{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T04:48:30Z","timestamp":1791607710791,"version":"4.3.4"},"reference-count":55,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,6,14]],"date-time":"2026-06-14T00:00:00Z","timestamp":1781395200000},"content-version":"vor","delay-in-days":13,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Comprehensive Physiology"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Heavy menstrual bleeding (HMB) is a common gynecological disorder increasingly recognized as a complex systemic condition involving dysregulated interactions between the immune system and the endometrium. Beyond traditional uterine\u2010centered explanations, growing evidence highlights the importance of immune\u2013endometrial crosstalk in regulating menstruation, vascular integrity, inflammation, tissue breakdown, and endometrial repair. This narrative review examines the role of monocyte and macrophage dysregulation in the pathophysiology of HMB and explores the broader interorgan dynamics contributing to disease progression. Monocytes and macrophages are central regulators of endometrial remodeling, angiogenesis, extracellular matrix turnover, and hemostasis throughout the menstrual cycle. Dysregulated recruitment, polarization, and activation of these immune cells contribute to excessive inflammatory signaling, impaired vascular stability, delayed tissue repair, and abnormal menstrual blood loss. Key inflammatory mediators implicated include tumor necrosis factor\u2010alpha, interleukin\u20106, CCL2, vascular endothelial growth factor, prostaglandins, matrix metalloproteinases, and NF\u2010\u03baB\u2010associated pathways. The review further highlights systemic interactions involving the bone marrow, liver, vascular endothelium, endocrine system, and gut\u2013immune axis, emphasizing HMB as a multisystem inflammatory disorder. Emerging evidence suggests that inflammatory biomarkers, immune profiling, and molecular characterization may improve disease stratification and support precision medicine approaches. Understanding HMB through the framework of immune\u2013endometrial crosstalk provides new opportunities for biomarker development, targeted immunomodulatory therapies, and individualized patient management aimed at improving reproductive and overall health outcomes.<\/jats:p>","DOI":"10.1002\/cph4.70200","type":"journal-article","created":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T05:09:52Z","timestamp":1781500192000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Immune\u2013Endometrial Crosstalk in Heavy Menstrual Bleeding: Interorgan Dynamics and Systemic Implications of Monocyte Dysregulation"],"prefix":"10.1002","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4538-0161","authenticated-orcid":false,"given":"Emmanuel Ifeanyi","family":"Obeagu","sequence":"first","affiliation":[{"name":"Division of Haematology, Department of Biomedical and Laboratory Science Africa University  Mutare Zimbabwe"},{"name":"Department of Molecular Medicine and Haematology, Faculty of Health Sciences University of the Witwatersrand  Johannesburg South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,14]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.18621\/eurj.1478034"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/biology14040319"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.107.744037"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2352-3026(16)30111-9"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.2147\/OAJC.S38993"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13287-018-1105-9"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tjog.2015.08.001"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2020.06.004"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvae106"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2024.e29686"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0049-3848(17)30072-5"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12905-019-0726-1"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ctim.2018.09.022"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2024.1331622"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells14010058"},{"issue":"4","key":"e_1_2_13_17_1","article-title":"Non\u2010Steroidal Anti\u2010Inflammatory Drugs for Heavy Bleeding or Pain Associated With Intrauterine\u2010Device Use","volume":"2006","author":"Grimes D. 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