Association between remnant cholesterol–based lipid indicators and testosterone deficiency in middle-aged and older men: a cross-sectional study

Background: Remnant cholesterol (RC), representing cholesterol carried in triglyceride-rich lipoproteins, has emerged as an important marker of residual cardiometabolic risk. Recent population-based studies have suggested an association between RC and testosterone deficiency (TD); however, evidence from real-world clinical populations and the potential involvement of inflammatory pathways remains limited. Methods: This multicenter cross-sectional study enrolled 387 men aged 50-75 years from urology and andrology outpatient clinics at three hospitals between December 2024 and December 2025. Testosterone deficiency was diagnosed according to American Urological Association guidelines, defined as total testosterone <300 ng/dL accompanied by relevant clinical symptoms. Fasting blood samples were obtained to assess lipid profiles, sex hormones, and inflammatory markers. Remnant cholesterol was calculated as total cholesterol minus HDL-C and LDL-C. Multivariable logistic regression analyses were used to examine the association between RC and TD. Receiver operating characteristic (ROC) curve analysis evaluated the discriminative ability of RC compared with traditional lipid parameters. Mediation analyses were performed using the Hayes PROCESS macro (model 4) with 5,000 bootstrap resamples to assess the potential mediating roles of high-sensitivity C-reactive protein (hs-CRP) and interleukin-6 (IL-6). Results: Among the 387 participants, 183 were diagnosed with TD. Higher RC levels were significantly associated with increased odds of TD after adjustment for demographic factors, lifestyle variables, metabolic comorbidities, medication use, and triglyceride levels (adjusted OR per 1 mmol/L increase: 3.33, 95% CI: 2.35-4.71). When categorized into quartiles, RC showed a clear dose-response association with TD (all P < 0.001). In ROC analysis, RC demonstrated moderate discriminative ability for identifying TD (AUC = 0.733, 95% CI: 0.684-0.782), outperforming total cholesterol (AUC = 0.696), triglycerides (AUC = 0.634), and LDL-C (AUC = 0.605). Mediation analyses indicated that hs-CRP and IL-6 partially mediated the association between RC and TD, accounting for 23.57% and 16.49% of the total effect, respectively. Conclusions: In this multicenter cross-sectional study, elevated remnant cholesterol was associated with a higher prevalence of TD and showed superior discriminative performance compared with traditional lipid parameters. Longitudinal studies are needed to clarify temporal relationships and underlying mechanisms.