Dose-Response And Threshold Effects of a C-reactive Protein–Triglyceride–Glucose Composite Index and Endometriosis Risk: A Cross-Sectional Study

Summary

Using NHANES 1999–2006 data, we evaluate how a composite inflammation–metabolism index (CTI) relates to endometriosis, characterize a risk threshold around CTI 8.53, compare CTI with other inflammatory indices, and provide a reproducible, survey-weighted protocol with internal validation for population-level risk stratification.

Abstract

Endometriosis is a prevalent gynecological disorder associated with chronic low-grade inflammation, yet diagnosis is often delayed because symptoms are non-specific and definitive confirmation typically relies on invasive procedures. Composite indices that jointly capture inflammatory and metabolic disturbance may improve population-level risk stratification and inform earlier clinical evaluation. Using cross-sectional data from 1,805 women aged 20–54 years in NHANES 1999–2006 (146 self-reported endometriosis; 1,659 controls), we examined survey-weighted associations between a C-reactive protein–triglyceride–glucose composite index and endometriosis risk. Survey-weighted multivariable logistic regression was used to estimate odds ratios and 95% confidence intervals for the index modeled as a continuous exposure and by quartiles. Restricted cubic splines and piecewise regression were applied to evaluate non-linear patterns and to identify potential threshold effects. To contextualize the incremental value of the composite index, we compared its performance with established inflammatory indices and with component markers, including C-reactive protein and the triglyceride–glucose index, using receiver operating characteristic analyses. This workflow provides a reproducible, survey-weighted analytic framework for evaluating composite inflammation–metabolism indicators and their threshold behavior in relation to endometriosis risk.

Introduction

Endometriosis is a chronic, inflammation-related gynecological condition that affects an estimated 5%–10% of women of reproductive age¹. Diagnosis traditionally depends on laparoscopic and histologic confirmation, which, although definitive, is invasive and costly and is often preceded by many years of non-specific symptoms and repeated consultations². Epidemiologic evidence suggests that the interval from symptom onset to diagnosis commonly spans several years and can extend to nearly a decade in many settings³. These diagnostic delays can exacerbate pain, reduce quality of life, and increa....

Protocol

The NHANES protocol was approved by the National Center for Health Statistics (NCHS) Research Ethics Review Board, and written informed consent was obtained from all participants. This work was a secondary analysis of de-identified public-use data; therefore, no additional institutional ethical approval was required. All authors read and approved the final manuscript.

1. Study design and data source

This study was conducted as a secondary analysis of NHANES, a series of cross-sectional, nationally representative surveys administered by the U.S. Centers for Disease Control and Prevention and oversee....

Results

Baseline characteristics

A total of 1,805 women were included in the analysis, of whom 146 (8.1%) reported a diagnosis of endometriosis and 1,659 (91.9%) did not. Women without endometriosis served as the control group. Baseline characteristics are summarized in Table 1. Women with endometriosis were older than controls (40.7 ± 8.3 vs. 36.8 ± 9.6 years, P < 0.001). The distribution of race/ethnicity differed between groups: 70.5% of women with endometriosis.......

Discussion

This study demonstrates that the C-reactive protein–triglyceride–glucose index (CTI), a composite measure of inflammatory and metabolic status, is independently and positively associated with the odds of endometriosis in a nationally representative sample of women (Table 2). This interpretation is consistent with previous evidence implicating oxidative stress, immune activation, and metabolic dysregulation in the development and progression of endometriosis⁹. By integr.......

Materials

List of materials used in this article

Name	Company	Catalog Number	Comments
Body mass index data	NHANES (CDC/NCHS)	NHANES Continuous datasets portal: https://wwwn.cdc.gov/nchs/nhanes/continuousnhanes/default.aspx?BeginYear=1999
C-reactive protein assay data	NHANES (CDC/NCHS)	Same NHANES portal (1999–2006 cycles; lab files): https://wwwn.cdc.gov/nchs/nhanes/continuousnhanes/default.aspx?BeginYear=1999
Demographic questionnaire data	NHANES (CDC/NCHS)	Same NHANES portal (DEMO files): https://wwwn.cdc.gov/nchs/nhanes/continuousnhanes/default.aspx?BeginYear=1999
Endometriosis questionnaire item	NHANES (CDC/NCHS)	Same NHANES portal (Reproductive Health questionnaire): https://wwwn.cdc.gov/nchs/nhanes/continuousnhanes/default.aspx?BeginYear=1999
Fasting plasma glucose assay data	NHANES (CDC/NCHS)	Same NHANES portal (fasting glucose lab files): https://wwwn.cdc.gov/nchs/nhanes/continuousnhanes/default.aspx?BeginYear=1999
Hemoglobin assay data	NHANES (CDC/NCHS)	Same NHANES portal (CBC/hematology files where applicable): https://wwwn.cdc.gov/nchs/nhanes/continuousnhanes/default.aspx?BeginYear=1999
Neutrophil count data	NHANES (CDC/NCHS)	Same NHANES portal (CBC with differential where applicable): https://wwwn.cdc.gov/nchs/nhanes/continuousnhanes/default.aspx?BeginYear=1999
Platelet count data	NHANES (CDC/NCHS)	Same NHANES portal (CBC files): https://wwwn.cdc.gov/nchs/nhanes/continuousnhanes/default.aspx?BeginYear=1999
Triglyceride assay data	NHANES (CDC/NCHS)	Same NHANES portal (triglycerides lab files): https://wwwn.cdc.gov/nchs/nhanes/continuousnhanes/default.aspx?BeginYear=1999
R statistical software	R Foundation for Statistical Computing	R project: https://www.r-project.org/ ; CRAN download: https://cran.r-project.org/
Restricted cubic spline modeling	R package rms	CRAN rms package page: https://cran.r-project.org/package=rms
Segmented regression analysis	R package segmented	CRAN segmented package page: https://cran.r-project.org/package=segmented
Survey design analysis	R package survey	CRAN survey package page: https://cran.r-project.org/package=survey