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Open Access

Peer-reviewed

Research Article

Association of systemic immune-inflammatory index with stress urinary incontinence in U.S. Adults: NHANES 2007–2016

  • Sijia Ma,

    Roles Conceptualization, Formal analysis, Methodology, Software, Writing – original draft

    Affiliations Department of Nephrology, The Third Affiliated Hospital of Zhejiang Chinese Medical University (Zhongshan Hospital of Zhejiang Province), Hangzhou, Zhejiang, China, Institute of Basic Theory of Traditional Chinese Medicine, China Academy of Chinese Medical Sciences, Beijing, China

    ⨯
  • Linlin Qian,

    Roles Formal analysis, Methodology, Software, Writing – original draft

    Affiliation Department of Nephrology, The Third Affiliated Hospital of Zhejiang Chinese Medical University (Zhongshan Hospital of Zhejiang Province), Hangzhou, Zhejiang, China

    ⨯
  • Yuhua Jiang,

    Roles Formal analysis, Methodology, Writing – original draft

    Affiliation Department of Nephrology, The Third Affiliated Hospital of Zhejiang Chinese Medical University (Zhongshan Hospital of Zhejiang Province), Hangzhou, Zhejiang, China

    ⨯
  • Meng Wang,

    Roles Formal analysis, Software

    Affiliation Department of Nephrology, The Third Affiliated Hospital of Zhejiang Chinese Medical University (Zhongshan Hospital of Zhejiang Province), Hangzhou, Zhejiang, China

    ⨯
  • Shijie Xu ,

    Roles Supervision, Writing – review & editing

    xushijie6666@sohu.com (SX); wangchao19891216@163.com (CW)

    Affiliation Department of Nephrology, The Third Affiliated Hospital of Zhejiang Chinese Medical University (Zhongshan Hospital of Zhejiang Province), Hangzhou, Zhejiang, China

    ⨯
  • Chao Wang

    Roles Conceptualization, Supervision, Writing – review & editing

    xushijie6666@sohu.com (SX); wangchao19891216@163.com (CW)

    Affiliation Department of Nephrology, The Third Affiliated Hospital of Zhejiang Chinese Medical University (Zhongshan Hospital of Zhejiang Province), Hangzhou, Zhejiang, China

    ⨯

Abstract

Background

The aim of this study is to explore the association between the systemic immune-inflammatory index (SII) and stress urinary incontinence (SUI).

Methods

We used information obtained from the National Health and Nutrition Examination Survey (NHANES) that was conducted between 2007 and 2016. The weighted multivariate logistic regression model was used in order to evaluate the relationship that exists between the SII index and the SUI measurement. In addition, a technique from the field of smooth curve fitting was used to investigate the linear connection that exists between these variables. In order to determine whether or not the SII index and SUI relationship remained stable across a variety of demographic strata, subgroup analyses were carried out.

Results

The research had a grand total of 20,849 individuals. After full adjustment for confounders, each 1-unit increase in log₁₀(SII) was associated with a 29.7% increase in the odds of SUI (OR=1.297, 95%CI 1.028–1.636, P = 0.032). Categorizing the SII index into quartiles revealed that even in the highest SII quartile, there remained a significant positive association with SUI when compared to the lowest quartile (OR =1.177, 95%CI 1.013–1.368, P = 0.038). Furthermore, an augmented correlation between alcohol consumption and SUI was detected among drinkers compared to non-drinkers (P < 0.05).

Conclusions

Higher systemic inflammatory burden reflected by SII is statistically significantly associated with increased odds of SUI in the U.S. adult population, though the effect size is small; this association is particularly prominent in alcohol drinkers.

Citation: Ma S, Qian L, Jiang Y, Wang M, Xu S, Wang C (2026) Association of systemic immune-inflammatory index with stress urinary incontinence in U.S. Adults: NHANES 2007–2016. PLoS One 21(7): e0353080. https://doi.org/10.1371/journal.pone.0353080

Editor: Qian Wu, The First Affiliated Hospital of Soochow University, CHINA

Received: August 14, 2024; Accepted: June 18, 2026; Published: July 9, 2026

Copyright: © 2026 Ma et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Data Availability: The datasets generated and analysed during the current study are available in the NHANES database repository, https://www.cdc.gov/nchs/nhanes/index.htm.

Funding: This work was funded by the Scientific and technological innovation project China Academy of Chinese Medical Science (Grant No. CI2021B001); the Fundamental Research Funds for the Central Public Welfare Research Institutes (Grant No. YZX - 202409); and the Fundamental Research Funds for the Central Public Welfare Research Institutes (Approval No. YZX - 202345).The funders provided research funding, including reimbursement of the manuscript’s publication fee; The funders provided research facilities and venues, which supported the research team in conducting systematic training on the NHANES database and completing data collection. The funders had no role in study design, data analysis, decision to publish, or preparation of the manuscript.

Competing interests: The authors have declared that no competing interests exist.

Introduction

Urinary incontinence (UI) is a common condition affecting a large portion of the population, often leading to significant decline in patients’ quality of life and social participation. It imposes a considerable psychological burden on affected individuals and increases social and economic pressures [1].

Stress urinary incontinence (SUI) is the most prevalent subtype of UI, characterized by involuntary urine leakage triggered by activities that increase intra-abdominal pressure (e.g., sneezing, coughing, laughing, or physical exertion), resulting from impaired urethral continence mechanisms [2]. According to statistical data, SUI significantly impacts 10% ~ 40% of women [3]. Additionally, during 2017–2020, over one-third of men aged 60 years and older reported experiencing any form of urinary incontinence, with urgent urinary incontinence being the most common (31.3%) [4]. Currently, the management of SUI mainly includes lifestyle modifications, physical therapy, pharmacological interventions, and surgical approaches. These modalities aim to alleviate symptoms and enhance the quality of life for affected individuals to varying degrees [5].

The systemic immune inflammation index (SII), calculated by multiplying platelet count by neutrophil-to-lymphocyte ratio, has been recognized as predictive of inflammatory status in humans [6]. Elevated SII typically reflects increased chronic inflammation and has been identified as a prognostic marker for various diseases, including cancer, cerebral hemorrhage, and coronary artery stenosis [7–9]. Chronic inflammation is also associated with degenerative changes in the pelvic floor support structures (e.g., muscles, fascia, ligaments), which may compromise their supportive capacity [10]. However, the relationship between SII and SUI remains unclear.

To address this research gap, our study used a nationally representative sample of U.S. adults aged ≥20 years to explore the association between SII and SUI. Early identification, diagnosis and intervention may help reduce the incidence of SUI and its complications, as well as alleviate patient distress.

Methods

Study population

NHANES is a nationally representative survey designed to assess the health status of the U.S. population. Over two decades, this program has collected data on demographics, examinations, nutrition, and laboratory findings. NHANES employs a complex, multi-stage stratified random sampling method to ensure the sample is representative of non-institutionalized U.S. citizens. All participants provided written informed consent. For detailed study protocols, refer to the official website (https://www.cdc.gov/nchs/nhanes).

In this study, we analyzed data from five NHANES survey cycles (2007–2016). Initially, 50,588 participants were included. We excluded individuals with missing SII data (n = 8974), missing SUI data (n = 17417), pregnant participants (n = 250), and those with missing information on other relevant covariates (n = 3098). Finally, 20,849 participants were included in the analysis (Fig 1).

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Fig 1. Participant selection criteria.

https://doi.org/10.1371/journal.pone.0353080.g001

Assessment of stress urinary incontinence

SUI was assessed using a self-reported questionnaire focusing on symptoms occurring in the past 12 months. Participants were asked: “Have you experienced involuntary leakage or loss of even a small amount of urine during activities such as coughing, lifting, or exercising?” [11–13]. A positive response was defined as having SUI.

Assessment of systemic immune-inflammation index

Complete blood counts were performed using a Coulter® DxH 800 analyzer under the guidance of trained medical professionals, with results reported in ×10⁹ cells/µl. The SII was calculated as follows [14,15].

Covariates of interest

Covariates included demographic and lifestyle factors such as gender, age, race/ethnicity, educational attainment, marital status, family poverty-to-income ratio (PIR), body mass index (BMI), waist circumference, smoking habits, alcohol consumption, level of physical activity (vigorous/moderate), as well as the presence of status diabetes, hypertension, and high cholesterol. Smoking status was categorized into three groups: never smoked (lifetime consumption <100 cigarettes), former smokers (lifetime consumption >100 cigarettes but currently not smoking), and current smokers (lifetime consumption ≥100 cigarettes and currently smoking) [12,13]. Diabetes status was categorized as yes, no, or borderline.

Statistical analysis

To account for NHANES’ complex multi-stage sampling design, we incorporated sample weights, SDMVPSU (SDMV Primary Sampling Unit), and SDMVSTRA (stratification) into statistical analyses to ensure representativeness of the non-institutionalized U.S. civilian population. Continuous data were presented as weighted means ± standard errors (SE), and categorical variables as weighted proportions. Baseline characteristics across SII quartiles were compared using survey-weighted chi-square tests (categorical variables) and survey-weighted linear regression (continuous variables).

Subgroup analysis was performed to explore the stability of the SII-SUI association across different strata. Smooth curve fitting was used to evaluate the nonlinear relationship between SII and SUI, and a threshold effect analysis model was employed to identify potential inflection points. The two-sided P-value of less than 0.05 was used to evaluate statistical significance. R 4.2.2 and EmpowerStats 4.2 were the software programs used for the statistical studies.

Results

Participant characteristics

The study included 20,849 participants (10,222 men and 10,627 women) with a mean age of 51.44 ± 17.35 years. The prevalence of SUI in the cohort was 23.67%. After log₁₀ transformation, the SII quartiles were: Q1 (0.18 ~ 2.51), Q2 (2.51 ~ 2.66), Q3 (2.66 ~ 2.81), and Q4 (2.81 ~ 4.45). Compared with participants in the lowest SII quartile (Q1), those in the highest quartile (Q4) were older, more likely to be non-Hispanic white women, had lower household income and educational attainment, and higher rates of living alone, smoking, elevated BMI and waist circumference, hypertension, hyperlipidemia, diabetes, and SUI (all P < 0.001; Table 1).

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Table 1. Baseline characteristics of participants by the SII index quartiles, weighted.

https://doi.org/10.1371/journal.pone.0353080.t001

Relationship between SII index and SUI

Weighted multivariate logistic regression models were used to assess the association between SII index and SUI under three adjustment scenarios: crude (Model 1), minimally adjusted (Model 2), and fully adjusted (Model 3). Results showed a positive correlation between elevated SII and increased SUI risk.

When SII was treated as a continuous variable, after full adjustment for all covariates (Model 3), each 1-unit increase in log₁₀(SII) was associated with a significant increase in the odds of SUI (OR=1.297, 95% CI 1.028–1.636, P = 0.032). In the highest SII quartile(Q4), compared with Q1, the SUI risk increased by 17.7% after full adjustment (OR=1.177, 95% CI 1.013–1.368, P < 0.05; Table 2).

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Table 2. Following the adjustment of various covariates, the SII index and the weighted association between SUI.

https://doi.org/10.1371/journal.pone.0353080.t002

Furthermore, smooth curve fitting analysis indicated a linear and positive correlation between the SII index and SUI (Fig 2).

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Fig 2. Smooth curve fitting plot of the association between SII and SUI.

The area between the two blue dashed lines represents the 95% CI. The red dashed line indicates a linear positive correlation between the SII index and SUI.

https://doi.org/10.1371/journal.pone.0353080.g002

Threshold effect analysis

A two-piecewise linear regression model was used to identify the threshold effect between log₁₀SII and SUI (Table 3). The results showed that the prevalence of SUI peaked when log₁₀SII reached 2.604. Below this breakpoint (log₁₀SII < 2.604), there was a significant positive correlation (OR=1.646, 95%CI: 1.152–2.351, P < 0.05). Above the threshold (log₁₀SII > 2.604), the positive correlation persisted but was not statistically significant (OR=1.038, 95%CI: 0.803–1.343, P > 0.05).

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Table 3. The two-piecewise linear regression model analysis between log10SII and SUI threshold effect.

https://doi.org/10.1371/journal.pone.0353080.t003

Subgroup analysis

A subgroup study was conducted to assess the stability of the connection between the SII index and SUI across various levels. The stratification criteria were gender, age, smoking status, diabetes, hypertension, and high cholesterol. Fig 3 demonstrates that alcohol use might potentially affect the relationship between the SII index and SUI. When comparing drinkers to nondrinkers, the SII index showed a stronger association with SUI (P for interaction < 0.05).

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Fig 3. Subgroup analysis of the association between SII index and SUI.

Squares represent OR values (ratio of SUI occurrence between groups), and horizontal lines represent 95% CI.

https://doi.org/10.1371/journal.pone.0353080.g003

Discussion

This study used a large, nationally representative sample from the 2007–2016 NHANES database to evaluate the association between SII and SUI in U.S. adults. Among 20,849 participants, we found that elevated SII was positively associated with SUI. Quartile analysis confirmed a dose-dependent relationship, and smooth curve fitting revealed a linear association (log10SII inflection point: K < 2.604, P < 0.05). Notably, the association was stronger in alcohol consumers, suggesting that lifestyle factors may modify this relationship. This enhanced association may be attributed to several potential pathways: first, alcohol itself exerts pro-inflammatory effects that could amplify systemic inflammatory burden; second, alcohol consumption may be associated with weight gain, increased coughing, or other behaviors that exacerbate urinary leakage; third, alcohol use might serve as a surrogate for unmeasured lifestyle factors (e.g., poor dietary habits) that contribute to both inflammation and SUI. However, we acknowledge that this interaction finding should be interpreted cautiously, given the multiple subgroup tests conducted, which may increase the risk of false positivity.

These findings position the SII—a well-validated marker of systemic inflammation [9,10,16–18]—as a promising predictor for SUI risk, highlighting its potential value in clinical assessment. SUI is a prevalent condition that significantly impacts patients’ psychological health and societal functioning [19]. Its primary pathological mechanisms include impaired neural control dysfunction of urinary tract structures, compromised pelvic floor support, and dysfunctional urethral sphincter, leading to inability to maintain urethral closure during increased intra-abdominal pressure [20,21]. Gender-specific risk factors exist: in women, pregnancy and vaginal delivery can cause urethral sphincter injury; in men, SUI often results from neurovascular bundle and fascia trauma during radical prostatectomy [22–24]. Additional risk factors such as smoking, obesity, and constipation further exacerbate the condition [25,26]. SUI is also associated with comorbidities including sleep disturbances, depression, insulin resistance, and urinary tract infections [27–30]. Despite these well-documented risk factors and mechanisms, the relationship between SII and SUI remains unexplored. Given the potential mediating role of chronic inflammation in pelvic floor dysfunction, the present study focuses on the value of SII as a novel predictive marker for SUI, aiming to provide critical evidence for the early identification, prevention, and clinical management of SUI, thereby filling the existing research gap in this field.

Notably, our results align with emerging evidence linking inflammation to pelvic floor dysfunction (PFD). PFD is a common urological condition encompassing pelvic organ prolapse (POP), SUI, fecal incontinence, and overactive bladder syndrome (OAB) [31]. Recent studies have increasingly implicated immune-inflammatory responses in the pathogenesis of OAB, and several studies have reported a positive correlation between SII levels and OAB [32,33].

The mechanistic plausibility of this association is supported by prior research. A systematic review of molecular processes in SUI (in humans and animals) found that SUI is related to changes in extracellular matrix metabolism, apoptosis, and inflammation [34]. Animal studies have shown lower expression of smooth muscle alpha-2 actin (ACTa2) in SUI models compared to controls [35], while human studies reported decreased transforming growth factor-beta 1 (TGF-β1) protein levels in SUI patients [36]. Another animal study showed increased protein expression of TNF-α, Interleukin-1 (IL-1) in the SUI model compared to controls [37]. A serum proteomic analysis of SUI patients (n = 19) and healthy controls (n = 19) identified 33 proteins associated with inflammatory responses, coagulation reactions, cellular stress, and cytoskeletal stability/mobility in SUI samples [38].

Several mechanisms may explain the positive correlation between SII and SUI. As previously reported, elevated SII is associated with increased levels of inflammatory markers such as C-reactive protein (CRP), TNF-α, and IL-6 [39,40]. Inflammation plays a significant role in SUI pathogenesis by damaging pelvic floor support structures and impairing urethral sphincter function [41–43]. Research indicates that inflammation can lead to structural and functional abnormalities in pelvic floor tissues, including alterations in muscle contraction strength and neural regulation, thereby increasing the risk of urinary incontinence [44,45]. Additionally, inflammatory processes may be associated with mucosal inflammation of the urethra and bladder, which could affect urine storage and voiding, potentially worsening SUI symptoms [46,47]. Moreover, allergies, urinary tract infections, and gynecological inflammation have been shown to worsen SUI symptoms [48,49]. Collectively, these findings suggest that SII may serve as a potential therapeutic target for SUI.

This study aimed to determine the association between SII and SUI in U.S. adults. Rigorous sampling design and weighting methods were used to ensure statistical analyses accurately reflected the demographics of the U.S. adult population. Nevertheless, several limitations warrant acknowledgment.

Primarily, our study adopted a cross-sectional design, precluding the exploration of a causal relationship between the SII index and SUI. Additionally, constraints inherent to the SUI questionnaire design within the NHANES database necessitated reliance on participant self-reports regarding symptoms and medical history, potentially resulting in an underestimation of SUI prevalence. This reliance on self-reporting mechanisms introduces variability influenced by participants’ interpretation of questions and varying educational backgrounds, thereby heightening concerns regarding recall bias and misclassification bias, particularly concerning the accurate differentiation between Urge Urinary Incontinence (UUI) and SUI. Furthermore, it’s imperative to acknowledge that the NHANES database exclusively encompasses data from the U.S. population. Consequently, future research endeavors should encompass prospective studies incorporating sizable cohorts from diverse global regions to validate the observed association between the SII index and SUI across different national demographics.

Conclusion

To our knowledge, this study represents the inaugural examination of the correlation between the SII index and SUI within the US adult demographic. We found a statistically significant positive correlation, with higher SII index values linked to an increased risk of SUI, consistent across SII quartiles. Elevated SII may increase the risk of SUI by impairing pelvic floor structure and function through multiple mechanisms, including chronic inflammation, oxidative stress, metabolic disorders, and vascular dysfunction. These findings underscore the significant association between SUI and SII, highlighting the potential role of SII in urinary dysfunction. We thus advocate for clinicians to incorporate inflammatory evaluation into the comprehensive management of patients with urinary symptoms. Nonetheless, further investigations conducted on a global scale are imperative to corroborate and extend the generalizability of our observed associations.

Acknowledgments

We extend our sincere appreciation to the NHANES database.

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