Each unit increase in remnant cholesterol was associated with a 135% higher likelihood of endometriosis, according to a recent study.
Researchers investigated the association between remnant cholesterol (RC) and endometriosis (EMs) using National Health and Nutrition Examination Survey (NHANES) data spanning 2001 to 2006. Published in Lipids in Health and Disease, the cross-sectional analysis included 1,840 participants, with RC calculated by subtracting low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol from total cholesterol. Endometriosis status was self-reported based on prior physician diagnoses. The study utilized multivariable logistic regression, subgroup analyses, generalized additive models (GAM), restricted cubic splines (RCS), and machine learning techniques to examine the link between RC and EMs.
Participants were stratified into RC quartiles: Q1 (0.150–0.380 mg/dL), Q2 (0.380–0.545 mg/dL), Q3 (0.545–0.813 mg/dL), and Q4 (0.813–2.073 mg/dL). After adjusting for confounders, each unit increase in RC was associated with an odds ratio of 2.35 for EMs (95% CI: 1.17–4.74; P = 0.017). Women in the highest RC quartile exhibited a 2.35-fold higher risk compared to those in the lowest quartile (95% CI: 1.18–4.65). The relationship between RC and EMs was confirmed as linear (P-nonlinear > 0.05), indicating consistent risk increases across RC levels.
Subgroup analyses showed consistent associations across most demographics, with stronger associations observed among women aged 30–40 years, non-Hispanic Black participants, those with early menarche, and individuals of lower socioeconomic status. Machine learning using XGBoost ranked RC as the most critical predictor of EMs among lipid and demographic variables. Diagnostic performance was moderate, with an area under the curve (AUC) of 0.614, surpassing traditional lipid markers like LDL-C (AUC: 0.592).
Strengths and Limitations
The study highlights RC as a potential non-invasive biomarker for EMs. However, its diagnostic power remains moderate, suggesting RC is more suitable as a supplemental indicator rather than a standalone tool. Additionally, the reliance on self-reported endometriosis diagnoses introduces potential recall bias, affecting data accuracy. The cross-sectional design limits causal inferences, and the dataset's timeframe (2001–2006) may constrain generalizability to contemporary populations.
Mechanistic Insights
The study posits potential mechanisms linking RC to EMs, including modulation of chronic inflammation, immune system regulation, and hormone metabolism. Elevated RC may exacerbate inflammatory processes via increased cytokine expression, facilitate ectopic tissue growth through macrophage polarization, and influence hormonal imbalances critical to endometriosis pathogenesis.
Further prospective studies are needed to validate RC's utility and explore its role in lipid metabolism, inflammation, and hormone-related mechanisms to enhance risk stratification for endometriosis.
Full disclosures can be found in the published study.
