Purpose Diet is a potentially modifiable risk factor for endometriosis. It has been hypothesized that vitamins C, E, and the B vitamins may influence factors involved in the pathogenesis of endometriosis, such as oxidative stress and steroid hormone metabolism. In this large, prospective cohort study, we examined the relation between intake of vitamins C, E, the B vitamins, and the use of multivitamin supplements and diagnosis of endometriosis. Methods Data were collected from women in the Nurses' Health Study II between 1991 and 2005. Diet was assessed via food frequency questionnaire. Incidence rate ratios (RR) and 95% confidence intervals (CI) were estimated using time-varying Cox proportional hazards models. Results A total of 1383 incident cases of laparoscopically-confirmed endometriosis were observed among 70,617 women during 735,286 person years of follow-up. Intakes of thiamine (B1) (RR = 0.84, CI = 0.72-0.99; P-value, test for linear trend[P] = 0.04), folate (B9) (RR = 0.79, CI = 0.66-0.93; P = 0.003), vitamin C (RR = 0.81, CI = 0.68-0.95; P = 0.02), and vitamin E (RR = 0.70, CI = 0.59-0.83; P<0.0001) solely from food sources were inversely related to endometriosis diagnosis. However, intakes of these nutrients from supplements alone were unrelated to endometriosis. Conclusion Thiamine, folate, vitamin C, and vitamin E from food sources are inversely related to endometriosis risk. Our results suggest that the protective mechanism may not be related to the nutrients themselves but rather other components of foods rich in these micronutrients or factors correlated with diets high in these vitamin-rich foods.
Purpose To compare pain symptoms and quality of life between epiphenomenon and endometriosis disease. Methods Between January 2004 and July 2008, 536 new cases of endometriosis confirmed by surgical biopsy were included in this observational cohort study (Auvergne Regional Cohort of Endometriosis). Questionnaires and visual analog scale scores for dysmenorrhoea, dyspareunia, chronic pelvic pain, premenstrual dysuria and dyschesia, quality of life instruments (SF-36), and sexual activity questionnaires were compared between group A (epiphenomenon group: 119 patients) and group B (endometriosis disease group: 318 patients with deep ovarian endometrioma and/or deep infiltrating nodules). Primary outcome was patient-reported pain rates. Secondary outcomes included quality-of-life tools. Results In cases of severe endometriosis, more pain at defecation and more dysmenorrhoea were observed than in cases of minimal endometriosis. The social repercussions and deterioration in quality of life were also affected, without any distinction between group A and B except for physical limitations. Quality of sex life was also affected in both groups. Conculsions This study confirms the ubiquitous pain symptoms of endometriosis. The lack of any correlation between functional symptomatology and anatomic severity of disease underlines how important it is not to neglect patients presenting what is called “minimal” endometriosis.
Purpose: Endometriosis may influence different aspects of reproductive physiology including folliculogenesis, ovulation, embryo quality, and fertilization. Recent data demonstrate that patients with endometriosis-associated infertility undergoing in vitro fertilization (IVF) have a reduction of pregnancy rates compared to women with other indications for IVF. The aim of the study is to evaluate the outcomes of IVF after controlled ovarian hyperstimulation (COH) with GnRH antagonist (GnRH-ant) or GnRH agonist (GnRH-a) in severe endometriosis patients.Methods: A total of 101 patients with severe endometriosis undergoing IVF cycles were retrospectively enrolled into two groups in relation to hypothalamic inhibition before COH, obtained respectively with leuprorelin and cetrorelix. We evaluated characteristics of COH and clinical outcomes (overall pregnancy rate, implantation rate, spontaneous miscarriages, ectopic pregnancies, and clinical pregnancy rates).Results: The group treated with GnRH-ant presented a similar number of MII oocytes and good quality embryos while using a lower amount of gonadotropins. Outcomes of COH with both GnRH-ant and GnRH-a were similar in patients with stage III-IV endometriosis. The number of retrieved oocytes, the number of obtained embryos, the implantation rates, and the clinical pregnancy rates were similar with GnRH-ant and GnRH-a protocols.Conclusions: Considering the pregnancy outcomes, COH with both GnRH-ant and GnRH-a protocols do not present statistical differences in patients with severe endometriosis, but the GnRH-ant protocol could be more convenient in term of gonadotropins amount and patient discomfort.
Purpose Perineal endometriosis is a rare disease characterized by the presence of ectopic endometrial stroma and glands in the perineum. Most commonly observed in the episiotomy scar after normal vaginal deliveries, perineal endometriosis is not often considered in the differential diagnosis of perineal masses. This could lead to unnecessary investigations and inadequate patient treatments. Case Report A 41-year-old woman complains of a tender perineal mass, which becomes hard and more painful during menses. Her symptoms started five years prior in the same area where a midline episiotomy was performed during a normal vaginal delivery. Complete surgical excision of the perineal mass was performed and the pathology report confirmed perineal endometriosis. No recurrence was noted on the postoperative course. Conclusion A comprehensive history and meticulous pelvic examination are essential in diagnosing perineal endometriosis. Surgical intervention is the best approach for treatment and permanent cure is usually achieved after complete excision of the perineal endometriosis.
Purpose The aim of our work was to explore which of the most commonly used pain scales is best suited to assess treatment success in endometriosis therapy and, therefore, qualifies best to be used as primary endpoint for clinical studies in this indication. Methods We compared patient's responses on the different pain scales Visual Analog Scale, Biberoglu and Behrman Score, and SF-36 Bodily Pain Subscale with the Clinical Global Impression score. Parametric and non-parametric correlation coefficients and effect sizes were calculated. Results A total of 428 patients with endometriosis-associated pelvic pain from three studies were included in our analyses. Their mean age was 31.4±6.3 years and their mean pain score on the visual analog scale was 58.1±21.9 at baseline. The highest correlation with the Clinical Global Impression score was observed for the visual analog scale followed by the B&B pelvic pain item. The highest effect sizes were found for dysmenorrhea and SF-36 bodily pain subscale followed by the visual analog scale. Conclusions A general measure of endometriosis-related pain can be recommended as primary endpoint in clinical trials to assess painful symptoms of endometriosis. In addition, a disease-specific quality of life tool is recommended to help interpret impact on patients’ daily activities.
Purpose The aim of this study is to assess post-operative complications, symptoms, patient satisfaction, and fertility outcome after a long-term follow-up period in patients with severe intestinal endometriosis. Methods In this retrospective study (January 1998 - December 2008) patients scheduled for a segmental colorectal resection by laparotomy were identified. Surgery was performed by a multidisciplinary team. Data were obtained from medical records and supplemented by a questionnaire. Results A total of 41 patients (median age 30 years [24–45]) were included with a mean follow-up of 50 months. Three patients were lost to follow-up. Chronic pelvic pain, dysmenorrhea, dyschezia, hematochezia, constipation, pencil like stool, diarrhea, and tenesmus decreased, respectively, in 24, 16, 31, 25, 26, 12, 11, and 21 patients. Post-operatively, one patient conceived naturally and eleven out of fifteen patients conceived after in vitro fertilization. The post-operative patient satisfaction rate (mean 7.4) was significantly higher compared to prior to surgery (mean 4.6). Four major complications were reported in the first year after surgery. The cumulative complication rate was 12%. Conclusions Segmental colorectal resection by laparotomy in patients with severe intestinal endometriosis effectively reduces symptoms and increases patient satisfaction with an acceptable risk on treatable complications.
Endometriosis is a chronic condition characterized by growth of endometrial tissue outside the uterus. Common symptoms include dysmenorrhoea, dyspareunia, non-cyclic pelvic pain, and infertility. Endometriosis is often treated surgically upon diagnosis but with a higher rate of recurrence, suggesting that a combination of surgical and medical management might provide better outcomes. The primary goal of medical treatment is to interrupt the growth and activity of endometriosis lesions. Because of the chronic nature of this disease, long-term or repeated courses of medication may be required to control symptoms. Increasing knowledge about the pathogenesis of endometriosis at the cellular and molecular levels may give us the opportunity to use new pharmaceutical agents affecting angiogenesis, inflammation, oxidative stress, proliferation or apoptosis to prevent or inhibit the development of endometriosis.
Purpose Iron and copper disruption in endometriosis among infertile women has been investigated. Their role in the pathogenesis of endometriosis has also been studied. Methods Blood and peritoneal fluid samples were collected from women undergoing laparoscopy. The studied group included 24 infertile women with endometriosis, while 14 women with unexplained infertility represented the control group. Results Iron and copper concentrations were estimated. Serum iron levels were significantly lower in infertile endometriotic women compared to the control group. On the other hand, its levels were significantly higher in the peritoneal fluid of infertile endometriotic women than those in controls when they were put side by side. Copper levels were significantly lower in the peritoneal fluid of infertile endometriotic women when measured up to controls. However, there was no significant difference in serum copper levels between the two groups. Conculsions Oxidative stress secondary to elevated peritoneal fluid iron, or deficiency of peritoneal copper might play a role in the development and progression of endometriosis, and its related infertility.
Purpose: Laparoscopy is a very accurate diagnostic tool for endometriosis. However, diagnostic accuracy has been questioned, as there is no reliable link between the visual status of the peritoneal cavity reported by laparoscopy and the patient's clinical condition. In addition, there is no actual association between the presence of typical peritoneal lesions and its confirmation by means of pathologic examination. The aim of our study was to determine whether histologic microscopic assessment is a reliable method for the diagnosis of endometriosis.Methods: We performed a prospective transversal study with 68 women with suggestive history of endometriosis who underwent laparoscopy. After biopsy, an intra-observer and inter-observer variability of the histologic study was analyzed by the Kappa integrity test to reveal whether microscopic examination is an accurate exam for the diagnosis of endometriosis.Results: In 38 of the 68 slides, all examiners confirmed the presence of endometriosis (55.9%). The intra- observer analysis showed an individual agreement degree over 92 (kappa=0.85; P<.001), and the inter - observer analysis showed an overall agreement of 76.5 (k=0.78; P<.001). Conclusions: The results showed a high level of integrity of the histologic exam for the diagnosis of endometriosis and confirmed that microscopic histology is a reliable and reproducible diagnostic tool for endometriosis.
Purpose: To compare pain symptoms and quality of life between epiphenomenon and endometriosis disease.Methods: Between January 2004 and July 2008, 536 new cases of endometriosis confirmed by surgical biopsy were included in this observational cohort study (Auvergne Regional Cohort of Endometriosis). Questionnaires and visual analog scale scores for dysmenorrhoea, dyspareunia, chronic pelvic pain, premenstrual dysuria and dyschesia, quality of life instruments (SF-36), and sexual activity questionnaires were compared between group A (epiphenomenon group: 119 patients) and group B (endometriosis disease group: 318 patients with deep ovarian endometrioma and/or deep infiltrating nodules). Primary outcome was patient-reported pain rates. Secondary outcomes included quality-of-life tools.Results: In cases of severe endometriosis, more pain at defecation and more dysmenorrhoea were observed than in cases of minimal endometriosis.The social repercussions and deterioration in quality of life were also affected, without any distinction between group A and B except for physical limitations. Quality of sex life was also affected in both groups.Conclusions: This study confirms the ubiquitous pain symptoms of endometriosis. The lack of any correlation between functional symptomatology and anatomic severity of disease underlines how important it is not to neglect patients presenting what is called "minimal" endometriosis.
Purpose: To investigate expression of molecular transporters and CYP4B1 in endometrium from women with and without endometriosis.Methods: Expression of genes encoding proteins: ATP-binding cassette sub-family G member 1 (ABCG1), aquaporin 3 (AQP3), solute carrier family 16, member 6 (monocarboxylic acid transporter 7) (SLC16A6), and transmembrane emp24 protein transport domain containing 6 (TMED6), as well as a member of the cytochrome P450 family 4 subfamily B, polypeptide 1 (CYP4B1) were assessed by quantitative (Q) RT-PCR in proliferative (PE) and early secretory (ESE) endometrium from 27 normo-ovulatory women with and without endometriosis. Cellular localization of these proteins was determined by immunohistochemistry.Results: In eutopic endometrial tissue from women without endometriosis, mRNA expression of ABCG1, CYP4B1, and SLC16A6 was significantly up-regulated in the PE to ESE transition. CYP4B1 mRNA in endometrium from women with disease increased significantly compared to samples from women without disease, while there was no change in ABCG1 and SLC16A6 mRNA levels. However, immunodetection of ABCG1, AQP3, and TMED6 was similar across cycle phases, and there was no significant difference in immunostaining intensity or localization between women with and without endometriosis.Conclusions: Molecular transporters and CYP4B1 are expressed in human endometrium, and a role for transporters and CYP4B1 in normal endometrial function and in women with endometriosis remains to be determined.
Background Giant endometriomas are a rare condition and the association with cystadenomas has not been reported previously. Case A 37-year-old woman without any previous medical history of disease presented to the emergency department because of dyspnea. During physical examination the patient presented a considerably sized abdominal growth when a tomography was performed; this revealed a large mass which was presumably dependent on the pelvic cavity. Surgery was performed to remove the tumor, during which another cyst was found in the contra-lateral ovary. Conculsions The histopathologic report showed that the tumor found on the left ovary corresponded to a giant endometriosic cyst and on the right ovary, a papillary serous cystadenoma.
Purpose: Endometriosis of the umbilicus is rare, with the most common site being laparoscopy scars. We report here a case of spontaneously developed, solitary umbilical endometriosis, not associated with a surgical scar, that was successfully treated with local excision.Case: A 44-year-old Japanese woman was admitted complaining of an umbilical mass with cyclic pain, associated with her menstrual cycle. She had noticed the umbilical pain six months earlier. She had not received an abdominal operation or hormonal treatment. Abdominal examination revealed an index-finger-tip-sized, dome-shaped, painful, subcutaneous mass beneath the umbilicus with slightly brownish skin. Gynecologic examination showed a fibroid uterus of double-fist size. Magnetic resonance imaging revealed a subcutaneous mass beneath the umbilicus 1.5 cm in diameter. The umbilical mass was revealed to be high intensity with a small low-intensity area by both T1-weighted and T2-weighted images, suggesting umbilical endometriosis. The patient was treated by local excision of the umbilical mass, and full excision was achieved. Total hysterectomy and right salpingo-oophorectomy were performed simultaneously to treat the uterine fibroid. The pathologic diagnosis of the excised umbilical tissue was endometriosis. Endometriotic or adenomyotic lesion was not detected in the resected uterine and tubo-ovarian tissues. Gonadotropin-releasing hormone antagonist administration for six months was commenced after the surgical treatment. The patient is doing well without evidence of disease four months after surgery.Conclusion: Spontaneously developed umbilical endometriosis is rare. Simultaneous laparoscopy or laparotomy should be considered to assess co-existent pelvic endometriosis at the time of surgical treatment in selected cases.
Micro RNAs (miRNAs) are small non-coding RNAs which regulate numerous cellular processes at the posttranscriptional and translational level. In endometriosis, expression of miRNAs is frequently dysregulated. miRNAs are predicted to modulate several relevant processes involved in the pathogenesis of endometriosis, including cell proliferation, apoptosis, cell migration and invasiveness, angiogenesis, and inflammation, as well as stem cell properties. miRNA expression has been studied by microarray profiling and quantitative real-time PCR, enabling the identification of specific miRNAs as potential novel diagnostic markers for endometriosis. The future application of locked-nucleic acid miRNA inhibitors, miRNA decoys, and synergistic approaches involving conventional therapeutics may open up promising new perspectives in endometriosis therapy.
Purpose Ectopic implantation of endometrium leading to endometriosis has been correlated with various immune and non-immune parameters. Inflammatory cytokines including IL-2, IFN-γ, TNF-α, increase in serum and peritoneal fluid of endometriotic patients, while elevated levels of prostaglandins PGE1 and PGE2 have been accused of facilitating the inflammation process. Using the experimental model of L-carnitine (L-Cn)-induced endometriosis, the aim of this study was to explore the role of PGE1 and PGE2 in endometriosis development and define whether L-Cn had a direct effect on endometrial cells. Methods During treatment with L-Cn, experimental mice were injected with indomethacin or specific PGE1 and PGE2 analogs and their effect on the L-Cn-induced inflammatory state was examined. Primary uterine cells or human endometrial adenocarcinoma cell lines were used to assess the direct or indirect effect of L-Cn. Results The seven-day treatment of virgin females with L-Cn induced obvious endometrial abnormalities with accumulation of CD90 and CD11 cells. Administration of indomethacin alleviated some of the L-Cn-induced effects, but could not inverse the phenotype. Interestingly, 11-deoxy-PGE1 aggravated the L-Cn-induced effects, whereas 17-phenyl-trimor-PGE2 reversed them. In vitro experiments showed that the effect of L-Cn depended on the nature of endometrioma cells. L-Cn could aggravate the inflammatory state of Ishikawa-inoculated mice, but could alleviate symptoms from MFE-319 inoculated females. Conculsions Although PGE2 appeared to play a key role in the L-Cn-induced uterus inflammation, the actual role of L-Cn depends on the nature of endometrioma cells and can aggravate or protect from inflammation according to the induced regulatory pathways.
Purpose This study was performed to assess the apoptotic index and Bcl-2 expression in ectopic endometrium of patients with endometriosis and in eutopic endometrium of patients without endometriosis, according to the phase of the menstrual cycle. Methods A total of eight patients with endometriosis and in eutopic endometrium of eight patients without endometriosis, according to the phase of the menstrual cycle. Samples were collected during surgical procedures and histologic sections were stained with hematoxylin-eosin and underwent morphometric analysis for assessment of the apoptotic index. TUNEL immunohistochemical assay was performed to validate the morphologic criteria used for quantification of apoptosis. Results The apoptotic index was significantly lower in the ectopic endometrium of patients with endometriosis in comparison to the eutopic endometrium of patients without endometriosis, regardless of the menstrual cycle phase. No statistically significant difference in endometrial Bcl-2 expression was observed among patients with and without endometriosis. Conclusions We conclude that ectopic endometrial tissues from women with endometriosis are less susceptible to apoptosis and these cells demonstrate an increased ability to survive and higher chances to colonize and grow in ectopic sites - important factors in the pathogenesis of endometriosis.
Purpose: A comprehensive assessment of gynecologic, general, and gastrointestinal complaints of a group of women with laparoscopically confirmed endometriosis compared to another group of women without endometriosis was performed. The possibility of dietary intolerance in relation to the coexistence of endometriosis was also assessed.Methods: This was a prospective, comparative study conducted on 57 patients who had had laparoscopies for various gynecologic complaints. These women were recruited sequentially into the study so as to avoid selection bias (age range 20 to 55). Twenty-three patients were diagnosed with endometriosis while the other 34 did not have this pathology. Prior to laparoscopy these patients were asked through a telephone questionnaire about associated long-term gastrointestinal symptoms, dietary intolerance, and general and gynecologic symptoms.Results: Twenty-three women were diagnosed as having pelvic endometriosis. The remaining thirtyfour patients were noted to suffer from pathology other than endometriosis. Gastro-intestinal symptoms such as dyspepsia (P<. 01) and diarrhea (P<.05) were significantly more common in the endometriosis group compared to the other group of women. Women with endometriosis complained of more gastrointestinal symptoms (53% vs. 31%) and food intolerance (26% vs. 14%) than the women without endometriosis. These differences between both groups did not attain statistical significance possibly because the study was not suitably powered to reveal this. No significant differences were noted for most of the other aggregated gynecologic and general symptoms except for shorter menstrual cycles (P<. 01) and depression (P<. 05) in the women diagnosed with endometriosis.Conclusions: Patients suffering from endometriosis in this study complained of significantly more gastrointestinal symptoms. A nonsignificant trend of dietary intolerance was noted in the women shown to suffer from endometriosis. These findings may shed some light on the pathogenesis and the management of endometriosis.
Purpose Intestinal bowel endometriosis is reported in up to 37% of women with proven endometriosis. The aim of this study was to evaluate by colonoscopy and magnetic resonance imaging, patients suspected of deep infiltrating endometriosis (DIE) including the bowel wall that presented with cyclic hematochezia. Methods Twenty-four patients with cyclic hematochezia were retrospectively analyzed on colonoscopic features of colonoscopy, corresponding biopsy data, and outcome of magnetic resonance imaging evaluation. Fifteen out of 24 patients underwent bowel resection because of insufficient response to hormonal treatment (N=14) or obstructive ileus (N=1). Outcome of surgery and histologic examination of the resected specimens were evaluated. Results Colonoscopy proved intestinal endometriosis in only one out of 24 (4%) patients with cyclic hematochezia. In 13 out of 15 bowel resections endometriosis was found at histopathology. The location and dimension of lesions during surgery correlated well with magnetic resonance imaging findings. However, magnetic resonance imaging revealed a limited capacity to detect luminal narrowing of the bowel. Conclusions This study shows that colonoscopic findings of bowel endometriosis are aspecific. Colonoscopy, an invasive investigation, should therefore not be performed to diagnose endometriosis infiltrating the bowel wall. Magnetic resonance imaging provides good diagnostic work-up and in selected patients a roadmap to surgery.
Aim Macrophage migration inhibitory factor (MIF) is a cytokine whose expression is elevated in endometriotic tissue from women with the disease but the functional role of this factor in the pathogenesis of the disease is uncertain. The objective of the current study was to examine the role of MIF in the pathogenesis of endometriosis. Method Experimental endometriosis was induced in mice and the ability of the MIF antagonist, ISO-1, to reduce endometriotic implant size was assessed. Results Administration of ISO-1 resulted in a significant reduction in implant size and vascularity (as assessed by Flk1 mRNA expression) which was not associated with an alteration in the reproductive cycle. Conclusion These data suggest that inhibition of MIF activity is associated with a significant reduction in endometriotic implant size and leads us to speculate that a similar approach of targeting MIF may prove useful in treating endometriosis in humans.
