Advanced Endometriosis and Cardiometabolic Risk: Evidence From Lipid Biomarkers

Not all endometriosis is equal: advanced disease shows a cardiometabolic signal.

Key Points

Highlights: 

• Advanced endometriosis phenotypes are associated with adverse lipid profiles.

Importance:

• Lipid biomarkers may reflect disease severity and phenotype in endometriosis, highlighting a potential cardiometabolic dimension of advanced disease.

What’s done here:

• Lipid profiles were analyzed in 476 women from the ENDO cohort, with laparoscopically or MRI-confirmed endometriosis classified by stage and phenotype.
• Associations between endometriosis status, severity, and phenotype and adverse lipid profiles were assessed using adjusted prevalence models accounting for key demographic and metabolic confounders.

Key results:

• Endometriosis diagnosis alone was not associated with adverse lipid profiles.
• Moderate to severe disease (rASRM stage III/IV) showed a higher prevalence of elevated triglycerides and very low-density lipoprotein (VLDL).
• Ovarian endometriosis, alone or combined with deep infiltrating endometriosis (DIE), was associated with adverse lipid profiles across multiple markers, most prominently apolipoprotein B (ApoB) and triglycerides.
• Superficial or minimal/mild disease was not associated with lipid abnormalities.

Strengths and Limitations:

• Strengths are: Large, well-characterized cohort with objective confirmation of endometriosis by surgery or MRI;  standardized staging (rASRM), detailed phenotype classification, enabling severity- and subtype-specific analyses.and comprehensive assessment of multiple lipid biomarkers, including apolipoproteins, with adjustment for key demographic and metabolic confounders.
• Limitations are: The comparison group included women with other gynecologic conditions rather than exclusively healthy controls; lipid measurements were obtained in a non-fasting state, which may influence some parameters; the subgroup with ovarian endometriosis plus deep infiltrating disease was small (n = 17), limiting power and precision for phenotype-specific estimates.

From the Editor-in-Chief – EndoNews

"This study contributes to the growing recognition that endometriosis is a heterogeneous disease, in which severity and phenotype—rather than diagnosis alone—may carry distinct systemic signatures. By demonstrating that adverse lipid profiles cluster specifically in advanced-stage disease and ovarian endometriosis, the authors shift the focus away from endometriosis as a uniform entity toward a phenotype-driven biological framework.

Importantly, the absence of lipid abnormalities in women with minimal or superficial disease underscores that cardiometabolic alterations are not an inherent feature of endometriosis per se. Instead, the findings suggest that certain endometriosis phenotypes may share underlying inflammatory, metabolic, or vascular pathways that extend beyond the pelvis. This distinction is critical for avoiding overgeneralization and for refining future risk stratification strategies.

The study’s reliance on lipid biomarkers measured at the time of diagnosis provides a valuable snapshot of early metabolic differences, but it does not establish causality or predict cardiovascular outcomes. As such, the results should be interpreted as hypothesis-generating, highlighting associations rather than clinical endpoints. Whether these lipid patterns represent a consequence of severe disease, a shared upstream susceptibility, or an epiphenomenon remains unresolved.

From a broader perspective, this work reinforces the need for integrated phenotyping approaches in endometriosis research—linking surgical classification, molecular features, and systemic biomarkers. Longitudinal studies will be essential to determine whether the observed lipid alterations translate into meaningful differences in long-term cardiometabolic health and whether they warrant tailored clinical consideration."

Overall, the study advances the field by emphasizing that disease context matters, and that understanding endometriosis requires moving beyond diagnosis toward biologically informed subtypes with potentially distinct systemic implications.

Lay Summary

A new study from the United States suggests that advanced forms of endometriosis, particularly ovarian endometriosis (endometriomas) alone or combined with deep infiltrating endometriosis (DIE), are associated with unfavorable blood lipid profiles, which are known markers of cardiometabolic risk. The research was published in the Journal of Gynecology Obstetrics and Human Reproduction.

The investigators examined lipid biomarkers in 476 women enrolled in the ENDO cohort to determine whether cardiometabolic alterations vary according to endometriosis stage and disease phenotype. Importantly, having a diagnosis of endometriosis alone was not associated with abnormal lipid levels.

In contrast, women with moderate to severe disease (stage III/IV) and those with ovarian endometriosis, with or without DIE, showed a higher prevalence of elevated triglycerides, very low-density lipoprotein (VLDL), and apolipoprotein B (ApoB). These lipid patterns were not observed in women with superficial or minimal/mild disease.

Because lipid measurements were obtained at the time of endometriosis diagnosis, the findings suggest that metabolic differences may already be present in early adulthood, particularly in more severe disease phenotypes. The authors emphasize that lipid profiles may reflect disease severity or shared underlying biological pathways, rather than endometriosis per se.

While these results do not establish a causal link with cardiovascular disease, they highlight the need for further research in larger and more diverse populations to clarify whether cardiometabolic risk differs by endometriosis phenotype and whether this has implications for long-term health.

Research Source: https://pubmed.ncbi.nlm.nih.gov/41407106/