Nanyan Xiang Shiqi Su Yong Yang Yurui Luo Tingting Fu Le Wang Yifei Lin Jin Huang ^*

• West China Hospital, Sichuan University, Chengdu, Sichuan Province, China

Background: Stress urinary incontinence (SUI) is a common condition characterized by urethral sphincter failure and urine leakage. Its prevalence in females is higher than in males, and estimates of crude prevalence rates vary widely due to factors such as research methodologies, study populations, and underreporting by patients. This variability hinders research and impacts patient diagnosis, treatment, and quality of life. The complex etiology of SUI is not fully understood, and previous studies have primarily focused on non-invasive indicators. While emerging observational research suggests a correlation between SUI in female and abnormalities in lipid and blood metabolism, the underlying biological mechanisms and causal relationships require further investigation. This study aims to explore the causalities between SUI in female and lipid and blood metabolism. Methods: Using bidirectional univariate mendelian randomization (MR), we investigated the causal association between SUI liability in female (case/control = 5924/399509) from UK Biobank and lipid and glucose metabolism, indicated by total cholesterol (TC, N=61,166), low-density lipoproteins (LDL, N=58,381), high-density lipoproteins (HDL, N=60,812), triglycerides (TG, N=60,027), fasting glucose (FG, N=19,745) and fasting insulin (FI, N=38,238) from ENGAGE consortium. To account for potential confounding effects, multivariable MR (MVMR) analyses were performed, adjusting for body mass index (BMI) and separately among lipid and glucose metabolism.We found that increased genetically proxied TC, LDL and HDL levels were associated with elevated risk of SUI in female (OR: 1.090-1.117, all P<0.05), These associations were further supported by multivariable MVMR analyses with adjustment for BMI (OR: 1.087-1.114, all P<0.05). Conversely, increased FG and FI were associated with reduced SUI reliability in female (OR: 0.731-0.815, all P<0.05). When adjusting among lipid and glucose metabolism, only HDL and FI demonstrated causal effects. Reverse MR analyses provided no genetic evidence supporting causal effect of SUI in female on lipid and blood metabolism (all P>0.05). Conclusions: Our results reported that increased TC, LDL and HDL is linked to higher SUI susceptibility in women, while higher FG and FI levels have a protective effect. In overweight/obese women with metabolic abnormalities, the positive associations between TC, LDL and HDL levels and SUI indicate higher risk.