Inflammatory Markers in Women with Endometriosis Before and After the COVID-19 Pandemic: A Matched Cohort Study from the Tehran Lipid and Glucose Study
4 affiliations
- 1Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
- 2Reproductive Endocrinology Research Center, Research Institute for Endocrine Molecular Biology, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
- 3Department of Immunology, Golestan University of Medical Sciences, Gorgan, Iran
- 4Foundation for Research and Education Excellence, Vestavia Hills, Al, USA
Abstract
Background: Endometriosis (EM) is a common chronic inflammatory disorder affecting women. The coronavirus disease 2019 (COVID-19) pandemic may have been associated with changes in systemic inflammatory regulation.
Objectives: This study aimed to measure and compare serum interleukin-6 (IL-6) levels, mRNA levels of vascular endothelial growth factor (VEGF), C-X-C motif chemokine 5 (CXCL5), and substance P (SP), as well as markers of neutrophil extracellular trap formation (NETosis), in patients with EM before and after the onset of the COVID-19 pandemic.
Methods: We used data from the Tehran Lipid and Glucose Study (TLGS). Among 2558 women in the TLGS, 465 had a diagnosis of endometriosis. Of these, 13 women had biobanked samples available from both the pre-pandemic (Phase 6, 2016 - 2018) and post-pandemic (Phase 7, 2021 - 2023) periods and were included as matched pairs within the same individuals. The primary exposure was the post-pandemic calendar period; individual COVID-19 infection data were not collected. Real-time PCR was used to quantify the expression of genes associated with SP (TAC1), neurokinin 1 receptor (TACR1), VEGF, and CXCL5 in peripheral blood mononuclear cells. Markers of NETosis, including neutrophil elastase (NE), myeloperoxidase (MPO), peptidyl arginine deiminase 4 (PAD4), and matrix metallopeptidase 9 (MMP9), were assessed. Serum IL-6 concentrations were measured by enzyme-linked immunosorbent assay.
Results: Gene expression analysis showed no significant changes in TAC1, TACR1, VEGF, or CXCL5; all 95% confidence intervals (CIs) included unity, and the study was underpowered to detect small differences. Evaluation of NETosis-related genes in neutrophils stimulated with patient sera showed no significant differences in PAD4, MMP9, or MPO expression; however, NE expression was significantly elevated after the pandemic (fold change = 1.5; 95% CI, 1.01 to 2.25; P = 0.048). Other NETosis markers and IL-6 did not differ significantly (eg, IL-6 median paired difference, +0.58 pg/mL; 95% CI, -0.89 to +2.34 pg/mL; P = 0.750); thus, all non-significant results are inconclusive.
Conclusions: A preliminary signal of increased neutrophil elastase expression was observed after the pandemic, whereas other inflammatory and NETosis markers remained inconclusive. In this small investigation, the relative contributions of COVID-19 infection, vaccination, psychosocial stress, and lifestyle changes could not be disentangled. These hypothesis-generating findings require confirmation in larger, well-characterized cohorts.
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BibTeX
@article{matouri2026inflammatory,
title = {{Inflammatory Markers in Women with Endometriosis Before and After the COVID-19 Pandemic: A Matched Cohort Study from the Tehran Lipid and Glucose Study}},
author = {Maryam Matouri and Ameneh Koochaki and Shahla Noori Ardebili and Mostafa Haji Molla Hoseini and Marzieh Saei Ghare Naz and Moein Malekzadeh and Maryam Mousavi and Fahimeh Ramezani Tehrani and Nariman Mosaffa},
journal = {International Journal of Endocrinology and Metabolism},
year = {2026},
month = jun,
doi = {10.5812/ijem-171933},
url = {https://doi.org/10.5812/ijem-171933},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Inflammatory Markers in Women with Endometriosis Before and After the COVID-19 Pandemic: A Matched Cohort Study from the Tehran Lipid and Glucose Study
AU - Maryam Matouri
AU - Ameneh Koochaki
AU - Shahla Noori Ardebili
AU - Mostafa Haji Molla Hoseini
AU - Marzieh Saei Ghare Naz
AU - Moein Malekzadeh
AU - Maryam Mousavi
AU - Fahimeh Ramezani Tehrani
AU - Nariman Mosaffa
PY - 2026
DA - 2026/06/23
JO - International Journal of Endocrinology and Metabolism
DO - 10.5812/ijem-171933
UR - https://doi.org/10.5812/ijem-171933
AB - Background: Endometriosis (EM) is a common chronic inflammatory disorder affecting women. The coronavirus disease 2019 (COVID-19) pandemic may have been associated with changes in systemic inflammatory regulation. Objectives: This study aimed to measure and compare serum interleukin-6 (IL-6) levels, mRNA levels of vascular endothelial growth factor (VEGF), C-X-C motif chemokine 5 (CXCL5), and substance P (SP), as well as markers of neutrophil extracellular trap formation (NETosis), in patients with EM before and after the onset of the COVID-19 pandemic. Methods: We used data from the Tehran Lipid and Glucose Study (TLGS). Among 2558 women in the TLGS, 465 had a diagnosis of endometriosis. Of these, 13 women had biobanked samples available from both the pre-pandemic (Phase 6, 2016 - 2018) and post-pandemic (Phase 7, 2021 - 2023) periods and were included as matched pairs within the same individuals. The primary exposure was the post-pandemic calendar period; individual COVID-19 infection data were not collected. Real-time PCR was used to quantify the expression of genes associated with SP (TAC1), neurokinin 1 receptor (TACR1), VEGF, and CXCL5 in peripheral blood mononuclear cells. Markers of NETosis, including neutrophil elastase (NE), myeloperoxidase (MPO), peptidyl arginine deiminase 4 (PAD4), and matrix metallopeptidase 9 (MMP9), were assessed. Serum IL-6 concentrations were measured by enzyme-linked immunosorbent assay. Results: Gene expression analysis showed no significant changes in TAC1, TACR1, VEGF, or CXCL5; all 95% confidence intervals (CIs) included unity, and the study was underpowered to detect small differences. Evaluation of NETosis-related genes in neutrophils stimulated with patient sera showed no significant differences in PAD4, MMP9, or MPO expression; however, NE expression was significantly elevated after the pandemic (fold change = 1.5; 95% CI, 1.01 to 2.25; P = 0.048). Other NETosis markers and IL-6 did not differ significantly (eg, IL-6 median paired difference, +0.58 pg/mL; 95% CI, -0.89 to +2.34 pg/mL; P = 0.750); thus, all non-significant results are inconclusive. Conclusions: A preliminary signal of increased neutrophil elastase expression was observed after the pandemic, whereas other inflammatory and NETosis markers remained inconclusive. In this small investigation, the relative contributions of COVID-19 infection, vaccination, psychosocial stress, and lifestyle changes could not be disentangled. These hypothesis-generating findings require confirmation in larger, well-characterized cohorts.
SN - 1726-913X
SN - 1726-9148
ER -