Additionally, a weak positive correlation was found between IBI and body mass index (r = 0.197; p = 0.027). In multivariate logistic regression analysis, diabetes mellitus and cardiovascular disease were identified as independent predictors of erectile dysfunction, while IBI was not found to be an independent predictor.

Conclusions

IBI levels were significantly higher in patients with erectile dysfunction and may reflect systemic inflammatory burden associated with ED. However, because IBI was not an independent predictor in multivariable analysis and its discriminatory performance remained modest, its clinical utility as a standalone diagnostic or screening marker appears limited.

Introduction

Erectile dysfunction (ED) is defined as the inability to achieve or maintain an erection sufficient for satisfactory sexual performance [1]. ED is a common male health problem that can occur in all age groups and significantly affects the quality of life of both patients and their partners. More than 150 million men worldwide have ED [2]. Prevalence increases with age; 2–9% between the ages of 40–49, 20–40% between the ages of 60–69, and around 50% over the age of 70 [3].

Erectile dysfunction is caused by the interaction of vascular, neurological, and hormonal mechanisms. Tobacco use, obesity, sedentary lifestyle, and chronic alcohol consumption are major risk factors. In addition, comorbid conditions such as diabetes, hypertension, dyslipidemia, and depression increase the risk of developing ED [4, 5]. Currently, endothelial dysfunction is considered a common end pathway in the pathogenesis of ED. ED can be an early sign of widespread endothelial dysfunction and a predictor of other types of cardiovascular disease [6].

In recent years, there has been increasing evidence that inflammation plays a central role in the development of ED. The presence and severity of ED have been shown to be associated with inflammatory markers. The neutrophil-lymphocyte ratio (NLR) is considered an easily accessible and prognostic biomarker of systemic inflammation [7]. In addition, parameters such as the monocyte-lymphocyte ratio (MLR), systemic immune-inflammation index (SII), and systemic inflammation response index (SIRI) have also been reported to be associated with ED [8]. More recently, other candidate biomarkers and risk factors related to endothelial and metabolic dysfunction, such as serum adropin, have also been investigated in patients with ED [9]. Likewise, comorbid conditions linked to systemic inflammation and endothelial dysfunction, such as obstructive sleep apnoea, have also been associated with ED [10]. Chronic low-grade inflammation forms an intermediate step in endothelial dysfunction in conditions such as obesity, metabolic syndrome, and diabetes, and contributes to the pathogenesis of ED [11].

The Inflammatory Burden Index (IBI) is a new parameter calculated by combining C-reactive protein (CRP) and NLR, and is thought to reflect the systemic inflammatory burden more holistically [12]. IBI was initially developed to assess the prognostic value of inflammation and has been found to be associated with clinical outcomes in various diseases [13]. Today, it is used in prognostic studies of cancer and cerebrovascular diseases. IBI can accurately reflect the body’s inflammatory state, better evaluate the effectiveness of treatment, and predict the prognosis of patients [14].

However, studies examining the relationship between IBI and ED are limited in the literature. Therefore, the aim of our study is to evaluate IBI levels in ED patients and to investigate whether IBI is an independent predictor of ED.

Materials and methods

Study design and study population

This retrospective study was conducted after obtaining approval from the Ordu University Clinical Research Ethics Committee (Approval No: 2025/397). Medical records of patients who applied to the Urology Outpatient Clinic of Ordu University between January 2023 and October 2025 were retrospectively reviewed. A total of 254 patients were included in the study. Of these, 126 were patients diagnosed with erectile dysfunction (ED), and 128 were healthy control individuals without erectile dysfunction. Demographic characteristics, clinical data, and laboratory parameters of all participants were recorded. The control group consisted of individuals without erectile dysfunction who attended the same outpatient clinic during the study period, and the absence of ED was confirmed using the IIEF-5 questionnaire.

Inclusion criteria

• Being 20 years of age or older.

• Having an active sexual life.

• Having complete clinical and laboratory data.

Exclusion criteria

• Presence of chronic inflammatory disease

• History of malignancy

• History of pelvic or penile surgery

• History of pelvic trauma

• Neurological diseases

• Severe hepatic or renal insufficiency

• Use of erectile dysfunction treatment

• Genital anatomical abnormalities

Clinical evaluation

The International Index of Erectile Function-5 (IIEF-5) questionnaire [15], which has been validated and proven reliable in Turkish, was used for the evaluation of erectile function.

According to IIEF-5 scores, the severity of erectile dysfunction was classified as follows:

• 22–25: No ED

• 17–21: Mild ED

• 12–16: Mild-moderate ED

• 8–11: Moderate ED

• 5–7: Severe ED [16]

Individuals with IIEF-5 scores of 22–25 were classified as having no ED and were included in the control group.

Clinical characteristics of the participants, such as age, body mass index (BMI), smoking, diabetes, hypertension, history of cardiovascular disease, presence of psychological and neurological diseases, were recorded. Body mass index was calculated by dividing body weight in kilograms by the square of height in meters (kg/m²).

Laboratory analysis

All laboratory parameters were recorded retrospectively from the hospital information system.

The laboratory parameters evaluated were:

• Complete blood count

• C-reactive protein (CRP)

• Fasting blood glucose

• Lipid profile

Neutrophil-lymphocyte ratio (NLR) was calculated by dividing the absolute neutrophil count by the absolute lymphocyte count. The Inflammatory Burden Index (IBI) was calculated using the following formula [17]:

Statistical analysis

Statistical analyses were performed using IBM SPSS Statistics version 26.0 (IBM Corp., Armonk, NY, USA). Continuous variables were expressed as mean ± standard deviation or median (minimum–maximum) according to their distribution characteristics. Categorical variables were presented as numbers and percentages.

The Mann–Whitney U test was used for comparisons between erectile dysfunction and control groups. The Kruskal–Wallis test was applied to evaluate the differences between ED severity groups.

To evaluate the diagnostic performance of IBI in predicting erectile dysfunction, Receiver Operating Characteristic (ROC) curve analysis was performed and the area under the curve (AUC) and 95% confidence interval were calculated. The relationships between IBI and clinical variables were evaluated with Spearman correlation analysis. Multivariate binary logistic regression analysis was performed to identify independent risk factors for erectile dysfunction. Variables included in the multivariable model were selected based on univariable statistical significance and clinical relevance according to the literature. Age, body mass index, smoking, diabetes mellitus, hypertension, history of cardiovascular disease, and IBI were entered into the model. Multicollinearity among covariates was assessed using variance inflation factor (VIF) and tolerance values before model construction. No significant multicollinearity was detected, as all tolerance values were > 0.20 and all VIF values were < 5. Results are reported as odds ratios (ORs) with 95% confidence intervals (CIs).

A p-value < 0.05 was considered statistically significant in all analyses.

Results

A total of 254 participants were included in this study. Of these, 126 were patients diagnosed with erectile dysfunction (ED), and 128 constituted a healthy control group. The control group consisted of individuals without ED, as confirmed by IIEF-5 assessment.

The age of the ED group was 53.5 (25–74), and the age of the control group was 57.5 (39–77). No significant difference was observed between the two groups in terms of body mass index (BMI) (p > 0.05). No significant differences were observed in terms of relationship status, alcohol use, and smoking (p > 0.05) (Table 1).

Table 1.

Demographic and clinical characteristics of the study population

Variables	ED (n = 126)	Control (n = 128)	p
Age, years	53.5 (25–74)	57.5 (39–77)	0.001
BMI, kg/m²	28.57 (20.28–39.10)	28.30 (20.31–41.87)	0.365
Relationship status	121 (96.0%)	127 (99.2%)	0.095
Alcohol use	14 (11.1%)	8 (6.3%)	0.259
Smoking	60 (47.6%)	49 (38.3%)	0.231
Smoking pack-years	22 (1–100)	20 (2.5–40)	0.056
Diabetes mellitus	32 (25.4%)	19 (14.8%)	0.051
Hypertension	45 (35.7%)	33 (25.8%)	0.087
Cardiovascular disease	30 (23.8%)	21 (16.4%)	0.142

Data are presented as median (min–max) for continuous variables and n (%) for categorical variables

BMI Body mass index

When comorbid diseases were examined, diabetes, hypertension, and a history of cardiovascular disease were found to be numerically higher in the patient group; however, no statistically significant difference was found between the groups in terms of these variables (p > 0.05) (Table 1).

In laboratory parameters, CRP levels were found to be significantly higher in the ED group compared to the control group (p < 0.001). Furthermore, HDL-C levels were found to be higher in the control group (p = 0.032), while platelet (PLT) count was significantly higher in the ED group (p = 0.014). No significant differences were observed between the groups in terms of other biochemical and hematological parameters (p > 0.05) (Table 2).

Table 2.

Laboratory Parameters in ED and Control Groups

Variables	ED [median (min–max)]	Control [median (min–max)]	p
Fasting glucose (mg/dL)	102.00 (79.00–307.00)	104.00 (81.90–279.00)	0.825
Total cholesterol (mg/dL)	191.00 (114.70–343.00)	194.25 (138.00–304.10)	0.944
Triglyceride (mg/dL)	140.00 (9.66–1346.00)	117.20 (54.20–441.30)	0.058
HDL-C (mg/dL)	42.45 (22.50–98.70)	44.90 (29.90–98.50)	0.032
LDL-C (mg/dL)	114.10 (58.40–217.80)	117.50 (64.72–209.48)	0.496
CRP (mg/L)	1.88 (0.26–15.50)	0.50 (0.02–6.11)	< 0.001
ESR (mm/h)	13.00 (2.00–44.00)	12.00 (4.00–79.00)	0.733
WBC (10^9/L)	7.04 (4.30–13.62)	6.54 (4.15–11.92)	0.088
Neutrophil (10^9/L)	3.83 (1.97–8.80)	3.66 (1.78–8.07)	0.161
Lymphocyte (10^9/L)	2.23 (0.78–19.70)	2.09 (1.00–4.68)	0.106
Platelet (10^9/L)	238.00 (95.00–409.00)	218.00 (102.00–495.00)	0.014
NLR	1.71 (0.26–5.02)	1.72 (0.74–3.95)	0.911

Data are presented as median (min–max). Sample sizes varied across laboratory parameters because of missing data

HDL-C High-density lipoprotein cholesterol, LDL-C Low-density lipoprotein cholesterol, CRP C-reactive protein, ESR Erythrocyte sedimentation rate, WBC White blood cell count, NLR Neutrophil-to-lymphocyte ratio

No significant difference was found between the ED and control groups in terms of neutrophil-lymphocyte ratio (NLR) (ED group: 1.71 (0.26–5.02), control group: 1.72 (0.74–3.95); p = 0.911).

Inflammatory Burden Index (IBI) values were found to be significantly higher in the ED group. The median IBI value was calculated as 3.31 in the patient group and 0.91 in the control group. When IBI values between groups were compared using the Mann-Whitney U test, it was found that the patient group had significantly higher IBI values than the control group (U = 3930, p < 0.001).

ED patients were divided into four subgroups according to their IIEF-5 score and compared in terms of IBI values. Kruskal-Wallis analysis revealed no statistically significant difference in IBI values between ED severity groups (p = 0.346).

ROC analysis was performed to evaluate the discriminatory ability of IBI for erectile dysfunction. The area under the curve (AUC) was 0.754 (95% CI: 0.696–0.813; p < 0.001). Based on the Youden index, the optimal cutoff value for IBI was 3.785, yielding a sensitivity of 43.7% and a specificity of 84.3% (Youden index = 0.280). Higher cutoff values, such as 9.775, provided very high specificity (99.2%) but markedly reduced sensitivity (9.5%) (Table 3; Fig. 1).

Table 3.

Diagnostic performance of inflammatory burden index for erectile dysfunction

Parameter	AUC	SE	95% CI	p	Cut-off	Sensitivity	Specificity	Youden index
IBI	0.754	0.030	0.696–0.813	< 0.001	3.785	43.7%	84.3%	0.280

AUC Area under the curve, SE Standard error, CI Confidence interval

Fig. 1.

Receiver operating characteristic (ROC) curve analysis of inflammatory burden index for predicting erectile dysfunction (AUC = 0.754, 95% CI: 0.696–0.813)

No significant association was found between IBI and age, smoking, pack-years of smoking, cholesterol levels, diabetes, hypertension, and cardiovascular disease (p > 0.05). However, a weak positive correlation was observed between IBI and BMI (r = 0.197; p = 0.027).

A multivariate binary logistic regression analysis was performed to identify independent risk factors for erectile dysfunction. The regression model included age, body mass index (BMI), smoking, diabetes mellitus, hypertension, history of cardiovascular disease, and Inflammatory Burden Index (IBI). The established regression model was found to be statistically significant (Omnibus χ² = 39.789; p < 0.001). When the model fit was evaluated with the Hosmer–Lemeshow test, it was found to have a good fit (p > 0.05). No significant multicollinearity was observed among the covariates included in the model, as all tolerance values were > 0.20 and all VIF values were < 5. The explanatory power of the model was evaluated using the Nagelkerke R² value, and it was found that the model explained approximately 29% of the variance in erectile dysfunction (Nagelkerke R² = 0.294). Multivariate analysis revealed that diabetes mellitus (OR = 9.871; 95% CI: 1.168–83.388; p = 0.035) and a history of cardiovascular disease (OR = 8.907; 95% CI: 1.062–74.719; p = 0.044) were independent predictors of erectile dysfunction. In contrast, the Inflammatory Burden Index (IBI) was not found to be an independent predictor of erectile dysfunction in the multivariate model (OR = 0.931; 95% CI: 0.821–1.055; p = 0.263) (Table 4).

Table 4.

Multivariable logistic regression analysis for predictors of erectile dysfunction

Variables	OR	95% CI	p
Age	1.016	0.974–1.060	0.465
BMI	0.958	0.778–1.180	0.689
Smoking	1.860	0.862–4.016	0.114
Diabetes mellitus	9.871	1.168–83.388	0.035
Hypertension	2.476	0.844–7.264	0.099
Cardiovascular disease	8.907	1.062–74.719	0.044
IBI	0.931	0.821–1.055	0.263

BMI Body mass index, IBI Inflammatory Burden Index

Discussion

This study evaluated the relationship between erectile dysfunction and the Inflammatory Burden Index (IBI), which reflects systemic inflammatory burden, and showed that IBI levels were significantly higher in ED patients compared to healthy individuals. These findings support the role of systemic inflammation in the pathogenesis of ED.

Systemic inflammation is one of the key determinants of endothelial dysfunction. Increased neutrophils and decreased lymphocytes have been associated with the development of ED [18, 19]. Atherosclerosis impairs erectile function by reducing blood flow in the penile vascular bed. Inflammation plays a critical role in initiating and progressing the atherosclerotic process. The onset and worsening of endothelial dysfunction are associated with increased levels of inflammatory markers and mediators, including CRP, interleukin (IL) 1β, and IL-6 [20]. Increased levels of inflammatory mediators such as CRP, IL-1β, and IL-6 can lead to impaired endothelial function and decreased nitric oxide bioavailability [21]. High CRP levels in ED patients have been shown to be associated with the development and severity of ED [22]. In addition, experimental evidence suggests that targeting inflammatory pathways may improve erectile function; for example, inhibition of inducible nitric oxide synthase has been shown to ameliorate erectile dysfunction in a rat model of type 1 diabetes [23].

The small diameter of penile arteries (1–2 mm) can lead to early manifestation of ED in vascular pathologies [24]. Therefore, ED is often considered one of the early clinical indicators of systemic vascular diseases.

Zhong L. et al. showed that individuals with ED have significantly higher systemic immune-inflammatory index (SII) levels compared to those without ED, and that high SII levels are an independent risk factor for ED [25]. Bank A. et al. demonstrated that the severity of penile vascular disease, as measured by penile Doppler ultrasound, is associated with progressively increasing CRP levels in men with ED [26]. Similarly, Feng X. et al. found a significant association between high NLR levels and ED prevalence [7].

NLR is a commonly used, readily available, and cost-effective biomarker for assessing systemic inflammation [27]. NLR is calculated as the ratio of neutrophil and lymphocyte counts and can provide information about the body’s inflammatory response [28]. Zhang Y. et al. showed that high neutrophil counts and low lymphocyte counts are significantly associated with a higher ED prevalence [21]. However, in our study, no significant difference was found between patient and control groups in terms of NLR values. This finding suggests that a single inflammatory parameter may not adequately reflect the complex inflammatory process in ED pathogenesis.

IBI is an index calculated using a combination of CRP and NLR, aiming to assess systemic inflammatory burden more comprehensively. It is thought that combined inflammatory indices may be stronger markers in vascular diseases [29]. Wang J et al. reported that although IBI has some limitations in terms of clinical use in ED patients, its discriminative performance is high [30].

When the relationship between ED severity and IBI was evaluated, no significant difference was found in IBI values among the ED subgroups created according to the IIEF-5 classification. This finding suggests that inflammatory burden may be more related to the presence of ED than to the severity of the disease.

The ROC analysis yielded an AUC of 0.754, suggesting modest discriminatory ability of IBI for distinguishing ED. Based on the Youden index, a cutoff of 3.785 provided the most balanced sensitivity–specificity profile (43.7% and 84.3%, respectively). In contrast, higher cutoff values such as 9.775 achieved very high specificity at the expense of markedly reduced sensitivity. These findings suggest that although IBI may have some discriminatory value, its performance remains insufficient for use as a standalone diagnostic or screening tool.

No significant correlation was found between IBI and various clinical variables, including age, smoking status, diabetes, hypertension, and cardiovascular disease. This observation suggests that the relationship between IBI and ED is not solely driven by these common comorbidities. The relationship between obesity and chronic inflammation is well-known [31]. Our correlation analysis also found a weak positive association between IBI and BMI, indicating a similar finding to previous studies. Interestingly, the control group was significantly older than the ED group, despite the well-established increase in ED prevalence with advancing age. This unexpected finding may reflect the retrospective design of the study and the selection of controls from the outpatient clinic population rather than from an age-matched community-based cohort. Therefore, selection bias cannot be excluded, and this imbalance should be considered when interpreting the association between IBI and ED.

In the multivariate logistic regression analysis, diabetes and cardiovascular disease were identified as independent predictors of erectile dysfunction. However, IBI was not found to be an independent predictor in the multivariate model. This suggests that IBI may reflect inflammatory processes associated with erectile dysfunction, but this relationship can be partially explained by the influence of certain systemic comorbid conditions.

These findings suggest that IBI may reflect systemic inflammatory burden associated with erectile dysfunction. Nevertheless, given its lack of independent association in multivariable analysis, IBI should be interpreted cautiously and cannot currently be recommended for routine clinical use.

Limitations

This study has several limitations. First, the retrospective design does not allow causal inference. Second, the study was conducted at a single center with a relatively limited sample size, which may reduce generalizability. Third, the control group was significantly older than the ED group, which may indicate selection bias and should be considered when interpreting the findings. In addition, because controls were selected from an outpatient population rather than an age-matched community-based cohort, the possibility of residual confounding cannot be excluded. These limitations suggest that the present findings should be interpreted cautiously and require confirmation in larger prospective multicenter studies.

Conclusion

The results of this study show that IBI levels are significantly higher in patients with erectile dysfunction than in healthy controls, suggesting a possible association between systemic inflammatory burden and ED. However, because IBI was not an independent predictor in multivariable analysis and its discriminatory performance remained modest, its current clinical applicability remains limited. Larger prospective multicenter studies are needed to clarify its potential role.

Abbreviations

ED

Erectile Dysfunction

IBI

Inflammatory Burden Index

CRP

C-reactive Protein

NLR

Neutrophil-to-Lymphocyte Ratio

IIEF-5

International Index of Erectile Function-5

ROC

Receiver Operating Characteristic

AUC

Area Under the Curve

CI

Confidence Interval

OR

Odds Ratio

BMI

Body Mass Index

Authors’ contributions

A.A. conceived and designed the study. A.A., A.Y., and F.S. contributed to data collection. A.A., E.B., and A.Y. performed statistical analysis. A.A. drafted the manuscript. A.A. critically revised the manuscript. All authors reviewed and approved the final manuscript.

Funding

This study received no external funding.

Data availability

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Declarations

Ethics approval and consent to participate

This study was approved by the Ordu University Clinical Research Ethics Committee (Approval No: 2025/397). The study was conducted in accordance with the Declaration of Helsinki. Informed consent was obtained from all participants.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.