Endometriosis in the era of precision medicine and impact on sexual and reproductive health across the lifespan and in diverse populations

The FASEB Journal, Journal Year: 2023, Volume and Issue: 37(9)

Published: Aug. 29, 2023

Endometriosis is a common estrogen-dependent disorder wherein uterine lining tissue (endometrium) found mainly in the pelvis where it causes inflammation, chronic pelvic pain, pain with intercourse and menses, infertility. Recent evidence also supports systemic inflammatory component that underlies associated co-morbidities, e.g., migraines cardiovascular autoimmune diseases. Genetics environment contribute significantly to disease risk, explosion of omics technologies, underlying mechanisms symptoms are increasingly being elucidated, although novel effective therapeutics for infertility have lagged behind these advances. Moreover, there stark disparities diagnosis, access care, treatment among persons color transgender/nonbinary identity, socioeconomically disadvantaged populations, adolescents, disturbing low awareness health care providers, policymakers, lay public about endometriosis, which, if left undiagnosed under-treated can lead significant fibrosis, infertility, depression, markedly diminished quality life. This review summarizes endometriosis epidemiology, compelling its pathogenesis, pathophysiology age precision medicine, recent biomarker discovery, therapeutic approaches, issues around reproductive justice marginalized populations this spanning past 100 years. As we enter next revolution biomedical research, rich molecular clinical datasets, single-cell omics, population-level data, well positioned benefit from data-driven research leveraging computational artificial intelligence approaches integrating data predicting response medical surgical therapies, prognosis recurrence.

Language: Английский

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Endometriosis: recent advances that could accelerate diagnosis and improve care

Trends in Molecular Medicine, Journal Year: 2024, Volume and Issue: 30(9), P. 875 - 889

Published: July 10, 2024

Endometriosis is a common disorder associated with pain, gastrointestinal and urinary symptoms, infertility, fatigue. It defined by the presence of endometrial-like lesions found predominantly in pelvis. Mechanisms that contribute to disease aetiology include changes hormonal, inflammatory, pain pathways. In this article, we focus on recent developments imaging technologies, our improved understanding mechanisms contributing drug therapies are clinical trials, insights from studies gut offer potential support self-management strategies. We postulate improvements quality life patients will be accelerated reframing endometriosis as multi-system learning treatments targeting symptoms shared between endometriosis, neuroinflammatory, disorders.

Language: Английский

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Update on the pathogenesis of endometriosis-related infertility based on contemporary evidence

Frontiers in Endocrinology, Journal Year: 2025, Volume and Issue: 16

Published: March 10, 2025

Endometriosis, the most prevalent cause of infertility, is associated with anatomical distortion leading to adhesions and fibrosis, as well endocrine abnormalities immune disorders. This review discusses mechanisms underlying endometriosis-related infertility. Firstly, alterations in hypothalamic-pituitary-ovarian axis lead secretion gonadotropins steroid hormones, adverse effects on ovulation implantation, fertility decline. Secondly, dysregulation hypothalamic-pituitary-adrenal induces elevated serum cortisol prolactin levels patients endometriosis, accounting for its regulation stress, depression, anxiety. Abnormal interactions between endometrial cells system change local microenvironment, resulting epithelial-mesenchymal transition inflammation. Activated epithelial cells, stromal immunocytes produce various chemokines, cytokines, or autoantibodies, creating an unfavorable environment embryo implantation. These findings suggest that spectrum play a crucial role Thirdly, oxidative stress has ovarian reserve subsequent embryonic development, predicting another promising strategy An unbalanced redox state, including impaired mitochondrial function, dysregulated lipid metabolism, iron-induced generates pro-oxidative which negatively impacts oocyte quality sperm viability. Thus, updated understanding involved this disease will help develop effective strategies manage

Language: Английский

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New Potential Pharmacological Options for Endometriosis Associated Pain

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(13), P. 7068 - 7068

Published: June 27, 2024

Endometriosis is a chronic inflammatory disorder characterized by the abnormal growth of endometrial-like tissue outside uterine cavity, affecting 10-15% women reproductive age. Pain most common symptom. Treatment options include surgery, which has limited effectiveness and high recurrence rates, pharmacotherapy. Hormonal therapies, commonly used for symptom management, can have side effects contraceptive outcomes, contributing to infertility associated with endometriosis, pain lesions often reappearing after treatment cessation. Among its etiological factors, immunological dysregulation plays significant role, representing an interesting target developing new therapeutic strategies. This review critically analyzes recent studies provide updated synthesis ongoing research into potential pharmacotherapies focusing on lesion progression, relief, improving quality life. Immunotherapy, natural anti-inflammatory antioxidant compounds drug repurposing show promise in addressing limitations current treatments targeting potentially offering non-invasive solutions managing endometriosis. Promising results been obtained from vitro animal model studies, but clinical trials are still limited. More effort needed translate these findings practice effectively reduce disease alleviate symptoms preserve capacity, patients' overall wellbeing.

Language: Английский

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Gut microbiome in endometriosis: a cohort study on 1000 individuals

BMC Medicine, Journal Year: 2024, Volume and Issue: 22(1)

Published: July 18, 2024

Abstract Background Endometriosis, defined as the presence of endometrial-like tissue outside uterus, is one most prevalent gynecological disorders. Although different theories have been proposed, its pathogenesis not clear. Novel studies indicate that gut microbiome may be involved in etiology endometriosis; nevertheless, connection between microbes, their dysbiosis, and development endometriosis understudied. This case–control study analyzed women with without to identify microbial targets disease. Methods A subsample 1000 from Estonian Microbiome cohort, including 136 864 control women, was analyzed. Microbial composition determined by shotgun metagenomics functional pathways were annotated using Kyoto Encyclopedia Genes Genomes (KEGG) database. Partitioning Around Medoids (PAM) algorithm performed cluster profile population. The alpha- beta-diversity differential abundance analyses assess (species KEGG orthologies (KO)) both groups. Metagenomic reads mapped estrobolome-related enzymes’ sequences potential microbiome-estrogen metabolism axis alterations endometriosis. Results Diversity did detect significant differences (alpha-diversity: all p -values > 0.05; beta-diversity: PERMANOVA, R 2 < 0.0007, 0.05). No species or detected after multiple testing adjustment (all FDR Sensitivity analysis excluding at menopause (> 50 years) confirmed our results. Estrobolome-associated sequence significantly groups Conclusions Our findings do provide enough evidence support existence a microbiome-dependent mechanism directly implicated To best knowledge, this largest metagenome on conducted date.

Language: Английский

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Association between triglyceride-glucose index and risk of endometriosis in US population: results from the national health and nutrition examination survey (1999–2006)

Frontiers in Endocrinology, Journal Year: 2024, Volume and Issue: 15

Published: May 28, 2024

Background and Aims The association of the triglyceride-glucose (TyG) index, a promising novel biomarker for insulin resistance, with risk endometriosis has not been investigated to date. This nationwide study aimed explore between TyG index risk. Methods Data were obtained from National Health Nutrition Examination Survey (1999–2006). Female participants who provided complete data on enrolled in analysis. Multivariate logistic regression analyses utilized assess endometriosis, adjusted by multiple potential confounders. Meanwhile, in-depth subgroup conducted. Results A total 1,590 eligible included, among whom 135 (8.5%) women diagnosed endometriosis. fully multivariate model showed was significantly associated (odds ratio [OR] Q4 versus Q1 2.04, 95% confidence interval [CI]: 1.15–3.62; P trend=0.013). In analyses, positive also found parous (OR 2.18, CI: 1.20–3.96), without diabetes 2.12, 1.19–3.79), smoke currently 3.93, 1.33–11.58), drink 2.54, 1.27–5.07), use oral contraceptives 1.91, 1.04–3.51). Additionally, increasing trends odds across quartiles observed above-mentioned subgroups (all trend&lt;0.05). Conclusions population-based that higher representing an increased level US population. Our findings suggested might be tool assessment Prospective studies are warranted further verify these findings.

Language: Английский

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TET3-overexpressing macrophages promote endometriosis

Journal of Clinical Investigation, Journal Year: 2024, Volume and Issue: 134(21)

Published: Aug. 14, 2024

Endometriosis is a debilitating, chronic inflammatory disease affecting approximately 10% of reproductive-age women worldwide with no cure. While macrophages have been intrinsically linked to the pathophysiology endometriosis, targeting them therapeutically has extremely challenging due their high heterogeneity and because these disease-associated (DAMs) can be either pathogenic or protective. Here, we report identification characterized by TET3 overexpression in human endometriosis lesions. We show that factors from microenvironment upregulated expression, transforming into DAMs. stimulated proinflammatory cytokine production via feedback mechanism involving inhibition let-7 miRNA expression. Remarkably, cells relied on for survival hence were vulnerable knockdown. demonstrated Bobcat339, synthetic cytosine derivative, triggered degradation both mouse macrophages. This was dependent von Hippel-Lindau (VHL) E3 ubiquitin ligase whose expression also TET3-overexpressing Furthermore, depleting through myeloid-specific Tet3 ablation using Bobcat339 strongly inhibited progression mice. Our results defined as key contributors attractive therapeutic targets endometriosis. findings may applicable other diseases where DAMs important roles.

Language: Английский

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Observational and Genetic Analyses of Traumatic Experiences and Endometriosis

JAMA Psychiatry, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 5, 2025

Importance Although psychological traumas have been associated with endometriosis, limited information is available regarding the role of trauma type and genetic predisposition. Objective To examine relationship between traumatic experiences endometriosis using observational genetically informed analyses. Design, Setting, Participants For this case-control study, analyses were performed May 13, 2023, September 30, 2024. Genotypic phenotypic was combined from UK Biobank individual-level data (up to 8276 patients 240 117 female controls) genome-wide a large meta-analysis (European ancestry: 21 779 449 087 controls; East Asian 1713 1581 FinnGen cohort (16 588 111 583 controls European descent). Main Outcomes Measures Phenotypic associations via multiple regression; latent-class analysis (LCA) investigate co-occurrence patterns different in cases correlation polygenic risk scoring (PRS) assess pleiotropy linking events endometriosis. Results Up women (mean [SD] age, 53.2 [13.0] years) 56.5 [9.6] investigated study. Women more likely report childhood adulthood stressful (eg, contact odds ratio [OR], 1.28; 95% CI, 1.02-1.26). Our LCA highlighted association emotional physical (225 [8%] vs 3948 [5%]; P &amp;lt; 2.2 × 10 −16 ) sexual (414 [5%] 3158 [4%]; = 2.9 −3 ). Unaffected (controls) assigned “no trauma” latent class (563 [20%] 18 949 [24%]; 7.4 −14 (rg) linked trauma-related outcomes, including posttraumatic stress disorder (meta-analysis rg 0.31, 7.1 ; 0.26, 4.7 −15 maltreatment 0.23, 1.3 −6 0.16, 1 −4 Endometriosis PRS increased disease (β ), but no interaction observed types events. Conclusions Relevance The present study comprehensively impact on In particular, our findings highlight potential which appears be independent

Language: Английский

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СТАНДАРТИЗАЦІЯ ОРГАНОЗБЕРІГАЮЧОГО ЛАПАРОСКОПІЧНОГО ЛІКУВАННЯ ЖІНОК ІЗ БОЛЬОВИМ СИНДРОМОМ, АСОЦІЙОВАНИМ ІЗ ГЛИБОКИМ ЕНДОМЕТРІОЗОМ

Актуальні питання педіатрії акушерства та гінекології, Journal Year: 2025, Volume and Issue: 2, P. 38 - 47

Published: Jan. 22, 2025

Мета дослідження – підвищити ефективність органозберігаючого хірургічного лікування жінок із глибоким ендометріозом, що супроводжується больовим синдромом, шляхом створення покрокового алгоритму оперативного лапароскопічного втручання. Матеріали та методи. На базі нашого центру було проведено проспективне обсерваційне одноцентрове когортне дослідження, до якого увійшли 210 репродуктивного віку прооперованих приводу глибокого ендометріозу за новою методикою стандартизації період січня 2020 грудня 2023 р., класифікацію всіх випадків проводили згідно з #Enzian. Досліджено інтраопераційні, ранні віддалені післяопераційні показники. Результати їх обговорення. Ми отримали значне статистично значуще поліпшення показників больового синдрому через 6 місяців після втручання шкалою ВАШ від 0 10 (хронічний тазовий біль операції 6,87+/-1,41, 2,41+/-1,59 (p<0,001), дисменорея 8,46+/-1,16 2,08+/-1,36 диспареунія 7,42+/-1,07 2,22+/-1,69 дисхезія 3,2+/-3,6 0,8+/-2,0 дизурія 1,2+/-2,6 0,4+/-1,4 (p=0,026)). Глибокий ендометріоз є, безумовно, найтяжчою формою визначається як розростання тканини, схожої на ендометрій, по під поверхнею очеревини; зазвичай це вузли, здатні проникати у сусідні структури пов’язані фіброзом і порушенням нормальної анатомії, чим зумовлена складність цього захворювання. Ураження органів тканинних структур призводить змін анатомії елімінацією контурів значного спотворення операційного поля, становить серйозну проблему при хірургічному лікуванні навіть для досвідчених хірургів. Це, звичайно, треба враховувати перед- інтраопераційному етапі. Наразі не існує регламентованих документів світі щодо ендометріозу, а саме стандартизованих підходів такого однозначної думки про ступінь радикальності операцій. Щодо хірургії ми маємо єдиний документ ESGE, ESHRE and WES 2020, але він присвячений деяким технічним особливостям містить стратегії втручання, яка є вкрай необхідною хірурга. Оскільки кожен хірург оперує пацієнток спираючись свій власний розсуд, таке може мати занадто суб’єктивний характер завжди йти користь пацієнтам, тому вважаємо, настав час ендометріозу. Наступним нашим дослідженням стане ретроспективне порівняння хірургічних пацієнток, стандартизованою загальноприйнятими методами. Висновки. Алгоритм стандартизованого має покращити показники результати, значно полегшити роботу хірургів об’єктивізувати лікування.

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Voices of women with endometriosis in Latin America: tales of invalidation, high costs, and diagnostic delays

Women & Health, Journal Year: 2025, Volume and Issue: 65(3), P. 224 - 226

Published: March 10, 2025

Language: Английский

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