RÉSUMÉ
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.
Sujet(s)
Endométriose/métabolisme , Endomètre/métabolisme , Oestrogènes/métabolisme , Hydroxyoestrones/métabolisme , Marqueurs biologiques/métabolisme , Chromatographie en phase liquide , Femelle , Humains , Spectrométrie de masse en tandemRÉSUMÉ
BACKGROUND: Benign nonendometriotic ovarian cysts are very common and often require surgical excision. However, there has been a growing concern over the possible damaging effect of this surgery on ovarian reserve. OBJECTIVE: The aim of this metaanalysis was to investigate the impact of excision of benign nonendometriotic ovarian cysts on ovarian reserve as determined by serum anti-Müllerian hormone level. DATA SOURCES: MEDLINE, Scopus, ScienceDirect, and Embase were searched electronically. STUDY DESIGN: All prospective and retrospective cohort studies as well as randomized trials that analyzed changes of serum anti-Müllerian hormone concentrations after excision of benign nonendometriotic cysts were eligible. Twenty-five studies were identified, of which 10 were included in this analysis. DATA EXTRACTION: Two reviewers performed the data extraction independently. RESULTS: A pooled analysis of 367 patients showed a statistically significant decline in serum anti-Müllerian hormone concentration after ovarian cystectomy (weighted mean difference, -1.14 ng/mL; 95% confidence interval, -1.36 to -0.92; I(2) = 43%). Subgroup analysis including studies with a 3-month follow-up, studies using Gen II anti-Müllerian hormone assay and studies using IOT anti-Müllerian hormone assay improved heterogeneity and still showed significant postoperative decline of circulating anti-Müllerian hormone (weighted mean difference, -1.44 [95% confidence interval, -1.71 to -1.1; I(2) = 0%], -0.88 [95% confidence interval, -1.71 to -0.04; I(2) = 0%], and -1.56 [95% confidence interval, -2.44 to -0.69; I(2) = 22%], respectively). Sensitivity analysis including studies with low risk of bias and excluding studies with possible confounding factors still showed a significant decline in circulating anti-Müllerian hormone. CONCLUSION: Excision of benign nonendometriotic ovarian cyst(s) seems to result in a marked reduction of circulating anti-Müllerian hormone. It remains to be established whether this reflects a real compromise to ovarian reserve.