Oral Presentation ESA-SRB-ANZOS 2025 in conjunction with ENSA

Understanding menstrual fluid for pathophysiology and diagnosis of endometriosis (128505)

Armita Foumani 1 2 , Chloe Hicks 1 2 , Roni Ratner 1 , Harriet Fitzgerald 1 2 , Caroline E Gargett 1 2 , Shanti Gurung 1 2
  1. Obstetrics and Gynaecology, Monash University, Clayton, Victoria, Australia
  2. The Ritchie Centre, Hudson Institute of Medical Research, Clayton, Victoria, Australia

Endometriosis, characterised by the presence of endometrial-like lesions outside of the uterus, is a debilitating and incurable gynaecological condition(1). Current diagnosis relies on invasive laparoscopic surgery(2). None of the proposed mechanisms thus far definitively explain the pathophysiology of the disease, nor have they been beneficial for non-surgical diagnostic methods(3). We aim to investigate menstrual fluid and its components as a non-invasive tool to better understand endometriosis and identify and utilise them as biomarkers for early diagnosis.

Menstrual blood was collected from women diagnosed with endometriosis (Endo,n=5) and healthy women (no symptoms of endometriosis, Ctrl,n=3) on day 2 of menses using a menstrual cup. Menstrual fluid supernatant was separated, and protein levels quantified. The abundance of 105 cytokines in menstrual fluid was assessed using multiplex array kits. Pixel density per cytokine signal was quantified, and statistical difference of the relative change in cytokine levels between groups was analysed using the two-tailed Mann-Whitney test with a confidence level of 99%.

Acrp30, C5/C5a, CHI3L1, IGFBP-3, IL-1β, MMP-9, OPN, PECAM-1, PF4, Serpin E1, SHBG, TFF3, THBS1, VCAM-1, VDB and VEGF were highly abundant in the menstrual fluid from both groups. Also present in lower abundance in both groups were interleukins (6,11,17A,18BPa and 19) and chemokines (CXCL9, CCL2, CCL20). These factors are associated with inflammation, decidualisation, tissue breakdown, blood loss regulation and tissue regeneration, supporting menstruation as a pro-inflammatory piecemeal event(4, 5). C-Reactive Protein (linked to infection), BAFF (B-cell activating factor), lipocalin-2 (released by neutrophils), IL-8 (a pro-inflammatory cytokine and chemokine for neutrophils), and angiogenin (pro-angiogenesis) were highly expressed in menstrual fluid from women with endometriosis compared to control groups, supporting the pro-inflammatory nature of endometriosis and the bacterial association of endometriosis(3, 6-9).

Menstrual fluid may serve as a minimally invasive diagnostic tool and provides valuable resources for biomarker identification for early diagnosis of endometriosis.

  1. Giudice LC, Horne AW, Missmer SA. Time for global health policy and research leaders to prioritize endometriosis. Nat Commun. 2023;14(1):8028.
  2. Bafort C, Beebeejaun Y, Tomassetti C, Bosteels J, Duffy JM. Laparoscopic surgery for endometriosis. Cochrane Database Syst Rev. 2020;10(10):CD011031.
  3. Endometriosis Initiative G. A Call for New Theories on the Pathogenesis and Pathophysiology of Endometriosis. J Minim Invasive Gynecol. 2024;31(5):371-7.
  4. Salamonsen LA. Menstrual Fluid Factors Mediate Endometrial Repair. Front Reprod Health. 2021;3:779979.
  5. Evans J, Salamonsen LA. Inflammation, leukocytes and menstruation. Rev Endocr Metab Disord. 2012;13(4):277-88.
  6. Tanaka T, Umesaki N, Mizuno K, Fujino Y, Ogita S. Anti-endometrial IgM autoantibodies in endometriotic patients: a preliminary study. Clin Exp Obstet Gynecol. 2000;27(2):133-7.
  7. Liao CJ, Li PT, Lee YC, Li SH, Chu ST. Lipocalin 2 induces the epithelial-mesenchymal transition in stressed endometrial epithelial cells: possible correlation with endometriosis development in a mouse model. Reproduction. 2014;147(2):179-87.
  8. Muraoka A, Suzuki M, Hamaguchi T, Watanabe S, Iijima K, Murofushi Y, et al. Fusobacterium infection facilitates the development of endometriosis through the phenotypic transition of endometrial fibroblasts. Sci Transl Med. 2023;15(700):eadd1531.
  9. Riccio LGC, Baracat EC, Chapron C, Batteux F, Abrao MS. The role of the B lymphocytes in endometriosis: A systematic review. J Reprod Immunol. 2017;123:29-34.