Gamma-Glutamyl Transferase to High-Density Lipoprotein Ratio and Endometriosis Risk

A Liver–Lipid Biomarker Emerges as a Potential Indicator of Endometriosis Risk

Key Points

Highlights:

• A higher gamma-glutamyl transferase to high-density lipoprotein ratio was positively associated with the presence of endometriosis in a population-based sample. 
• The association remained significant after adjustment for demographic and metabolic confounders.

Imoortance:

• Identifying accessible metabolic biomarkers may improve understanding of systemic processes associated with endometriosis and help refine risk stratification in population settings.

What's Done Here?

• Investigators conducted a cross-sectional analysis using data from the National Health and Nutrition Examination Survey (NHANES). 
• The relationship between the gamma-glutamyl transferase to high-density lipoprotein ratio and self-reported endometriosis was evaluated using multivariable regression models.

Key Results:

• Women with endometriosis had significantly higher gamma-glutamyl transferase to high-density lipoprotein ratios compared with those without the disease. 
• Increasing ratio values were associated with higher odds of endometriosis in adjusted models.
• The relationship showed a dose-response pattern across ratio categories. 

Strengths and Limitations:

• The use of a nationally representative cohort enhances generalizability; and the adjustment for multiple metabolic and demographic confounders strengthens the observed association are the strengths of the study.
• Limitations are: the cross-sectional design precludes inference about temporal or causal relationships; endometriosis diagnosis was based on self-report, which may introduce misclassification bias; and residual confounding cannot be excluded.

From the Editor-in-Chief – EndoNews

"The pathophysiology of endometriosis has traditionally been explored through hormonal, immunologic, and local inflammatory mechanisms within the pelvic environment. Increasingly, however, attention has turned toward systemic metabolic signatures that may reflect broader biological processes associated with the disease. Population-based analyses offer a unique opportunity to examine these signals at scale and to generate hypotheses about potential links between metabolic homeostasis and endometriosis.

By evaluating a liver enzyme–lipid ratio derived from routinely available laboratory parameters, this study contributes to a growing body of literature examining metabolic correlates of endometriosis. The association identified in a nationally representative cohort suggests that markers related to oxidative stress and lipid metabolism may capture aspects of systemic physiology that intersect with the disease. Such findings reinforce the concept that endometriosis may not be solely a localized gynecologic disorder but part of a wider network of biological processes.

Importantly, the value of this work lies less in proposing a diagnostic tool and more in highlighting a potential metabolic context for endometriosis. Biomarkers derived from large epidemiologic datasets can illuminate patterns that are not readily apparent in smaller clinical cohorts, providing a framework for mechanistic exploration. Whether the observed association reflects shared risk factors, downstream effects of chronic inflammation, or parallel metabolic pathways remains uncertain and warrants further investigation.

Several considerations are essential when interpreting these findings. Cross-sectional analyses cannot establish temporal relationships, and reliance on self-reported diagnoses introduces the possibility of misclassification. Moreover, metabolic biomarkers are influenced by a wide range of environmental, lifestyle, and comorbid factors, underscoring the need for cautious interpretation and validation in prospective settings.

Despite these limitations, the study underscores the importance of integrating metabolic perspectives into endometriosis research. Future work that combines longitudinal designs, biomarker profiling, and clinical phenotyping may help clarify whether systemic metabolic signals contribute to disease susceptibility, progression, or symptom variability. In this context, the present findings serve as a stimulus for expanding research beyond traditional paradigms toward a more integrated understanding of the pathologic mechanisms underlying endometriosis."

Lay Summary

Growing evidence indicates that endometriosis may be shaped not only by local pelvic mechanisms but also by broader systemic metabolic and inflammatory processes.

Identifying readily available blood-based markers associated with the condition could help advance understanding of these systemic dimensions.

In a study published in the Journal of Obstetrics and Gynaecology, Dr. Ziyang Zheng and colleagues from the Department of stomatology, the third People’s Hospital of Yibin, China, analyzed data from the U.S. National Health and Nutrition Examination Survey (NHANES) to examine whether the ratio between gamma-glutamyl transferase, a liver enzyme linked to oxidative stress, and high-density lipoprotein cholesterol is associated with endometriosis.

The analysis included 3,815 participants, of whom 307 reported a clinician diagnosis of endometriosis based on a standardized NHANES reproductive health question.

The researchers found that women with endometriosis had higher values of this liver–lipid ratio compared with those without the condition. 

They also found that higher values of this liver–lipid ratio were positively associated with endometriosis in multivariable models. In the primary analysis, each unit increase in the log-transformed ratio corresponded to a higher likelihood of endometriosis, and sensitivity analyses supported the robustness of the association.

Higher ratio levels were associated with greater odds of endometriosis even after accounting for demographic and metabolic factors, and the relationship showed a gradual increase across ratio categories.

These findings suggest that biomarkers reflecting oxidative stress and lipid metabolism may be linked to endometriosis at the population level. Because the analysis is cross-sectional and relies on self-reported diagnosis, the results should be interpreted as an association rather than evidence of causation, and prospective studies are needed to clarify clinical relevance.

Research Source: https://pubmed.ncbi.nlm.nih.gov/41494840/