Association between early age at menarche and overactive bladder risk in women: insights from NHANES and Mendelian...

Early age at menarche (AAM) has been linked to adverse metabolic trajectories that may influence bladder function, but the association between AAM and overactive bladder (OAB), and the mediating role of body mass index (BMI), remains unclear. This study aimed to examine the association of AAM with OAB risk, quantify BMI mediation, and evaluate causality using Mendelian randomization (MR).

We analyzed data from 9,647 women in the National Health and Nutrition Examination Survey (NHANES, 2011-2018). OAB was defined by an Overactive Bladder Symptom Score (OABSS) ≥3. Multivariable logistic regression and restricted cubic spline (RCS) analyses evaluated the AAM-OAB relationship, adjusting for demographic, clinical, and lifestyle confounders. Mediation analysis quantified BMI's role. MR analysis, using 156 single-nucleotide polymorphisms (SNPs) from the Integrative Epidemiology Unit (IEU) Open Genome-Wide Association Study (GWAS) database, validated causality.

Each one-year increase in AAM was associated with a 5% reduced OAB risk [odds ratio (OR): 0.95, 95% confidence interval (CI): 0.93-0.98, P<0.001]. Compared to the earliest AAM quartile (Q1), Q2 (OR: 0.86, 95% CI: 0.77-0.97, P=0.01) and Q4 (OR: 0.81, 95% CI: 0.70-0.93, P=0.003) showed lower OAB risk. RCS analysis confirmed a linear inverse relationship (P-non-linear =0.107). BMI mediated 30.89% of the AAM-OAB association (indirect effect: -0.004, 95% CI: -0.005 to -0.004, P<2×10-16). MR analysis supported causality (OR: 0.998, 95% CI: 0.996-0.999, P=0.008), with no pleiotropy (MR-Egger intercept P=0.87).

Early AAM increases OAB risk, partially mediated by BMI, with causal evidence from MR. Screening for early AAM and managing weight may reduce OAB risk.