► Expression of CYP1A1, CYP3A7, COMT and MB-COMT levels were higher in endometriosis. ► Expression of SULT1E1, SULT2B1, UGT2B7, NQO1, and GSTP1 was decreased. ► Three NQO1 isoforms were detected; ...NQO1c appears to be endometriosis-specific. ► This imbalance between phase I and II enzymes may lead to excessive ROS formation. ► Hydroxy-estrogens and ROS can promote proliferation of ovarian endometriotic cells.
Oxidative metabolism of estrogens was studied in 31 ovarian endometriosis and 29 normal endometrium samples, by qPCR. Expression was monitored for genes encoding five estrogen hydroxylating, five hydroxy (OH)-estrogen conjugating, and three estrogen quinone detoxifying enzymes. CYP1B1, COMT, NQO1, and GSTP1 protein levels were determined using Western blotting and immunohistochemistry staining. Increased expression of CYP1A1, CYP3A7 and COMT, and higher levels of MB-COMT were seen in endometriosis, as compared to normal endometrium. Expression of CYP1B1, CYP3A5, SULT1A1 and NQO2 was unchanged, with comparable CYP1B1 protein levels. Expression of SULT1E1, SULT2B1, UGT2B7, NQO1, and GSTP1 was decreased. Three NQO1 isoforms were detected; NQO1c appears to be endometriosis-specific. Our data indicate a disturbed balance between phase I and II metabolizing enzymes in endometriosis, potentially leading to excessive OH-estrogen and altered ROS formation, and stimulation of proliferation of ectopic endometrium. This is the first report on disturbed expression of estrogen oxidative metabolism genes in ovarian endometriosis.
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•We performed targeted metabolomics study to identify peritoneal fluid biomarkers of endometriosis.•The case-control study comprised 29 ovarian endometriosis patients and 36 healthy ...women.•Ten metabolites and 125 metabolite ratios were significantly altered in patients.•The best model provided sensitivity of 82.8%, specificity of 94.4%, and AUC of 94.4%.•Our data suggest the importance of these metabolites in pathophysiology of endometriosis.
Endometriosis is a complex, polygenic, and estrogen-dependent disease that affects 6% to 10% of women of reproductive age, and 30% to 50% of women with infertility and/or pelvic pain. Surgical diagnosis of endometriosis is still the gold standard, as there are currently no diagnostic biomarkers available. Due to the invasive diagnostics, it can take up to 11 years before affected women are diagnosed and receive the appropriate treatment. We performed a targeted metabolomics study to search for potential semi-invasive biomarkers in peritoneal fluid from endometriosis patients. Our case-control study comprised 29 ovarian endometriosis patients and 36 healthy control women. The 148 metabolites included acylcarnitines, glycerophospholipids, and sphingolipids, which were quantified by electrospray ionization tandem mass spectrometry. The strength of association between the metabolites and the metabolite ratios and disease was assessed using crude and adjusted odds ratios. The best combination of biomarkers was then selected by performing step-wise logistic regression. Our analysis reveals significantly decreased concentrations of 10 metabolites, of carnitine and acylcarnitines (C0, C8:1, C6C4:1 DC, C10:1), phosphatidylcholines (PC aa C38:3, PC aa C38:4, PC aa C40:4, PC aa C40:5), and sphingomyelins (SM C16:1, SM C18:1), and 125 significantly altered metabolite ratios in patients versus control women. The best model includes two ratios: a carnitine to a phosphatidylcholine (C0/PC ae C36:0); and between two phosphatidylcholines (PC aa C30:0/PC ae C32:2). When adjusted for age, this provides sensitivity of 82.8% and specificity of 94.4%, with AUC of 0.944. Our study supports the importance of carnitine, phosphatidylcholine, and sphingomyelin metabolites in the pathophysiology of endometriosis, and confirms the potential for the combination of individual metabolite ratios to provide biomarkers for semi-invasive diagnostics.
Endometriosis is a very common disease in pre-menopausal women, where defective metabolism of steroid hormones plays an important role in its development and promotion. In the present study, we have ...examined the expression of 11 estrogen and progesterone metabolizing enzymes and their corresponding receptors in samples of ovarian endometriomas and control endometrium. Expression analysis revealed significant up-regulation of enzymes involved in estradiol formation (aromatase, sulfatase and all reductive 17β-hydroxysteroid dehydrogenases) and in progesterone inactivation (AKR1C1 and AKR1C3). Among the estrogen and progesterone receptors, ERα was down-regulated, ERβ was up-regulated, and there was no significant difference in expression of progesterone receptors A and B (PRAB). Our data indicate that several enzymes of estrogen and progesterone metabolism are aberrantly expressed in endometriosis, which can lead to increased local levels of mitogenic estradiol and decreased levels of protective progesterone. Changes in estrogen receptor expression suggest that estradiol may also act via non-estrogen receptor-mediated pathways, while expression of progesterone receptors still needs further investigation.
DEEP INFILTRATING ENDOMETRIOSIS Martina Ribič-Pucelj
Zdravniški vestnik (Ljubljana, Slovenia : 1992),
02/2018, Letnik:
78
Journal Article
Recenzirano
Odprti dostop
Background: Endometriosis is not considered a unified disease, but a disease encompassing three differ- ent forms differentiated by aetiology and pathogenesis: peritoneal endometriosis, ovarian ...endometriosis and deep infiltrating endometriosis (DIE). The disease is classified as DIE when the lesions penetrate 5 mm or more into the retroperitoneal space. The estimated incidence of endometriosis in women of reproductive age ranges from 10–15 % and that of DIE from 3–10 %, the highest being in infertile women and in those with chronic pelvic pain. The leading symptoms of DIE are chronic pelvic pain which increases with age and correlates with the depth of infiltration and infertility. The most important diagnostic procedures are patient’s history and proper gynecological examination. The diagnosis is confirmed with laparoscopy. DIE can affect, beside reproductive organs, also bowel, bladder and ureters, therefore adi- tional diagnostic procedures must be performed preopertively to confirm or to exclude the involvement of the mentioned organs. Endometriosis is hormon dependent disease, there- fore several hormonal treatment regims are used to supress estrogen production but the symptoms recurr soon after caesation of the treatment. At the moment, surgical treatment with excision of all lesions, including those of bowel, bladder and ureters, is the method of choice but requires frequently interdisciplinary approach. Surgical treatment significantly reduces pain and improves fertility in inferile patients. Conclusions: DIE is not a rare form of endometriosis characterized by chronic pelvic pain and infertility. Medical treatment is not efficient. The method of choice is surgical treatment with excision of all lesions. It significantly reduces pelvic pain and enables high spontaneus and IVF preg- nacy rates.Therefore such patients should be treated at centres with experience in treatment of DIE and with possibility of interdisciplinary approach.
Endometriosis is defined as the presence of endometrial glands and stroma within extrauterine sites, and it is well known that endometriosis is an estrogen-dependent disease. The defective formation ...and metabolism of steroid hormones is responsible for the promotion and development of endometriosis. In the present study we examined the mRNA levels of six enzymes that are involved in the metabolism of estrogen and progesterone - aromatase, 17β-hydroxysteroid dehydrogenase (17β-HSD) types 1, 2 and 7, sulfatase and sulfotransferase - and of the steroid receptors - estrogen receptors α and β (ERα, ERβ) and progesterone receptors A and B (PRAB) - implicated in human ovarian endometriosis. We analyzed 16 samples of ovarian endometriosis and 9 of normal endometrium. The real-time polymerase chain reaction analyses revealed that six of the nine genes investigated are differentially regulated. Aromatase, 17β-HSD types 1 and 7, sulfatase and ERβ were statistically significantly upregulated, while ERα was significantly downregulated, in the endometriosis group compared with the control group. There were no significant differences in 17β-HSD type 2, sulfotransferase and PRAB gene expression. Our results indicate that, in addition to the previously reported upregulation of aromatase, upregulation of 17β-HSD types 1 and 7 and sulfatase can also increase the local estradiol concentration. This could thus be responsible for the estrogen-dependent growth of endometriotic tissue. Surprisingly ERα was downregulated.
Deep infiltrating endometriosis with colorectal involvement is a complex disorder, often requiring segmental bowel resection. Complete removal of all visible lesions is considered the adequate ...treatment of infiltrating endometriosis in order to reduce recurrence. In this article, we describe our experience with laparoscopic management of deep infiltrating endometriosis with involvement of the rectum.
A retrospective analysis of data from patients with deep infiltrating endometriosis with rectal involvement who underwent a laparoscopic surgery in the years 2002-2009 at the Department of Obstetrics and Gynecology at our institution was done.
Between 2002 and 2009, a laparoscopic partial rectal resection was performed in 52 patients, and laparoscopic disk resection was performed in 4 cases with deep infiltrating endometriosis. The mean age of patients was 34.4 years (range, 22-62 years). Preoperative symptoms included dysmenorrhea, dyspareunia, chronic pelvic pain, and infertility. The laparoscopic procedure was converted to formal laparotomy in 3 patients (5.4%). The mean duration of surgery was 145 minutes. Postoperative complications included 3 cases of anastomotic leakage with rectovaginal fistula in two cases and intraabdominal bleeding in 1 case. The mean hospital stay was 7 days. Postoperatively, nine patients had a normal delivery, two of them after in vitro fertilization treatment.
Laparoscopic rectal resection for deep infiltrating endometriosis is a relatively safe procedure, when performed by a surgeon and a gynecologist with sufficient experience in laparoscopic colorectal surgery.
► 78 out of 172 genes differentially expressed in ovarian endometriosis. ► 36 genes associate with terms signal peptide, extracellular region and secreted. ► 23 new estrogen-related genes associate ...with endometriosis. ► Differential expression of
ESR1,
ESR2,
PGR,
BGN confirmed by immunohistochemistry.
In the search for novel biomarkers of endometriosis, we selected 152 genes from the GeneLogic database based on results of genome-wide expression analysis of ovarian endometriosis, plus 20 genes related to estrogen metabolism and action. We then performed low-density array analysis of these 172 genes on 11 ovarian endometriosis samples and 9 control endometrium samples. Principal component analysis of the gene expression levels showed clear separation between the endometriosis and control groups. We identified 78 genes as differentially expressed. Based on Ingenuity pathway analysis, these differentially expressed genes were arranged into groups according to biological function. These analyses revealed that 32 differentially expressed genes are estrogen related, 23 of which have not been reported previously in connection with endometriosis. Functional annotation showed that 25 and 22 genes are associated with the biological terms “secreted” and “extracellular region”, respectively. Differential expression of 4 out of 5 genes related to estrogen metabolism and action (
ESR1,
ESR2,
PGR and
BGN) was also confirmed by immunohistochemistry. Our study thus reveals differential expression of several genes that have not previously been associated with endometriosis and that encode potential novel biomarkers and drug targets.
Background: Te purpose of the study was to determine the quality of life in patients with bowel endometriosis before and afer laparoscopic bowel resection.Material and methods: In the retrospective ...study we included 91 patients who underwent laparoscopic resection of the bowel affected by endometriosis at the Unit for Reproduction and the Unit for Gynecology, Department of Obstetrics and Gynecology Ljubljana, in the period from 2002 to 2011. Te study was retrospective. Te patients were sent a questionnaire regarding the symptoms before surgery and the effect of surgery on bowel symptoms, painful menstruation, painful sexual intercourse, chronic pelvic pain and quality of life before and afer surgery; 76 (83.5 %) patients replied to the questionnaire.Results: Before surgery, 72 (94.7 %) patients reported painful menstruation. Improvement or complete relief afer surgery was registered in 57 (79.1 %). Out of 60 (78.9 %) patients who had painful sexual intercourse before surgery, 49 (81.7 %) reported improvement or complete relief afer surgery. Bowel symptoms, present in 52 (68.4 %) patients before surgery, improved or completely disappeared in 48 (92.4 %) afer surgery. Chronic pelvic pain, present in 53 (69.7 %) before surgery, decreased or did not exist any more in 45 patients (86.5 %). Te quality of life before surgery was very poor in 32 patients (42.1 %), and poor in 21 patients (27.8 %). Afer the operation, the quality of life was reported as improved in 22 (28.9 %) and signifcantly improved in 42 (55.3 %).Conclusions: Laparoscopic bowel resection, indicated in extensive symptomatic endometriosis, signifcantly improves the patients’ quality of life.
Background: Te purpose of the study was to determine the quality of life in patients with bowel endometriosis before and afer laparoscopic bowel resection.Material and methods: In the retrospective ...study we included 91 patients who underwent laparoscopic resection of the bowel affected by endometriosis at the Unit for Reproduction and the Unit for Gynecology, Department of Obstetrics and Gynecology Ljubljana, in the period from 2002 to 2011. Te study was retrospective. Te patients were sent a questionnaire regarding the symptoms before surgery and the effect of surgery on bowel symptoms, painful menstruation, painful sexual intercourse, chronic pelvic pain and quality of life before and afer surgery; 76 (83.5 %) patients replied to the questionnaire.Results: Before surgery, 72 (94.7 %) patients reported painful menstruation. Improvement or complete relief afer surgery was registered in 57 (79.1 %). Out of 60 (78.9 %) patients who had painful sexual intercourse before surgery, 49 (81.7 %) reported improvement or complete relief afer surgery. Bowel symptoms, present in 52 (68.4 %) patients before surgery, improved or completely disappeared in 48 (92.4 %) afer surgery. Chronic pelvic pain, present in 53 (69.7 %) before surgery, decreased or did not exist any more in 45 patients (86.5 %). Te quality of life before surgery was very poor in 32 patients (42.1 %), and poor in 21 patients (27.8 %). Afer the operation, the quality of life was reported as improved in 22 (28.9 %) and signifcantly improved in 42 (55.3 %).Conclusions: Laparoscopic bowel resection, indicated in extensive symptomatic endometriosis, signifcantly improves the patients’ quality of life.
BackgroundThe aim of the research was to determine the success of laparoscopic myomectomy (LM), frequency of recurrence of fibroids following the treatment and possible risk factors for ...recurrence.MethodsRetrospective research was used. We included 455 females who underwent LM in the period from January 2003 until December 2006 at the Ljubljana Gynaecologic Clinic (Reproduction Clinical Department). The data was collected from the analysis of questionnaires sent to the females in 2010 to their postal addresses.ResultsThe questionnaire was completed by 297 (65.3 %) females, 6 questionnaires were excluded from further analysis due to incomplete answers. We analysed 291 questionnaries. The surgery fulfilled expectations of 257 (88.3%) females, uterine bleeding was normalised in 168 cases (85.3 %), pain was reduced or stopped completely in 135 cases (86.5 %). A fibroid recurred in 98 (33.7 %) cases, on average 25.1 (2-96) months after the procedure, 40 (40.8 %) females underwent repeat surgery. As for risk factors for fibroid recurrence following LM, the number of removed fibroids proved to be statistically significant (p = 0.026), while the impact of age was not statistically significant (p = 0.77).Conclusions Given that the probability of fibroid recurrence and repeat surgery increases with the number of removed fibroids in the first operation, it may be appropriate for women with multiple fibroids who have completed their fertility period to propose one of the methods of hysterectomy, in particular, are increasingly well-established minimally invasive laparoscopic supracervical or total hysterectomy.
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