Association Between the C-Reactive Protein–Albumin–Lymphocyte Index and Endometriosis: Insights from the 1999–2006 National Health and Nutrition Examination Survey

Xinyu Xu, Hongyan Cheng, Xue Ye, Xiaohong Chang Department of Obstetrics and Gynecology, People’s Hospital, Peking University, Beijing, People’s Republic of ChinaCorrespondence: Xiaohong Chang, Department of Obstetrics and Gynecology, People’s Hospital, Peking University, Beijing, People’s Republic of China, Email [email protected]: The C-reactive protein–albumin–lymphocyte (CALLY) index serves as an integrated indicator, reflecting the interplay between systemic inflammation, immune competence, and nutritional health. While validated in other chronic diseases, its relevance to endometriosis remains unexplored. We aimed to assess its association with endometriosis using nationally representative data.Methods: This cross-sectional analysis used data from four cycles of the National Health and Nutrition Examination Survey (NHANES, 1999– 2006), including 4,602 US adults. The CALLY index was derived by integrating measurements of C-reactive protein (CRP) levels, serum albumin concentrations, and lymphocyte counts. Associations with endometriosis were estimated using weighted multivariable logistic regression across three progressively adjusted models. The discriminatory ability of CALLY was assessed using receiver operating characteristic (ROC) analyses and compared against that of other commonly used inflammatory biomarkers. Smoothed curve fitting and subgroup/interaction analyses assessed pattern and heterogeneity.Results: Log-transformed CALLY values (ln CALLY) levels showed a statistically significant inverse relationship with endometriosis prevalence (OR = 0.87; 95% CI: 0.79– 0.96). Individuals in the top quartile of ln CALLY (Q4) had a 40% lower risk of endometriosis than those in the bottom quartile (Q1) (OR = 0.60, 95% CI: 0.41– 0.87). Compared to other commonly used indices, CALLY exhibited superior discriminatory performance, achieving an AUC of 0.7219 (95% CI: 0.6970– 0.7468) in the fully adjusted model. Curve fitting indicated that higher CALLY index levels were linked to a reduced likelihood of endometriosis. Subgroup analysis further confirmed the consistency and independence of this relationship (all p values for interactions >  0.05).Conclusion: A significant inverse association was observed between the CALLY index and endometriosis prevalence among American adults, supporting its potential as a novel inflammatory marker for identifying individuals at elevated risk. However, as a cross-sectional study, causality cannot be inferred. Future prospective cohorts across diverse populations are needed to evaluate its clinical utility for risk prediction and early identification.Keywords: endometriosis, CALLY index, NHANES, association, nutrition, inflammation