Elevated High-Density Lipoprotein Cholesterol May Reduce Risk of Stress Urinary Incontinence

Investigators have published new data in the International Journal of Medical Sciences demonstrating a causal link between elevated high-density lipoprotein cholesterol (HDL-C) levels and a reduced risk of stress urinary incontinence (SUI), with heightened protection observed in patients with overweight and/or obesity. The data highlights the unique role of HDL-C levels in preventing SUI, especially in individuals with a high body mass index (BMI).¹

Association Between SUI and HDL-C Warrants Further Research

SUI, a condition that particularly impacts women, involves the involuntary leakage of urine during physical acts. Examples include laughing, coughing, or sneezing. With up to 10% to 40% of women globally affected by SUI—and prevalence increasing with age and obesity—there is a critical need for research on prevention strategies and risk factor amelioration. Factors such as pelvic floor dysfunction and childbirth are established risks for SUI, but more recent evidence points to metabolic health as a potential new avenue for SUI prevention.^1-3

HDL-C is known as an indicator of cardiovascular protection in contrast to low-density lipoprotein cholesterol (LDL-C). More recent analyses have begun to uncover the involvement of HDL-C in non-cardiovascular settings, including infections, diabetes, and chronic kidney disease, offering potential for HDL-C to serve as a predictive measure of SUI development. Unfortunately, available evidence on the relationship between HDL-C and SUI is conflicting, with numerous investigative groups coming to varying conclusions.^1,4

A dual-evidence study, integrating cross-sectional analyses from the National Health and Nutrition Examination Survey (NHANES) and a 2-sample Mendelian randomization, was imitated by the current authors to evaluate the association between HDL-C levels and SUI prevalence, with particular focus on patients with overweight or obesity. Furthermore, the authors sought to explore whether BMI levels can modify the protective effect of HDL-C. In total, 18,415 women from the NHANES survey were included in the analysis, of which 7658 (41.59%) reported SUI.¹

Higher HDL-C Levels Reduced Risk of SUI

Firstly, HDL-C and SUI associations were examined. Restricted cubic splines (RCS) analysis demonstrated a nonlinear association between HDL-C and SUI in a crude model (P for overall < .001; P for nonlinear < .001). There was a steep risk decrease observed at lower HDL-C levels, with a plateau in risk reduction at higher HDL-C. A stepwise weighted multivariate logistic regression indicated that, for each 1 mg/dL increase in HDL-C, SUI risk decreased by 0.8% (95% CI, 0.989—0.994; P < .001), which remained significant in the partially adjusted and fully adjusted models.¹

Regarding specific HDL-C thresholds, individuals with HDL-C of 67 mg/dL or more had a 17.3% (95% CI, 0.747—0.917) reduced risk of SUI. The authors also conducted a stepwise analysis investigating the risk of SUI with increasing HDL-C levels, with Q4 indicating the highest LDL-C level and Q1 indicating the lowest. Observations from a fully adjusted model indicate that the risk of SUI in the highest LDL-C level was 25.1% (95% CI, 0.652—0.859) lower compared with the lowest level, while the second level indicated no meaningful protective effect (odds ratio [OR] = 0.950 [95% CI, 0.847—1.066]; P = .380).¹

A subgroup analysis was conducted across demographic and clinical data, which revealed that the protective effect of HDL-C was especially strong in individuals with overweight or obesity (BMI of 25 kg/m² or more: OR = 0.992, P = .006; BMI of 30 kg/m² or more: OR = 0.991, P = .001). Notably, younger women—aged 60 or less—demonstrated a heightened risk reduction of SUI. The authors also determined that, when SUI was stratified by varying leakage frequencies, HDL-C levels were inversely related with all frequency levels of SUI, with increasing HDL-C levels inducing a parallel decrease in the frequency of SUI.¹

A causal relationship between HDL-C and SUI was indeed observed by the study authors, suggesting a protective effect with HDL-C against SUI. The investigators caution, however, that these protective effects are not linear across the board; they noted an “HDL-C” paradox observed in their unadjusted RCS analysis, which underscores the need for precision and thorough further investigation. Despite this limitation, the use of a large, nationally representative sample from a large-scale analysis allows for these observations to be deemed reliable and a solid base for future research.¹

“These robust findings suggest that maintaining optimal HDL-C levels may serve as an effective preventive strategy against SUI, especially in high-BMI populations,” the study authors concluded. “While our results highlight the therapeutic potential of HDL-C, future studies should further elucidate the underlying mechanisms and validate these associations across diverse demographic groups.”¹

REFERENCES

1. Huang J, Wang Z, Liu Z, et al. Protective Role of High-Density Lipoprotein Cholesterol in Stress Urinary Incontinence with Special Emphasis on Overweight/Obese Individuals. Int J Med Sci. 2025;22(12):3304-3315. doi:10.7150/ijms.116324

2. Li J, Wang D, Tian H, et al. Association between lipid accumulation products and stress urinary incontinence: a cross-sectional study from NHANES 2005 to 2018. Lipids in Health and Disease. 2024;23(358). doi:10.1186/s12944-024-02350-3

3. Bo K, Frawley HC, Haylen BT. An International Urogynecological Association (IUGA)/International Continence Society (ICS) joint report on the terminology for the conservative and nonpharmacological management of female pelvic floor dysfunction. Neurourol Urodyn. 2017;36(2):221-244. doi:10.1002/nau.23107

4. Eckardstein AV, Nordestgaard BG, Remaley AT, Catapano AL. High-density lipoprotein revisited: biological functions and clinical relevance. Eur Heart J. 2023;44(16):1394-1407. doi:10.1093/eurheartj/ehac605