Menstruation pulls the trigger for inflammation and pain in endometriosis
Abstract
Endometriosis is a chronic, hormone-dependent, inflammatory disease, characterized by the presence and growth of endometrial tissue outside the uterine cavity. It affects 5-10% of the female population of reproductive age and is frequently associated with moderate to severe pain, subfertility, and a marked reduction in health-related quality of life. Here, we propose a new pathophysiological concept of endometriosis, summarizing recent findings in one unifying picture. We propose menstruating tissue as the trigger for inflammatory pain in endometriosis through the activation of innate immune cells and peripheral nerve endings. We speculate how innovative treatment modalities beyond hormonal treatment will improve patients' lives.
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Because endometriosis can be found in asymptomatic women, the biochemical pathway of nerve stimulation by menstrual debris does not apply to asymptomatic women, suggesting inflammation from menstruating ectopic foci and menstrual debris may not be the sole cause of pelvic pain.
“Because endometriosis can be found in asymptomatic women, however, the biochemical pathway of nerve stimulation by the release of damage-associated molecular patterns and pathogen-associated molecular patterns by the menstrual debris (58) does not apply to the asymptomatic women, suggesting that the inflammation caused by ''menstruating'' ectopic foci and menstrual debris may not be the sole cause”
From Biomarkers in endometriosis: Challenges and opportunities (2017) · cites this paper as [58]
The continuous use of OC is suggested to achieve amenorrhea and relieve pain at withdrawal bleeding that may still afflict endometriosis patients using OC cyclically.
“In particular, the continuous use of OC is suggested to achieve amenorrhea and relieve pain at withdrawal bleeding that may still afflict endometriosis patients using OC cyclically (32,33).”
From A stepped-care approach to symptomatic endometriosis management: A participatory research initiative (2018) · cites this paper as [33]
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Estibeiro, V., Juntunen, A., Bond, J. C., & Harlow, B. L. (2022) · Journal of Women s Health · doi:10.1089/jwh.2020.9011 · Cited by 7 · see citing works
Marcolongo, P., Maellaro, E., & Luisi, S. V. (2021) · F&S Reviews · doi:10.1016/j.xfnr.2021.11.003 · Cited by 6 · see citing works
Endometriosis-associated pain and new therapeutic options: A review
Yarmolinskaya, M. I., Beganova, A. K., & Revenko, A. S. (2023) · GYNECOLOGY · doi:10.26442/20795696.2022.6.201975 · Cited by 5 · see citing works
Liu, Y., Cao, H., Zheng, S., & Zhuang, Y. (2024) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2024.151079 · Cited by 4 · see citing works
Wood, M., Garrett, N. E., Routh, D., & Jeffs, M. (2025) · International Journal of Offender Therapy and Comparative Criminology · doi:10.1177/0306624x251319406 · Cited by 4 · see citing works
Mandeville, J., Best, D., & Waterman, F. (2021) · Journal of Endometriosis and Pelvic Pain Disorders · doi:10.1177/22840265211024437 · Cited by 4 · see citing works
Anxiety-related behaviors without observation of generalized pain in a mouse model of endometriosis
Nuñez‐Badinez, P., Laux‐Biehlmann, A., Hayward, M. D., Buiakova, O. I., Zollner, T. M., & Nagel, J. (2023) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2023.1118598 · Cited by 4 · see citing works
Self-citation
- Authors
- Laux-Biehlmann, A., d’Hooghe, T., & Zollner, T. M.
- Affiliations
- Universitair Ziekenhuis Leuven (BE)
- Bayer (Germany) (DE)
- Corresponding author
- Zollner, Thomas M.
- Venue
- Trends in Pharmacological Sciences
- Publisher
- Elsevier BV
- Published
- 2015-05
- Volume
- 36
- Issue
- 5
- Pages
- 270-276
- ISSN
- 0165-6147 (ISSN-L)
- OpenAlex
- W2084007114
- Semantic Scholar
- 98811d6ffcaadeb55e103f5ce049196910a9cbe3
- Cited by
- 150
- References
- 109
- Citations by year
- 2026: 10 · 2025: 9 · 2024: 16 · 2023: 19 · 2022: 9 · 2021: 21 · 2020: 16 · 2019: 15 · 2018: 8 · 2017: 12 · 2016: 10 · 2015: 5
- FWCI
- 1.75
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Trends in Pharmacological Sciences (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Bayer
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Endometriosis Research and Treatment
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Menstrual Health and Disorders
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Ectopic Pregnancy Diagnosis and Management
- Keywords
- endometriosis, menstruation, inflammatory pain, innate immune cells, peripheral nerve endings, pathophysiology, hormone therapy, non-hormonal therapy, chronic inflammation
- MeSH terms
- Endometriosis, Female, Humans, Inflammation, Menstrual Cycle, Nociceptive Pain
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