From lipid profiles to disease onset: Triglycerides as predictive biomarkers in endometriosis

Dyslipidaemia is related to endometriosis, but it is not known which lipid component is most relevant, and whether the observed correlation reflects the causal relationship. The relationship between triglycerides (TG) and endometriosis is studied through population research, and Mendelian randomization (MR) is used to evaluate the genetic evidence consistent with the causal relationship. We analyzed 2345 women from National Health and Nutrition Examination Survey 1999 to 2006 to assess lipid profiles and self-reported clinician-diagnosed endometriosis. Survey-weighted multivariable logistic regression was used with progressive covariate adjustment. Lipid-lowering medication use was additionally considered to address treatment-related confounding. For causal inference, 2-sample MR was conducted using genome-wide significant instruments for TG from large genome-wide association study resources and endometriosis summary statistics from FinnGen. Sensitivity analyses included assessments of heterogeneity and horizontal pleiotropy, as well as leave-one-out analyses. In the cross-sectional analysis, higher TG levels were associated with higher odds of endometriosis after multivariable adjustment. Compared with the lowest TG quartile, the highest quartile showed increased odds (odds ratio = 1.71, 95% confidence interval: 1.01-2.89). In MR analyses, genetically predicted TG was associated with endometriosis with consistent direction across methods; the inverse variance weighted estimate was odds ratio = 1.25 (95% confidence interval: 1.11-1.40). No statistically significant associations were observed for total cholesterol, low-density lipoprotein, or high-density lipoprotein. Subgroup analyses did not suggest clear effect heterogeneity by age, body mass index, or major metabolic comorbidities. In National Health and Nutrition Examination Survey 1999 to 2006, elevated TG was associated with higher odds of endometriosis. Two-sample MR provided genetic evidence consistent with a causal contribution of lifelong higher TG to endometriosis risk. These findings warrant confirmation in prospective cohorts and interventional studies before translation into clinical prevention strategies.