TY - JOUR
T1 - Markers of Local and Systemic Estrogen Metabolism in Endometriosis
AU - Othman, Essam R.
AU - Markeb, Ahmad Abo
AU - Khashbah, Maha Y.
AU - Abdelaal, Ibrahim I.
AU - ElMelegy, Tarek T.
AU - Fetih, Ahmed N.
AU - Van der Houwen, Lisette E.
AU - Lambalk, Cornelis B.
AU - Mijatovic, Velja
N1 - Funding Information: The study was supported by a grant (ID# 5525) from Science and Technology Development Fund (STDF), Egyptian Ministry of Higher Education to ERO. Publisher Copyright: © 2020, Society for Reproductive Investigation. Copyright: Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2021/4
Y1 - 2021/4
N2 - 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.
AB - 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.
KW - Endometriosis
KW - Endometrium
KW - Estrogen
KW - Metabolites
KW - Urine
UR - http://www.scopus.com/inward/record.url?scp=85096298593&partnerID=8YFLogxK
U2 - https://doi.org/10.1007/s43032-020-00383-4
DO - https://doi.org/10.1007/s43032-020-00383-4
M3 - Article
C2 - 33216295
SN - 1933-7191
VL - 28
SP - 1001
EP - 1011
JO - Reproductive Sciences
JF - Reproductive Sciences
IS - 4
ER -