Systemic Inflammation and Psychological Trauma in Endometriosis: A Narrative Review Towards Integrated Management

In: Advanced Pharmaceutical and Biomedical Letters · 2026 · vol. 2026(1) , pp. 54–64 · doi:10.59493/advpbl/2026.1.7 · W7204039050
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This narrative review synthesizes evidence linking endometriosis-driven systemic inflammation to psychiatric comorbidities, highlighting a self-perpetuating neuro-immune cycle that necessitates integrated, trauma-informed multidisciplinary care.

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This narrative review synthesizes evidence from 32 studies to examine the bidirectional relationship between systemic inflammation and psychiatric comorbidities in endometriosis. The authors report that endometriotic lesions release pro-inflammatory cytokines like IL-6 and TNF-α, which drive HPA axis dysregulation and neuroinflammation, thereby exacerbating hyperalgesia, fatigue, depression, and anxiety. Conversely, psychological trauma and diagnostic delays further intensify inflammatory profiles, creating a self-perpetuating cycle that necessitates integrated, multidisciplinary care including trauma-informed screening and specialized psychiatric support. This paper is centrally about endometriosis — specifically exploring the intersection of its systemic inflammatory nature with psychological trauma and mental health outcomes.

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Abstract

Endometriosis is increasingly recognized as a systemic inflammatory disease with complex immune and neuroendocrine dysregulation. This narrative review synthesized evidence on the bidirectional relationship between systemic inflammation and psychiatric comorbidities, drawing from 32 peer-reviewed studies (2020–2026). Results indicate that endometriotic lesions release interleukin-6 (IL-6) and Tumor Necrosis Factor-alpha (TNF-α) into systemic circulation, driving chronic immune activation and Hypothalamic-Pituitary-Adrenal (HPA) axis dysregulation. This leads to significant (p < 0.05) alteration of cortisol secretion, neuroinflammation, and structural changes in the hippocampus and amygdala, which in turn perpetuate hyperalgesia, fatigue, and heightened vulnerability to depression and anxiety. Conversely, psychological trauma and diagnostic delays exacerbate inflammatory profiles, forming a self-perpetuating cycle. To break this neuro-immune cycle, clinicians must transition from isolated surgical management to integrated, multidisciplinary care. This requires operationalizing trauma-informed practices through routine Adverse Childhood Experiences (ACE) screening, validated pelvic pain psychological distress tools, and explicit referral pathways to specialized psychiatric support and pelvic-floor physical therapy. Future research must address a critical gap in the literature by identifying the precise dose-response thresholds linking specific circulating cytokines to localized psychiatric symptom severity; these key gaps regarding optimal screening tools and intervention timing warrant future prospective studies.
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Systemic Inflammation and Psychological Trauma in Endometriosis: A Narrative Review Towards Integrated Management DOI: https://doi.org/10.59493/advpbl/2026.1.7Keywords: Chronic pelvic pain, Endometriosis, Immune dysregulation, Multidisciplinary pain management, Pro-inflammatory cytokines, Trauma-informed careAbstract Endometriosis is increasingly recognized as a systemic inflammatory disease with complex immune and neuroendocrine dysregulation. This narrative review synthesized evidence on the bidirectional relationship between systemic inflammation and psychiatric comorbidities, drawing from 32 peer-reviewed studies (2020–2026). Results indicate that endometriotic lesions release interleukin-6 (IL-6) and Tumor Necrosis Factor-alpha (TNF-α) into systemic circulation, driving chronic immune activation and Hypothalamic-Pituitary-Adrenal (HPA) axis dysregulation. This leads to significant (p < 0.05) alteration of cortisol secretion, neuroinflammation, and structural changes in the hippocampus and amygdala, which in turn perpetuate hyperalgesia, fatigue, and heightened vulnerability to depression and anxiety. Conversely, psychological trauma and diagnostic delays exacerbate inflammatory profiles, forming a self-perpetuating cycle. To break this neuro-immune cycle, clinicians must transition from isolated surgical management to integrated, multidisciplinary care. This requires operationalizing trauma-informed practices through routine Adverse Childhood Experiences (ACE) screening, validated pelvic pain psychological distress tools, and explicit referral pathways to specialized psychiatric support and pelvic-floor physical therapy. Future research must address a critical gap in the literature by identifying the precise dose-response thresholds linking specific circulating cytokines to localized psychiatric symptom severity; these key gaps regarding optimal screening tools and intervention timing warrant future prospective studies. References Liu F, Yuan S, Yan Q, Yang S, Yan W, Xiang T, Wu Z, Li G, Ren W, Wang W, 2026. Global Trends in Endometriosis Burden, 1990-2021: A Sociodemographic Analysis Using GBD 2021 Data and Projections to 2036. International Journal of Women's Health, 18: 560463. https://doi.org/10.2147/IJWH.S560463 World Health Organization. 2025, Endometriosis. Available at https://www.who.int/news-room/fact-sheets/detail/endometriosis (Accessed 2 July, 2026). Scarparo IMT, Zanella C, Cardoso MS, Martins AS, Leandro ACF, 2026. Underdiagnosed endometriosis: Repercussions of diagnostic delay on chronic pain, fertility, and quality of life. 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Cognitive Behavioral Therapy in Endometriosis, Psychological-Based Intervention: A Systematic Review. Intervenção psicológica baseada na terapia cognitivo-comportamental na endometriose: Uma revisão sistemática. Revista brasileira de ginecologia e obstetrícia: revista da Federação Brasileira das Sociedades de Ginecologiae Obstetrícia, 44(3):295–303. Downloads Published How to Cite Issue Section License Copyright (c) 2026 Daniel I. Oraekei, Ogbonnaya Mba, Onyeka C. Obidiegwu, Harrison O. Abone This work is licensed under a Creative Commons Attribution 4.0 International License. All articles published in Advanced Pharmaceutical and Biomedical Letters (AdvPBL) are distributed under an Open Access Creative Commons License BY/4.0. Users are allowed to freely download, read, distribute the materials in any medium or format, remix, reuse the articles or quote the articles, so long as proper attribution is given to the original creators (authors and publishers). 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