Stress urinary incontinence (SUI) refers to the unintentional loss of urine triggered by activities that increase intra-abdominal pressure [1]. Due to a shorter urethral length, weaker periurethral support tissues, and factors such as childbirth and postmenopausal hormonal decline, women are more frequently affected by this condition. The reported prevalence of SUI among women varies significantly, ranging from 12% to 46% [2, 3]. It is estimated that annual expenditures related to SUI exceed 7 billion euros in European countries such as the United Kingdom, Spain, and Italy [4]. In South Korea, annual medical costs associated with SUI among women aged 40–50 reach as high as $15–20 million [5]. Unfortunately, many women lack awareness of SUI, often perceiving it as a natural consequence of childbirth and aging rather than a health issue [6]. Koch and colleagues demonstrated that less than 38% of women seek assistance for SUI symptoms [7]. This reluctance significantly impacts their social activities, sexual function, and reproductive health. A comprehensive understanding of SUI risk factors is thus critical for raising public awareness, developing preventive healthcare strategies, and enhancing women’s reproductive health.

Obesity is a major contributor to the onset and progression of SUI. It directly increases abdominal, bladder, and pelvic floor pressure, thereby promoting SUI [8]. Additionally, obesity contributes to the accumulation of lipid droplets intracellularly and extracellularly, elevates free fatty acids, and enhances leptin secretion. This process activates interleukin (IL)-6 and oxidative stress factors while decreasing adiponectin secretion, subsequently inhibiting the repair of damaged vascular endothelium [9]. Consequently, oxidative stress imbalances damage pelvic floor muscles, urethral tissues, and pelvic floor nerve function, elevating the risk of SUI [10]. The lipid accumulation product (LAP), calculated using waist circumference (WC) and plasma triglyceride (TG) levels, is a reliable marker of excessive lipid storage in the body. Initially developed to identify cardiovascular risk in American adults, LAP has been strongly correlated with cardiovascular diseases [11].

However, there is limited research examining the relationship between LAP and female SUI, particularly regarding the mediating roles of oxidative stress and inflammatory factors. This study primarily investigates the relationship between LAP and SUI prevalence among women using large-scale population data from a United States public database. Moreover, it evaluates the potential mediating effects of oxidative stress and inflammatory factors, providing additional insights into the role of LAP in the pathogenesis of SUI in women.

In this study, we conducted a retrospective analysis of data from 4,292 adult American women derived from the NHANES dataset spanning 2007–2018. The findings revealed a positive correlation between LAP and SUI. Specifically, as LAP values increased, the prevalence of SUI also increased, with the association remaining significant after adjustments for relevant confounding factors. The smooth-fitting curve identified a nonlinear relationship between LAP and SUI, and subgroup analysis confirmed that this positive association remained consistent across different demographic and lifestyle groups. Mediation analysis indicated that GGT partially mediated this relationship. Considering the often overlooked prevalence of SUI in women, monitoring LAP and controlling GGT levels could represent a simple yet effective method for early intervention in SUI in women.

Over the past decade, scholarly attention toward LAP as an indicator of lipid metabolism has markedly increased, with previous studies examining associations between LAP and various health conditions across different populations. In a 10-year prospective study involving 2,020 participants from the Mediterranean region, Kyrou et al. [19] observed that, after adjusting for multiple established cardiovascular disease risk factors, each 10-unit increment in LAP was associated with an 11% increased risk of developing cardiovascular disease. Similarly, Qiao et al. [20] reported that individuals with type 2 diabetes and a LAP >65 had a 6.03-fold greater risk of cardiovascular events compared to those with a LAP <26. Besides predicting cardiovascular disease risk, LAP has been established as a valuable marker for early diabetes identification. In a 12-year longitudinal study conducted in Korea, 608 (14.2%) initially nonobese participants developed type 2 diabetes during the follow-up period [21]. Despite these findings, the potential link between LAP and SUI had remained unexplored prior to our current investigation.

Considerable research has explored the association of SUI with various risk factors, including obesity-related indicators, lipid profiles, blood glucose levels, and lifestyle behaviors. Sun performed an extensive analysis examining the independent association between weight-adjusted waist index (WWI) and SUI, reporting a 38% increase in SUI prevalence per unit increase in WWI [22]. Chen et al. [23] conducted a study involving 7,973 adult women diagnosed with SUI, finding a positive relationship between serum TG levels and both the prevalence and severity of SUI. Zhu et al. [24] obtained similar results in a study that further explored the combined effects of hypertriglyceridemia and obesity on SUI prevalence among obese women under 50 years old. Zhu et al. [24] reported that this synergistic interaction accounted for approximately 67% of SUI cases, highlighting the potential for developing targeted preventive strategies for specific populations. Ying et al. [25] analyzed data spanning 10 years and discovered a link between blood glucose levels and SUI prevalence. After adjusting for confounding factors such as age, race, hypertension, and blood urea nitrogen, individuals with blood glucose levels exceeding 98 mg/dL had a 15.2% higher prevalence of SUI compared to those with blood glucose levels below 86 mg/dL. Additionally, Di et al. [26] noted that women who spent over 7 hours per day engaging in sedentary activities had a higher SUI prevalence. The breadth of these findings underscores the complex and multifaceted nature of SUI, as well as its potential risk factors. Introducing LAP as a metabolic indicator in this study provides valuable insight into the pathogenesis of SUI, contributing to the development of effective preventive and therapeutic strategies.

The exact mechanisms through which LAP is associated with SUI remain unclear. Abnormal lipid metabolism resulting from elevated LAP partially explains this relationship, potentially mediated by oxidative stress [27]. It is well established that obesity, a contributing factor to elevated LAP, increases intra-abdominal pressure on pelvic floor muscles and connective tissues, thereby increasing the likelihood of urinary incontinence [28]. Such mechanical pressure adversely affects bladder function and weakens urethral sphincter control. Additionally, visceral adipocytes release various adipokines, including leptin and adiponectin, which activate oxidative stress and inflammatory responses. These responses lead to vascular endothelial damage, impaired angiogenesis, and injury to the urethral epithelium, muscles, pelvic nerves, blood vessels, and ligaments [29]. In vitro experiments involving muscle-derived stem cells from young female Zucker Fatty (ZF) rats—a model for obesity/type 2 diabetes with SUI—showed that incubation with biotinylated antibodies (ZF4-SC) and exposure to lipid factors such as cholesterol and sodium palmitate induced apoptosis in these cells. Elevated lipid exposure also influenced multiple microRNAs related to myostatin, resulting in muscle-derived stem cell injury and subsequent alterations in muscle mass [30]. Wang et al. [31] conducted immunofluorescence staining of urethral tissues in transgenic aged female rats induced with severe obesity, finding increased lipid deposition within striated muscle fibers, thinning and atrophy of striated muscles, impaired urethral sphincter function, increased urinary frequency, reduced bladder capacity, frequent contractions, and urine overflow.

The process of urination in females results from the coordinated action of the parasympathetic, sympathetic, and pudendal nerves, which regulate contraction and relaxation of the detrusor muscle, urethral smooth muscle, and external urethral sphincter. Adipose tissue secretes inflammatory cytokines, such as tumor necrosis factor-alpha, IL-1, IL-6, and IL-8, which can damage nerve fibers and axons, leading to pelvic nerve injury and dysregulation of urinary function [32, 33]. Lipid metabolism disorders associated with obesity can activate oxidative stress, potentially promoting the activity of matrix metalloproteinases, leading to collagen degradation and compromising the structural integrity and elasticity of pelvic floor tissues [34]. Additional research suggests that lipid peroxidation is often accompanied by an imbalance between oxidation and antioxidation, where elevated oxidative stress factors inhibit collagen synthesis and impair pelvic support structures [35]. GGT plays a critical role in glutathione metabolism, functioning as a key regulator of the cellular antioxidant system. By breaking down extracellular glutathione into its constituent components—glutamate, cysteine, and glycine—GGT enables cells to reuse these precursors to synthesize new glutathione, thereby maintaining intracellular antioxidant capacity. However, under certain pathological conditions, increased demand for antioxidant defense leads to elevated GGT levels. When reactive oxygen species production exceeds the clearance capacity of glutathione, the compensatory effect of GGT becomes insufficient, resulting in an oxidative-antioxidative imbalance. Upon stimulation by factors secreted from adipocytes, excessive GGT may further exacerbate oxidative stress, leading to oxidative damage to DNA, proteins, and lipids. This oxidative damage impairs cellular structure and function, contributing to muscle weakness and reduced elasticity of connective tissues. Petermann-Rocha et al. [36] reported significantly elevated GGT levels in patients with sarcopenia, highlighting the detrimental impact of GGT on muscle tissues. Similarly, Hong et al. [37] demonstrated an association between elevated GGT and sarcopenic obesity, suggesting that oxidative stress induced by GGT might contribute to muscle damage. In this study, mediation analysis indicated that GGT, as a biomarker of oxidative stress, significantly mediated the association between LAP and SUI. This finding partially clarifies the potential mechanism linking LAP to SUI. However, the analysis did not identify serum bilirubin, white blood cells, or alkaline phosphatase as mediators. Nevertheless, this does not preclude the possibility that other oxidative stress markers or inflammatory factors may contribute to this relationship. Excessive visceral fat is often associated with chronic low-grade inflammation, characterized by elevated inflammatory markers such as C-reactive protein, interleukin-6, and tumor necrosis factor-alpha. These factors could influence the development of SUI through multiple pathways and warrant further investigation. This study utilized a large-scale population sample to investigate the relationship between LAP and SUI in women, as well as the potential mediating role of GGT, thereby providing insights into the underlying mechanisms of SUI. Based on these results, LAP could potentially serve as a screening tool for identifying individuals at high risk for SUI in clinical practice, facilitating targeted early interventions. For public health policymakers, promoting healthy lifestyles, maintaining optimal body weight, and reducing LAP levels could assist high-risk women in recognizing and effectively managing SUI at an earlier stage. Such strategies may contribute significantly to improved prevention and management of SUI in vulnerable populations. Despite identifying a positive association between LAP and SUI, this study's cross-sectional design inherently limits the ability to establish causality. Thus, it remains unclear whether LAP contributes to SUI risk via oxidative stress or if SUI might indirectly impact lipid metabolism, resulting in elevated LAP levels. Future longitudinal studies are necessary to investigate the temporal sequence and potential causal pathways among these variables. Additionally, excluding samples with missing variables might have introduced selection bias. Although potential confounding variables were extensively adjusted for, caution is still advised when interpreting the LAPSUI association, since not all confounding variables could be controlled. Furthermore, the mediation analysis incorporated a limited set of indicators, precluding a comprehensive exploration of the roles of oxidative stress and inflammatory factors. While GGT is an established marker of oxidative stress, its sensitivity and specificity for reflecting oxidative stress specifically related to SUI remain uncertain. Prospective clinical studies are warranted to further elucidate the relationship between LAP and SUI and to clarify the potential roles of oxidative stress and inflammatory factors.

In summary, this study demonstrates a positive association between elevated LAP levels and an increased prevalence of SUI among adult women in the United States. Additionally, the mediation analysis highlighted oxidative stress as a significant mediator in this association. The incorporation of LAP assessments into public health policy could therefore have substantial implications for enhancing women’s reproductive health.