Abstract：
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.
摘要：
雌激素代谢物（EM）可以独立于其母体激素而起作用。我们假设在子宫内膜异位症中，雌激素优先沿着激素活性途径代谢。我们招募了62名患有子宫内膜异位症的女性（腹腔镜和组织学证实）和52名对照女性（腹腔镜检查正常发现），这些女性在月经周期的增生期因盆腔疼痛和/或不孕症而接受手术的患者中。术前收集尿样。手术期间收集对照妇女和子宫内膜异位症妇女的在位子宫内膜活检。提取尿液和子宫内膜组织中的EM，并使用液相色谱-电喷雾电离串联质谱法（LC-ESI-MS/MS）进行测定。其中包括：2-羟基雌酮（2OHE1），16-α羟基雌酮（16α-OHE1），2OHE1/16α-OHE1比值，4-羟基雌酮（4OHE1），2-羟基雌二醇(2OHE2),和4-羟基雌二醇(4OHE2)。子宫内膜异位症患者的在位子宫内膜，与对照子宫内膜相比，含有明显更高水平的4OHE1（0.03（IQR：0.03-0.265）对0.03（IQR：0.03-0.03）μg/g，分别,P=0.005),2-OHE2（0.241（IQR：0.1-0.960）与0.1（IQR：0.1-0.1）μg/g，分别,P<0.001)，和4-OHE2（0.225（IQR：0.22-1.29）与0.0.2（IQR：0.2-0.2）μg/g，分别,P<0.001)。子宫内膜异位症患者尿液中只有2OHE1的浓度高于对照组（9.9（IQR：3.64-14.88）与4.5（IQR：1.37-17.00）μg/mg肌酐，分别,P=0.042)。子宫内膜异位症女性的在位子宫内膜优先代谢雌激素至具有生物活性的2OHE2，以及潜在遗传毒性的4OHE1和4OHE2代谢物。这有助于进一步了解子宫内膜异位症的病因，它和卵巢癌有联系，并且可以帮助识别该疾病的子宫内膜生物标志物。
