Markers of Local and Systemic Estrogen Metabolism in Endometriosis

Estrogen metabolites (EMs) can work independently from their parent hormones. We hypothesize that in endometriosis, estrogen is metabolized preferentially along hormonally active pathways. We recruited 62 women with endometriosis (proven laparoscopically and histologically) and 52 control women (normal findings with laparoscopy) among patients undergoing surgery for pelvic pain and/or infertility during the proliferative phase of the menstrual cycle. Urinary samples were collected preoperatively. Biopsies from eutopic endometrium of control women and women with endometriosis were collected during surgery. EMs in urine and endometrial tissues were extracted and determined using Liquid Chromatography-Electrospray Ionization Tandem Mass Spectrometry (LC-ESI-MS/MS). These included: 2-hydroxyestrone (2OHE1), 16-α hydroxyestrone (16α-OHE1), 2OHE1/16α-OHE1 ratio, 4-hydroxyestrone (4OHE1), 2-hydroxyestradiol (2OHE2), and 4-hydroxyestradiol (4OHE2). Eutopic endometrium of endometriosis patients, as compared to control endometrium, contained significantly higher level of 4OHE1 (0.03 (IQR: 0.03–0.265) versus 0.03 (IQR: 0.03–0.03) μg/g, respectively, P = 0.005), 2-OHE2 (0.241 (IQR: 0.1–0.960) versus 0.1 (IQR: 0.1–0.1) μg/g, respectively, P < 0.001), and 4-OHE2 (0.225 (IQR: 0.22–1.29) versus 0.0.2 (IQR: 0.2–0.2) μg/g, respectively, P < 0.001). Only 2OHE1 showed higher concentration in urine of women with endometriosis than controls (9.9 (IQR: 3.64–14.88) versus 4.5 (IQR: 1.37–17.00) μg/mg creatinine, respectively, P = 0.042). Eutopic endometrium of women with endometriosis metabolizes estrogen preferentially to the biologically active 2OHE2, and potentially genotoxic 4OHE1 and 4OHE2 metabolites. This contributes to further understanding of endometriosis etiology, its link to ovarian cancer, and could help identifying an endometrial biomarker of the disease. Similar content being viewed by others

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Ethical Statement The study was approved by the ethical review board, Assiut Faculty of Medicine, Assiut University, Egypt. The research was conducted in full compliance with ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments. Additional information Publisher’s Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Supplementary Information ESM 1 (download DOCX ) (DOCX 422 kb) Rights and permissions About this article Cite this article Othman, E.R., Markeb, A.A., Khashbah, M.Y. et al. Markers of Local and Systemic Estrogen Metabolism in Endometriosis. Reprod. Sci. 28, 1001–1011 (2021). https://doi.org/10.1007/s43032-020-00383-4 Received: Accepted: Published: Version of record: Issue date: DOI: https://doi.org/10.1007/s43032-020-00383-4