Endometriosis is a chronic systemic disease: Clinical challenges and novel innovations
Abstract
Endometriosis is a common disease affecting 5-10% of women of reproductive age globally. However, despite its prevalence, diagnosis is typically delayed by years, misdiagnosis is common, and delivery of effective therapy is prolonged. Identification and prompt treatment of endometriosis are essential and facilitated by accurate clinical diagnosis. Endometriosis is classically defined as a chronic, gynaecological disease characterised by endometrial-like tissue present outside of the uterus and is thought to arise by retrograde menstruation. However, this description is outdated and no longer reflects the true scope and manifestations of the disease. The clinical presentation is varied, the presence of pelvic lesions is heterogeneous, and the manifestations of the disease outside of the female reproductive tract remain poorly understood. Endometriosis is now considered a systemic disease rather than a disease predominantly affecting the pelvis. Endometriosis affects metabolism in liver and adipose tissue, leads to systemic inflammation, and alters gene expression in the brain that causes pain sensitisation and mood disorders. The full effect of the disease is not fully recognised and goes far beyond the pelvis. Recognition of the full scope of the disease will facilitate clinical diagnosis and allow for more comprehensive treatment than currently available. Progestins and low-dose oral contraceptives are unsuccessful in a third of symptomatic women globally, probably as a result of progesterone resistance. Oral gonadotropin-releasing hormone (GnRH) antagonists constitute an effective and tolerable therapeutic alternative when first-line medications do not work. The development of GnRH antagonists has resulted in oral drugs that have fewer side-effects than other therapies and has allowed for rapid movement between treatments to optimise and personalise endometriosis care. In this Review, we discuss the latest understanding of endometriosis as a systemic disease with multiple manifestations outside the parameters of classic gynaecological disease.
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This localized immune dysregulation may influence endothelial function and contribute to subtle vascular remodeling observed in endometriosis.
“This localized immune dysregulation may influence endothelial function and contribute to subtle vascular remodeling observed in endometriosis [1].”
From Endometriosis and Cardiovascular Disease: Exploring Pathophysiological Interconnections and Risk Mechanisms (2025) · cites this paper as [1]
T lymphocytes, particularly Th1 and Th17 subsets, exacerbate this inflammatory milieu and may disrupt immune tolerance.
“Additionally, T lymphocytes, particularly Th1 and Th17 subsets, exacerbate this inflammatory milieu and may disrupt immune tolerance.”
From Endometriosis and Cardiovascular Disease: Exploring Pathophysiological Interconnections and Risk Mechanisms (2025) · cites this paper as [1]
Natural killer (NK) cells show reduced cytotoxic activity, facilitating the survival and proliferation of ectopic tissue.
“Natural killer (NK) cells show reduced cytotoxic activity, facilitating the survival and proliferation of ectopic tissue.”
From Endometriosis and Cardiovascular Disease: Exploring Pathophysiological Interconnections and Risk Mechanisms (2025) · cites this paper as [1]
Ectopic endometrial lesions are infiltrated by macrophages secreting pro-inflammatory cytokines such as interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), sustaining chronic local inflammation.
“Ectopic endometrial lesions are infiltrated by macrophages secreting pro-inflammatory cytokines such as interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), sustaining chronic local inflammation.”
From Endometriosis and Cardiovascular Disease: Exploring Pathophysiological Interconnections and Risk Mechanisms (2025) · cites this paper as [1]
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- Authors
- Taylor, H. S., Kotlyar, A. M., & Flores, V. A.
- Affiliations
- Yale University (US)
- Corresponding author
- Taylor, Hugh S
- Venue
- The Lancet
- Publisher
- Elsevier BV
- Published
- 2021-02
- Volume
- 397
- Issue
- 10276
- Pages
- 839-852
- ISSN
- 0099-5355 (ISSN-L)
- 0140-6736
- OpenAlex
- W3134885188
- Cited by
- 1,425
- References
- 45
- Citations by year
- 2026: 330 · 2025: 372 · 2024: 348 · 2023: 226 · 2022: 112 · 2021: 37
- FWCI
- 30.24
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Lancet (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Endometriosis Research and Treatment
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Ectopic Pregnancy Diagnosis and Management
- Health Sciences › Medicine › Obstetrics and Gynecology › Gynecological conditions and treatments
- Keywords
- endometriosis, systemic disease, chronic disease, delayed diagnosis, misdiagnosis, retrograde menstruation, systemic inflammation, hepatic metabolism, adipose tissue, brain gene expression, pain sensitization, mood disorders, progestins, oral contraceptives, progesterone resistance, GnRH antagonist, treatment resistance, personalized treatment
- MeSH terms
- Chronic Disease, Endometriosis, Female, Humans
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