Endometriosis-associated Pain: Mechanism, Neuroimmune Signature, and Translational Precision Strategies
Harriet J Omenge1, Paulina A Kempa1, Jae-Wook Jeong1
1Department of Obstetrics, Gynecology, and Women's Health, University of Missouri.
Endocrine Reviews
|June 10, 2026
Summary
Endometriosis pain involves complex hormonal and immune factors, not just lesions. Understanding these mechanisms is key to developing better treatments for chronic pelvic pain in women.
Area of Science:
- Gynecology
- Pain Medicine
- Immunology
Background:
- Endometriosis affects 10% of women globally, causing chronic pelvic pain.
- Pain severity often doesn't correlate with lesion size, suggesting complex pain mechanisms.
- Current understanding of endometriosis-associated pain is incomplete, leading to diagnostic delays and limited treatment options.
Purpose of the Study:
- To review current evidence on endometriosis-associated pain mechanisms, clinical presentation, and therapies.
- To integrate insights into endocrine, immune, and neural pathways involved in pain.
- To propose a precision medicine framework for individualized pain management.
Main Methods:
- Literature review synthesizing clinical, mechanistic, and therapeutic data.
- Integration of findings from inflammatory, immune, neuroimmune, hormonal, and sensitization pathways.
- Highlighting advances from preclinical models and multi-omics technologies.
Main Results:
- Endometriosis pain arises from a convergence of endocrine dysregulation (estrogen dominance, progesterone resistance), immune activation, neuroangiogenesis, and neural plasticity.
- Peripheral sensitization, driven by estrogen-dependent inflammation and progesterone resistance, leads to central nervous system sensitization.
- Pain can persist independently of lesion activity due to sustained neural input and sensitization.
Conclusions:
- Estrogen dominance and progesterone resistance are central drivers of endometriosis pain biology.
- A comprehensive understanding of neuroimmune and endocrine pathways is crucial for effective pain management.
- Precision medicine, incorporating biomarkers and tailored therapies, is needed for individualized pain relief in endometriosis.
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