Fertil Steril. 2009 Apr;91(4 Suppl):1608-10. Epub 2009 Jan 7.

 

Peritoneal ectopic lesions from women with endometriosis show abnormalities in progesterone-dependent glycan expression.

Jones CJ, Nardo LG, Litta P, Fazleabas AT.

Maternal and Fetal Health Research Centre, School of Clinical and Laboratory Science, University of Manchester, Manchester, United Kingdom. carolyn.jones@manchester.ac.uk

Examination of 12 paired peritoneal ectopic and eutopic endometria for histochemical binding of Dolichos biflorus agglutinin, normally found in the mid-late secretory part of the cycle, showed a failure of lectin binding in 9 of 11 secretory-phase lesions although the eutopic specimens generally stained normally. This failure of glycan expression in the secretory phase may result from various anomalies, including an inability to respond to progesterone, possibly due to a lack of, or to nonfunctional, progesterone receptors, suggesting that an ectopic environment may produce changes in tissue cell biology and hormonal responsiveness compared with that of eutopic endometrium.

Publication Types:

J Steroid Biochem Mol Biol. 2009 Jan;113(1-2):105-15. Epub 2008 Dec 14.

 

Global gene expression profiling of progesterone receptor modulators in T47D cells provides a new classification system.

Afhüppe W, Sommer A, Müller J, Schwede W, Fuhrmann U, Möller C.

Bayer Schering Pharma AG, TRG Women’s Healthcare, Müllerstr. 178, D-13342 Berlin, Germany.

Progesterone receptor modulators (PRMs) play an important role in women’s health. They are widely used in oral contraception or hormone therapy, and provide an attractive treatment approach for gynecological disorders such as uterine leiomyomas, endometriosis or breast cancer. Due to the broad range of activities, various studies were conducted to assess progesterone receptor antagonists (PAs) and selective progesterone receptor modulators (SPRMs) with respect to progesterone receptor (PR) agonistic and antagonistic activities in vivo. These properties are not always adequately reflected in classical in vitro models, especially differences in the agonistic potential of SPRMs, such as asoprisnil, J1042, and J912, and mixed antagonists, such as mifepristone, are not sufficiently substantiated. The effects of PRMs upon gene expression in progesterone target tissues such as breast epithelium and uterus are poorly understood. This study compares the properties of PR ligands using mammalian two-hybrid assays and gene expression profiling. The protein-protein interaction analyses in HeLa cells provide for specific ligand-induced PR conformations, whereas Affymetrix GeneChip HG-U133Plus2.0 analyses in T47D breast cancer cells indicate the transcriptional activity on the level of target genes. The analyses comprise the pure agonist R5020, the non-steroidal PR modulator PRA-910, SPRMs (J1042, asoprisnil, J912), the mixed antagonist mifepristone, classical antagonists (onapristone, ZK 137316) and the pure antagonist lonaprisan to consider all types of ligands described before. Marginal differences were identified in coactivator interaction profiles at all, but significant differences between SPRMs and PR antagonists (PAs) were observed in recruiting the LXXLL-motif containing peptide (LX-H10), very similar to in vivo activities in endometrial transformation in the rabbit (McPhail test). Global gene expression profiles demonstrated progesterone-independent effects for all PR modulators examined and emphasised similarities of asoprisnil and J1042 compared to J912 and all types of PR antagonists. In summary, the data support the popular concept of PR modulator classification in agonists, selective progesterone receptor modulators, mixed and pure antagonists. It further refines previous classification models and accentuates unique effects for each PR modulator.

Reproduction. 2009 Apr;137(4):727-37. Epub 2009 Jan 7.

 

Nuclear factor kappaB pathway and interleukin-6 are affected in eutopic endometrium of women with endometriosis.

Ponce C, Torres M, Galleguillos C, Sovino H, Boric MA, Fuentes A, Johnson MC.

School of Medicine, Institute of Maternal and Child Research San Borja Arriarán Clinical Hospital, University of Chile, Santiago, Chile.

In order to investigate the role of the nuclear factor kappaB (NFKB) pathway on gene expression in the eutopic endometrium in endometriosis, and in particular of interleukin-6 (IL6), we evaluated RELA, IkappaB kinase (CHUK), NFKBIA and IL6 expressions and NFKB DNA binding in eutopic endometrium from women with endometriosis. Eutopic endometrium was obtained from 37 women with endometriosis and 42 fertile women during laparoscopy. We analysed RELA, CHUK, NFKBIA and IL6 mRNA levels (RT-PCR); RELA, CHUK and NFKBIA proteins and p-NFKBIA/NFKBIA ratio (western blot); and NFKB binding (DNA shift assay) and IL6 concentration (ELISA) in endometrial explants. Our results indicate that mRNA and cytoplasmic proteins of RELA and CHUK exhibit constant levels in normal endometrium during the menstrual cycle. A dramatic increase (P<0.05) in NFKBIA mRNA expression, RELA nuclear presence and the mRNA and the protein of IL6 during late secretory phase was also observed in this tissue. By contrast, in eutopic endometrium from endometriosis patients, a decrease (P<0.05) in IL6 mRNA and protein (61%), NFKBIA mRNA (46%), p-NFKBIA/NFKBIA ratio (42%), RELA nuclear stromal (68%) and CHUK (48%) proteins were found exclusively during the late secretory phase compared with normal endometrium. In conclusion, the canonical activation of NFKB pathway is deregulated and may have reduced transcriptional function affecting NFKBIA and IL6 expression, genes related local proinflammatory processes. These molecular alterations observed during the late secretory phase in eutopic endometrium from endometriosis patients constitute a NFKB system dysfunction, suggesting that NFKB could be an important factor in endometriosis aetiology.

Publication Types:

Gynecol Obstet Fertil. 2009 Jan;37(1):57-69. Epub 2009 Jan 6.

 

Republished from:

Endometriosis and pelvic pain: epidemiological evidence of the relationship and implications

[Article in French]

Fauconnier A, Fritel X, Chapron C.

Unité 149 recherches épidémiologiques en santé périnatale et santé des femmes, Inserm, Paris, France. afauconnier@chi-poissy-st-germain.fr

The relationship between chronic pelvic pain symptoms and endometriosis is unclear because painful symptoms are frequent in women without this pathology, and because asymptomatic forms of endometriosis exist. Our comprehensive review attempts to clarify the links between the characteristics of lesions and the semiology of chronic pelvic pain symptoms. Based on randomized trials against placebo, endometriosis appears to be responsible for chronic pelvic pain symptoms in more than half of confirmed cases. A causal association between severe dysmenorrhoea and endometriosis is very probable. This association is independent of the macroscopic type of the lesions or their anatomical locations and may be related to recurrent cyclic microbleeding in the implants. Endometriosis-related adhesions may also cause severe dysmenorrhoea. There are histological and physiopathological arguments for the responsibility of deeply infiltrating endometriosis (DIE) in severe chronic pelvic pain symptoms. DIE-related pain may be in relation with compression or infiltration of nerves in the subperitoneal pelvic space by the implants. The painful symptoms caused by DIE present particular characteristics, being specific to involvement of precise anatomical locations (severe deep dyspareunia, painful defecation) or organs (functional urinary tract signs, bowel signs). They can thus be described as “location indicating pain”. A precise semiological analysis of the chronic pelvic pain symptoms characteristics is useful for the diagnosis and therapeutic.

Publication Types:

Gynecol Obstet Invest. 2009;67(3):195-201. Epub 2008 Dec 20.

 

Alterations in RCAS1 serum concentration levels during menstrual cycle in patients with uterine leiomyoma and lack of analogical changes in adenomyosis.

Wicherek L.

Department of Gynecology, Obstetrics and Oncology, The Jagiellonian University, Krakow, Poland. mowicher@cyf-kr.edu.pl

INTRODUCTION: The selective suppression phenomenon of the cytotoxic immune response occurs in the endometrium at the beginning of decidualization. This process seems to be associated with an increase in the endometrial expression of proteins such as RCAS1 that are involved in the suppression of immune cell activity. The aim of the present study was to evaluate alterations in the RCAS1 blood serum concentration levels in women with uterine leiomyoma over the course of the different menstrual cycle phases and to compare these levels with those found in patients suffering from adenomyosis. MATERIAL AND METHODS: The sRCAS1 blood serum concentration level was determined for 87 patients, including 38 patients with both adenomyosis and uterine leiomyoma, and 49 suffering from leiomyomatosis alone. RESULTS: Fluctuations in sRCAS1 blood serum concentration levels correlating with the menstrual cycle phases were demonstrated in patients suffering from uterine leiomyoma alone. The highest level of sRCAS1 concentration was found during the secretory cycle phase and the lowest during the proliferative cycle phase. However, no such fluctuations correlating with menstrual cycle phases were observed in patients suffering from both adenomyosis and leiomyoma. In fact, the level of sRCAS1 blood serum concentration in patients with adenomyosis remained almost constant. Patients with adenomyosis and leiomyoma were characterized by statistically significantly higher blood serum sRCAS1 levels during the proliferative cycle phase in comparison with the sRCAS1 blood serum levels in patients with leiomyoma alone. CONCLUSION:The lack of alterations in the sRCAS1 blood serum concentration levels observed in patients with adenomyosis may favor the development of the condition. Copyright 2008 S. Karger AG, Basel.

Publication Types:

Maturitas. 2009 Apr 20;62(4):338-42. Epub 2008 Dec 31.

 

Progestogen use in women approaching the menopause and breast cancer risk.

Campagnoli C, Ambroggio S, Lotano MR, Peris C.

Endocrinological Gynecology, Sant’Anna Gynecological Hospital, Corso Spezia 60, Turin, Italy. carlo.campagnoli@alice.it

OBJECTIVE: Progestogens, particularly synthetic progestins, are widely used to contrast the clinical consequences of the relative hyperestrogenism that characterizes the years preceding the menopause. As a large body of data on postmenopausal hormone therapy (HT) demonstrates that the addition of synthetic progestins to estrogen increases the breast cancer risk compared to estrogen alone, it is important to evaluate if the use of progestogens in premenopausal years is associated with the risk of breast cancer. METHODS: Main literature data on the association with breast cancer risk of progestogens, either used alone in premenopausal years or added to estrogen in postmenopausal HT, were reviewed. RESULTS: Available data suggest that long-term current use of progestogens in premenopausal women after the age of 40 years can increase the risk of breast cancer. Consistently with the data on postmenopausal HT, the risk increase is higher for lobular cancer than for ductal cancer. CONCLUSIONS: The most important and widely accepted indications to the use of progestogens in the years preceding the menopause are anovulatory menstrual disorders, for which a limited period of treatment is generally sufficient. Awaiting for further data, when using progestogens for longer periods to treat other problems (endometriosis, cyclical mastalgia, etc.), the possibility of increased breast cancer risk and clinical benefits have to be weighed. Anyway, as micronized progesterone and dydrogesterone, at least when they were used in postmenopausal HT, seem to have, according to a large observational study, a safer risk profile on the breast, the preferential use of these preparations could be suggested.

Publication Types:

Arch Gynecol Obstet. 2009 Aug;280(2):235-42. Epub 2008 Dec 31.

 

Clinical management and immunohistochemical analysis of umbilical endometriosis.

Mechsner S, Bartley J, Infanger M, Loddenkemper C, Herbel J, Ebert AD.

Department of Gynecology, Endometriosis Research Center Charité, Charité, Campus Benjamin Franklin, Berlin, Germany. sylvia.mechsner@charite.de

PURPOSE: To established a strategy for diagnostic and therapeutic management of umbilical endometriosis and to determine the biological character. METHODS: Clinical examination, vaginal and abdominal ultrasound, magnetic resonance imaging of the abdominal wall and laparoscopy were performed on a 42-year-old woman with umbilical endometriosis. Surgery with umbilical reconstruction was performed by a new plastic surgery technique. Immunohistochemical analyses (against Ki 67, estrogen/progestogen receptor, CD10, smooth muscle actin, desmin, caldesmon, von Willebrandt factor, cyclooxygensae-2 and VEGF) were done to characterize the umbilical endometriotic lesion. RESULTS: The extension of the endometriotic lesion necessitated total removal of the umbilicus. Umbilical reconstruction was performed by a new plastic surgery technique. The lesion did express CD10, estrogen and progestogen receptors, and did show a moderate proliferation rate. Furthermore, signs of metaplastic processes such as smooth muscle metaplasia and angiogenesis were detected. The endometriotic lesion was positive not only for smooth muscle actin, caldesmon and desmin, but also for COX-2 and VEGF. CONCLUSION: Based on a case report and a literature review, we discuss the diagnostic and therapeutic management of umbilical endometriosis at our endometriosis research center. Furthermore, our data suggest that the umbilical endometriotic lesion originated from reactivated multipotent cells.

Publication Types:

Med Sci Monit. 2009 Jan;15(1):CR1-4.

 

Efficacy of long-term, low-dose gonadotropin-releasing hormone agonist therapy (draw-back therapy) for adenomyosis.

Akira S, Mine K, Kuwabara Y, Takeshita T.

Department of Obstetrics and Gynecology, Nippon Medical School, Tokyo, Japan. s-akira@nms.ac.jp

BACKGROUND: The usefulness of long-term, low-dose gonadotropin-releasing hormone agonist (GnRHa; buserelin acetate) therapy, so-called draw-back therapy, for the treatment of adenomyosis was investigated not. MATERIAL/METHODS: A retrospective observational study was conducted covering the period between January 2003 and March 2008. The subjects consisted of 12 patients with adenomyosis who underwent draw-back therapy for 2 years and had previously received GnRHa. GnRHa was initiated at 900 microg/day (6 nasal sprays/day). When the CA-125 level normalized, the GnRHa dosage was adjusted to 150-750 microg/day to achieve a plasma estradiol (E2) concentration of 20-50 pg/ml (i.e., the therapeutic window). Pain during withdrawal bleeding and chronic pelvic pain were assessed using a visual analogue scale. In addition, bone mineral density (BMD) of the lumbar vertebrae was measured using dual-energy X-ray absorptiometry. RESULTS: The mean GnRHa dose during draw-back therapy was 435 microg/day (2.9 nasal sprays/day). The mean E2 level during draw-back therapy was 36.3+/-14.3 pg/ml. The intensity of chronic pelvic pain was significantly lower during draw-back therapy than before draw-back therapy, and was nearly eliminated in many patients (4.8+/-1.2 vs. 0.6+/-0.7, respectively [p=0.000]). Compared to the severity of vasomotor symptoms during previous regular GnRHa therapy, the severity of vasomotor symptoms during draw-back therapy was significantly lower (3.8+/-0.7 vs 1.1+/-0.7, respectively [p=0.000]). The decrease in BMD during a 6-month course of treatment was 0.96+/-0.9%. CONCLUSIONS: GnRHa draw-back therapy allowed maintenance of plasma E2 levels within the therapeutic window. GnRHa can thus be administered for long periods of time while maintaining therapeutic effects on adenomyosis and suppressing adverse events.

Arch Gynecol Obstet. 2009 Aug;280(2):195-9. Epub 2008 Dec 27.

 

Apoptosis patterns in eutopic and ectopic endometrium, adhesions and normal-looking peritoneum from women with or without endometriosis.

Hassa H, Tanir HM, Tekin B, Artan S, Dundar E, Kirilmaz SD, Sahin Mutlu F.

Department of Obstetrics and Gynecology, Eskisehir Osmangazi University School of Medicine, Meselik Kampusu, Eskisehir, Turkey.

OBJECTIVE: To assess the apoptosis rate in eutopic and ectopic endometrial stromal and glandular cells, normal peritoneum and adhesions in women with endometriosis. METHODS: A total number of 97 women with (n:60) and without (n:37) histopathologically confirmed endometriosis who underwent laparoscopy or laparotomy in the early follicular phase of the menstrual cycles for pain and infertility were included in this study. Stage I/II and stage III/IV were categorized as early staged and late-staged endometriosis. The endometrial samples were obtained with a Novack cannula from the corpus of the uterus. Normal-looking peritoneum, peritoneal implants and adhesions were sampled and fixed in formaldehyde for immunohistochemical staining with Bcl-2 and Bax. Tissue samples were fixed in formaldehyde for the assessment of apoptosis via terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL) and M30 cytoDEATH antibody. RESULTS: The intensity of Bax staining of normal-looking peritoneum in early staged endometriosis was higher, compared to women with late-staged and women without endometriosis (P = 0.03). However, degree of Bcl-2 staining did not differ among early and late-staged endometriosis and women without endometriosis (P = 0.1). In terms of Bcl-2 and Bax staining in the stromal and glandular parts of the eutopic endometria, no significant differences were detected among three groups. In cases with early- and late-staged endometriosis the intensity of Bax and Bcl-2 stainings did not differ in both stromal and glandular parts of ectopic endometria. Number of cells with positive apoptotic signals assessed via TUNEL (P = 1.0) and M30 cytoDEATH antibody (P = 0.59) in normal-looking peritoneum did not differ between three groups. In addition, no difference in term of numbers of apoptotic cells obtained from adhesions was observed between three groups (for TUNEL, P = 0.29, for M30, P = 0.19). CONCLUSIONS: Apoptosis patterns did not differ in the eutopic and ectopic endometria as well as adhesions of women with or without endometriosis.

J Minim Invasive Gynecol. 2009 Jan-Feb;16(1):95-7.

 

Comment in:

Isolated extrapelvic endometriosis of the gluteal muscle.

Guida M, Greco E, Di Spiezio Sardo A, Borriello M, Morra I, Nappi C.

Department of Gynecology and Obstetrics, University of Naples Federico II, Naples, Italy.

A 33-year-old woman with a 2-year history of swelling and pain in her buttock and left thigh fluctuating with her menstrual cycle who was becoming progressively disabled was referred to the department of orthopedics. Magnetic resonance imaging (MRI) detected a left buttock lesion of 3 x 2 cm that was initially diagnosed as muscular-fiber laceration with associated hematoma. The worsening of her symptomatology required an ultrasound-guided biopsy of the lesion that revealed endometriosis. Laparoscopy showed the pelvis to be free of gross disease. Hormonal suppression by means of gonadotropin-releasing hormone analog therapy proved adequate in temporarily alleviating symptoms. A year later the patient underwent surgical excision of the buttock lesion, which was effective in alleviating her symptoms for a short period of 10 months. A 1-year follow-up MRI revealed several small endometriotic foci, located among piriformis and obturator internus muscle fibers, which were considered not suitable for surgical removal. The patient is currently on a drug regime for pain management. However, she has experienced permanent muscular damage on her left buttock including significant omolateral gluteus strength reduction, functional impairment (inability to rotate laterally or bend her left leg), and the assumption of an antalgic gait while walking. Because of impairment in her deambulation capability, total physical invalidity was agreed for her by the National Health Care Services.

Publication Types:

Br J Radiol. 2009 Jan;82(973):e20-2.

 

Clear cell adenocarcinoma of the uterine cervix arising from a background of cervical endometriosis.

Hiromura T, Tanaka YO, Nishioka T, Satoh M, Tomita K.

 

Department of Radiology, NTT East Corp. Sapporo Hospital, Sapporo 060-0061, Japan. thrmr@amber.plala.or.jp

The radiological findings of cervical clear cell adenocarcinoma (CCA) have not been described previously. Here, we present MR findings of this neoplasm that included mixed solid and cystic components with eccentric solid components. These are similar to the MR features of ovarian CCA. Endometriosis was also noted in the uterine cervix. Coexistence of CCA and endometriosis at the cervix suggests that the pathogenesis may be similar to that of ovarian CCA.

Publication Types:

Hum Reprod. 2009 Mar;24(3):602-7. Epub 2008 Dec 17.

 

Comment in:

Preoperative work-up for patients with deeply infiltrating endometriosis: transvaginal ultrasonography must definitely be the first-line imaging examination.

Piketty M, Chopin N, Dousset B, Millischer-Bellaische AE, Roseau G, Leconte M, Borghese B, Chapron C.

Department of Gynecology, Obstetrics II and Reproductive Medicine, Université Paris Descartes, Paris, France.

BACKGROUND: Transvaginal ultrasonography (TVUS) has important advantages compared with transrectal ultrasonography (TRUS): it is less invasive, is cost-effective, is a familiar and well-accepted approach, and anesthesia is not required. We compared the accuracy of TVUS and TRUS for diagnosing rectal wall involvement in patients presenting with histologically proved deeply infiltrating endometriosis (DIE). METHODS: Prospective study of 134 patients with histologically proved DIE underwent preoperative investigations using both TVUS and TRUS. The radiologist (TVUS) and sonographer (TRUS) were unaware of the clinical findings but knew that DIE was suspected. RESULTS: DIE was confirmed histologically for all the patients. A rectal wall involvement was histologically proved for 75 patients (56%). For the diagnosis of infiltration of the intestinal wall, TVUS and TRUS, respectively, had a sensitivity of 90.7% and 96.0%, a specificity of 96.5% and 100.0%, a positive predictive value of 97.1% and 100.0% and a negative predictive value of 88.9% and 95.2%. CONCLUSIONS: TVUS and TRUS have similar degrees of accuracy for predicting intestinal involvement. TVUS must be the first-line imaging process to perform for patients presenting with clinically suspected DIE. The question for the coming years is to define if it is necessary for TRUS to be carried out systematically in cases of clinically suspected DIE.

Hum Reprod. 2009 Apr;24(4):954-65. Epub 2008 Dec 18.

 

Endometrial fluid is a specific and non-invasive biological sample for protein biomarker identification in endometriosis.

Ametzazurra A, Matorras R, García-Velasco JA, Prieto B, Simón L, Martínez A, Nagore D.

Proteomika, S.L. Parque Tecnológico de Bizkaia, Edificio 801B, Derio, Vizcaya 48160, Spain.

BACKGROUND: The development of non-invasive diagnostic methods for endometriosis requires sensitive and disease specific biomarkers. Here, we describe the use of aspirated endometrial fluid from women with and without endometriosis as a novel biological sample for biomarker discovery. METHODS: Differential protein expression profiling of aspirates from women with early endometriosis (n = 14), advanced endometriosis (n = 32) and without evidence of the disease (n = 32) was assessed by two-dimensional gel electrophoresis (2-DE). A biomarker validation study was performed in an independent cohort (early endometriosis n = 6 and advanced endometriosis n = 14, controls n = 15). RESULTS: The analysis resulted in the identification of 31 proteins showing statistically significant differences in expression. The proteins identified are related to cell signalling, cell death and cell movement, processes that may be involved in the onset and/or progression of endometriosis. The differences in expression observed for 14-3-3 (signal transduction) and moesin (cytoskeletal structure) were confirmed in an independent group of endometriosis patients. CONCLUSIONS: Endometrial fluid represents a novel sample for proteomic analysis offering reliable, disease specific information on protein expression, facilitating the discovery of biomarkers for endometriosis. The results described here complement previous proteomic studies, providing new endometriosis-related proteins to be validated as diagnostic markers.

Publication Types:

J Clin Endocrinol Metab. 2009 Mar;94(3):876-83. Epub 2008 Dec 16.

 

Increased production of 17beta-estradiol in endometriosis lesions is the result of impaired metabolism.

Delvoux B, Groothuis P, D’Hooghe T, Kyama C, Dunselman G, Romano A.

GROW, School for Oncology and Developmental Biology, University Maastricht, and Department of Obstetrics and Gynecology, University Hospital Maastricht, 6202 AZ Maastricht, The Netherlands. b.delvoux@og.unimaas.nl

CONTEXT: substantial evidence suggests that the expression of steroid metabolizing enzymes in endometriosis is altered, turning the ectopic endometrium into a source of 17beta-estradiol. However, whether these differences result in a net increase in local 17beta-estradiol production/activity has not been shown. SUBJECTS AND METHODS: The activities of the most important steroidogenic enzymes synthesizing and inactivating 17beta-estradiol were determined by HPLC in matched eutopic and ectopic tissue from patients with endometriosis (n = 14) and in endometrium from controls (n = 20). RESULTS: Aromatase activity is negligible in the ectopic endometrium, whereas the activity of estrogen sulfatase is high though not different between ectopic, eutopic and control endometrium. The activity of 17beta-hydroxysteroid dehydrogenases (17beta-HSDs) converting estrone into 17beta-estradiol is higher in the ectopic compared to the eutopic endometrium in patients. The activity of 17beta-HSDs converting 17beta-estradiol back to estrone is significantly lower in the ectopic compared to the eutopic endometrium of both patients and controls. To evaluate the net metabolic capacity of tissues to synthesize 17beta-estradiol, we calculated the activity ratio between 17beta-HSDs synthesizing versus 17beta-HSDs inactivating 17beta-estradiol. This ratio is significantly higher in the ectopic compared to the eutopic endometrium of patients and controls, indicating a high synthesis of 17beta-estradiol in the ectopic locations. This is further supported by the elevated mRNA levels of the estrogen-responsive gene TFF1 in all ectopic compared to eutopic endometria. CONCLUSION: Endometriotic lesions have higher production of 17beta-estradiol than the eutopic endometrium of patients and controls. This is mostly the result of impaired metabolism.

Publication Types:

Hum Reprod. 2009 Mar;24(3):687-96. Epub 2008 Dec 16.

 

Sustained replication in endometrium of women with endometriosis occurs without evoking a DNA damage response.

Hapangama DK, Turner MA, Drury JA, Quenby S, Hart A, Maddick M, Martin-Ruiz C, von Zglinicki T.

School of Reproductive and Developmental Medicine, University of Liverpool, Liverpool Women’s Hospital, Crown Street, Liverpool L8 7SS, UK. dharani.hapangama@liverpool.ac.uk

BACKGROUND: To test our hypothesis that eutopic secretory phase endometrium from women with endometriosis is similar to proliferative phase endometrium from fertile women without endometriosis, we explored the expression of regulators of cell fate across the menstrual cycle. METHODS: Endometrial biopsies were taken from 73 women, comprising 38 women with surgically diagnosed active peritoneal endometriosis (Group 1) and 35 fertile women without endometriosis (Group 2). Nucleolin, proliferating cell nuclear antigen (PCNA), telomerase and histone gamma-H2AX expression was evaluated by immunohistochemistry and mean telomere length (TL) by quantitative PCR. RESULTS: We have immunolocalized nucleolin and gamma-H2AX in the benign premenopausal endometrium for the first time. All markers were present in the proliferative phase endometrium of all women. In Group 2, during the secretory phase, proliferative markers declined with a paradoxical increase in stromal gamma-H2AX. Women in Group 1, however, showed a persistent immunoreactivity for the proliferative markers, while the staining for gamma-H2AX decreased in secretory endometrium (P < 0.05). This difference between groups was significant in both stroma and glands for nucleolin (P < 0.0001), PCNA (P < 0.01) and gamma-H2AX (P < 0.05) in the secretory phase. We showed a positive correlation between mean TL and nucleolin expression (glandular r = 0.37, P = 0.002; stromal r = 0.4, P = 0.001), telomerase immunoreactivity (glandular r = 0.33, P = 0.009; stromal r = 0.4, P = 0.001) and glandular PCNA (r = 0.35, P = 0.004), whereas a negative correlation was seen between mean TL and gamma-H2AX (r = -0.28, P = 0.04). CONCLUSIONS: These findings demonstrate that the state of replication seen in secretory phase endometrium from women with active peritoneal endometriosis is not a simple extension of the proliferative phase.

Publication Types:

Hum Reprod. 2009 Mar;24(3):608-18. Epub 2008 Dec 16.

 

Anti-angiogenic effects of green tea catechin on an experimental endometriosis mouse model.

Xu H, Lui WT, Chu CY, Ng PS, Wang CC, Rogers MS.

Department of Obstetrics and Gynaecology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong.

BACKGROUND: The development of new blood vessels plays an essential role in growth and survival of endometriosis. Epigallocatechin gallate (EGCG) from green tea has powerful anti-angiogenic properties and our aim was to evaluate these properties in experimental endometriosis. METHODS AND RESULTS: Eutopic endometrium from endometriosis patients was transplanted s.c. to severely compromised immunodeficient mice, randomly treated i.p. with EGCG (anti-angiogenic and -oxidant), Vitamin E (a non-angiogenic antioxidant) or saline for 2 weeks. The endometrial implant, including adjacent host outer skin and subcutaneous layers plus inner abdominal muscle and peritoneum, was collected. New microvessels were determined by species-specific immunohistochemistry. Angiogenic factors in lesions and abdominal muscle were detected by quantitative real-time PCR. Apoptosis was studied by terminal deoxynucleotidyltransferase-mediated dUTP nick-end labelling and quantitative real-time PCR. In saline control, endometrial implants developed new blood vessels with proliferating glandular epithelium and were tightly adhered to host subcutaneous and abdominal muscle layers. After EGCG, endometriotic lesions were smaller than control (P < 0.05), and glandular epithelium was smaller and eccentrically distributed. Angiogenesis in lesions from the implant and adjacent tissues was under-developed, and microvessel size and density were lower (both P < 0.01) than control. mRNA for angiogenic vascular endothelial growth factor A, but not hypoxia inducible factor 1, alpha subunit, was significantly down-regulated in lesions after EGCG (P < 0.05). In addition, apoptosis in the lesions was more obvious, and nuclear factor kappa B and mitogen activated protein kinase 1 mRNA levels were up-regulated (P < 0.05) after EGCG treatment. No differences were observed with Vitamin E treatment. CONCLUSIONS: EGCG significantly inhibits the development of experimental endometriosis through anti-angiogenic effects.

Interact Cardiovasc Thorac Surg. 2009 Mar;8(3):349-52. Epub 2008 Dec 16.

 

Surgical treatment of catamenial pneumothorax: a single centre experience.

Ciriaco P, Negri G, Libretti L, Carretta A, Melloni G, Casiraghi M, Bandiera A, Zannini P.

Department of Thoracic Surgery, Scientific Institute and University Vita-Salute H San Raffaele, Milan, Italy. ciriaco.paola@hsr.it

We retrospectively reviewed our experience with catamenial pneumothorax (CP) in terms of treatment and follow-up. From 1993 to 2008, ten women presented at our department with CP. CP was right-sided in all patients: seven presented diaphragmatic defects including one endometriosis, five had apical bulla or blebs that in three patients were the only pathological findings. Surgical approach was thoracoscopic with a muscle-sparing thoracotomy when diaphragmatic defects where present. All patients underwent apical resection and apical pleurectomy associated in seven cases with diaphragmatic plication and chemical pleurodesis. After surgery nine patients underwent hormonal treatment: three were put on estrogen-progesterone complex treatment and six received gonadotropin-releasing hormone agonist (GnRH agonist). Recurrence rate was 40% and it was significantly correlated with estrogen-progesterone treatment (P<0.005). The mean follow-up was 52+/-32 months (range 14-168). At the present time, no recurrence has occurred in all women. Occurrence of CP is often underestimated. At the time of surgery the diaphragm should be carefully inspected for defects and/or endometriosis. Standard pleurodesis may not suffice and we suggest apical resection and apical pleurectomy associated with a diaphragmatic procedure when indicated. Hormonal treatment with GnRH agonist seems to improve the outcome.

BJOG. 2009 Jan;116(1):129; author reply 129-30.

 

Comment on:

Endometriosis and irritable bowel syndrome: co-morbidity or misdiagnosis?

Ferrero S, Camerini G, Ragni N, Remorgida V.

Publication Types:

Int J Gynaecol Obstet. 2009 Feb;104(2):161. Epub 2008 Dec 10.

 

Transvaginal ultrasound after bowel preparation to assist surgical planning for bowel endometriosis resection.

Pereira RM, Zanatta A, de Mello Bianchi PH, Chamié LP, Gonçalves MO, Serafini PC.

Huntington Reproductive Medicine Center, São Paulo, SP, Brazil.

Gynecol Obstet Invest. 2009;67(3):158-61. Epub 2008 Dec 11.

 

Histological confirmation of endometriosis in a 9-year-old girl suffering from unexplained cyclic pelvic pain since her eighth year of life.

Ebert AD, Fuhr N, David M, Schneppel L, Papadopoulos T.

German Endometriosis Research Center Berlin Level III, Department of Obstetrics and Gynecology, Vivantes Campus Humboldt, Berlin, Germany. andreas.ebert@vivantes.de

OBJECTIVE: Endometriosis is considered an estrogen-dependent disease of women in their reproductive age and characterized by the occurrence of stromal cells and endometrial-like glands outside the uterine cavity. PATIENT: A report of a 9-year-old premenarcheal girl who was transferred to the Endometriosis Research Center Berlin-Brandenburg Level III (Academic Teaching Hospital) because of cyclic pelvic pain since her 8th year of life. INTERVENTIONS: History, examination, abdominal ultrasound, laboratory tests, laparoscopic resection of visible lesions. Paraffin-embedded histology (HE staining) and immunohistochemistry. RESULTS: Endometriosis, defined as the presence of stromal tissue and epithelial glands, was confirmed both by HE staining and immunohistochemistry (CD10), respectively. CONCLUSIONS: Young pre- or perimenarcheal girls with chronic/cyclic pelvic pain can have endometriosis, and thus the possibility of endometriosis should be included in the differential diagnosis. Copyright 2008 S. Karger AG, Basel.

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BJOG. 2009 Jan;116(2):214-9.

 

Minimal access surgery in adolescent gynaecology.

Pandis GK, Michala L, Creighton SM, Cutner AS.

UCL Institute for Women’s Health, Elizabeth Garrett Anderson and Obstetric Hospital, London, UK.

The benefits of a minimally invasive approach are now well documented in adult women, and thus surgeons have embraced the notion of expanding such expertise in adolescence with measured enthusiasm and a great sense of responsibility. Faster recovery is likely to have a positive impact on schooling, while less adhesion formation may reduce future fertility issues. Gynaecologists performing minimally invasive procedures in adolescents ought to be aware of the steep learning curve required for achieving proficiency with complex laparoscopic surgery. In the group of rare congenital anomalies and advanced endometriosis, the best surgical results can only be achieved after careful preoperative planning by a multidisciplinary team.

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Mol Endocrinol. 2009 Feb;23(2):265-75. Epub 2008 Dec 12.

 

MicroRNA-regulated pathways associated with endometriosis.

Ohlsson Teague EM, Van der Hoek KH, Van der Hoek MB, Perry N, Wagaarachchi P, Robertson SA, Print CG, Hull LM.

Research Centre for Reproductive Health, University of Adelaide, South Australia 5005, Australia. maria.teague@adelaide.edu.au

Endometriosis is a prevalent gynecological disease characterized by growth of endometriotic tissue outside the uterine cavity. MicroRNAs (miRNAs) are naturally occurring posttranscriptional regulatory molecules that potentially play a role in endometriotic lesion development. We assessed miRNA expression by microarray analysis in paired ectopic and eutopic endometrial tissues and identified 14 up-regulated (miR-145, miR-143, miR-99a, miR-99b, miR-126, miR-100, miR-125b, miR-150, miR-125a, miR-223, miR-194, miR-365, miR-29c and miR-1) and eight down-regulated (miR-200a, miR-141, miR-200b, miR-142-3p, miR-424, miR-34c, miR-20a and miR-196b) miRNAs. The differential expression of six miRNAs was confirmed by quantitative RT-PCR. An in silico analysis identified 3851 mRNA transcripts as putative targets of the 22 miRNAs. Of these predicted targets, 673 were also differentially expressed in ectopic vs. eutopic endometrial tissue, as determined by microarray. Functional analysis suggested that the 673 miRNA targets constitute molecular pathways previously associated with endometriosis, including c-Jun, CREB-binding protein, protein kinase B (Akt), and cyclin D1 (CCND1) signaling. These pathways appeared to be regulated both transcriptionally as well as by miRNAs at posttranscriptional level. These data are a rich and novel resource for endometriosis and miRNA research and suggest that the 22 miRNAs and their cognate mRNA target sequences constitute pathways that promote endometriosis. Accordingly, miRNAs are potential therapeutic targets for treating this disease.

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Int J Gynaecol Obstet. 2009 Apr;105(1):39-42. Epub 2008 Dec 13.

 

Association of body mass index with severity of endometriosis in Korean women.

 

Yi KW, Shin JH, Park MS, Kim T, Kim SH, Hur JY.

Department of Obstetrics and Gynecology, College of Medicine, Korea University, Seoul, Korea.

OBJECTIVE: To investigate the relationship between endometriosis severity and body mass index (BMI). METHODS: Of 481 women seen for endometriosis at a university hospital in Korea, 153 had stage I, 113 had stage II, 110 had stage III, and 105 had stage IV disease. The patients’ BMIs were categorized according to World Health Organization criteria for Asian-Pacific populations. RESULTS: Women with early or mild endometriosis (stages I or II) had a significantly higher BMI than those with advanced disease (stages III or IV) (P<0.001). After adjusting for age, parity, and menstrual factors, an association between BMI and disease stage remained significant (P<0.001). CONCLUSION: Women with advanced-stage endometriosis had lower BMIs than those with minimal or mild disease, and BMI was significantly associated with disease severity.

Int J Cancer. 2009 Mar 15;124(6):1409-15.

 

Markers of inflammation and risk of ovarian cancer in Los Angeles County.

Wu AH, Pearce CL, Tseng CC, Templeman C, Pike MC.

Department of Preventive Medicine, University of Southern California, Keck School of Medicine, Los Angeles, CA 90089-9175, USA. annawu@usc.edu

Factors that increase inflammation have been suggested to influence the development of ovarian cancer, but these factors have not been well studied. To further investigate this question, we studied the role of talc use, history of endometrioisis and use of non-steroidal anti-inflammatory drugs (NSAIDs) and risk of ovarian cancer in a population-based case-control study in Los Angeles County involving 609 women with newly diagnosed epithelial ovarian cancer and 688 population-based control women. Risk of ovarian cancer increased significantly with increasing frequency and duration of talc use; compared to never users risk was highest among long-duration (20+ years), frequent (at least daily) talc users (adjusted relative risk (RR) = 2.08, 95% confidence interval (CI) = 1.34-3.23). A history of physician-diagnosed endometriosis was statistically significantly associated with risk (RR = 1.66, 95% CI = 1.01-2.75). Women who were talc users and had a history of endometriosis showed a 3-fold increased risk (RR = 3.12, 95% CI = 1.36-7.22). Contrary to the hypothesis that risk of ovarian cancer may be reduced by use of NSAIDs; risk increased with increasing frequency (per 7 times/week, RR = 1.27, 95% CI = 1.14-1.43) and years of NSAID use (per 5 years of use, RR = 1.25, 95% CI = 1.10-1.42); this was consistent across types of NSAIDs. We conclude that risk of ovarian cancer is significantly associated with talc use and with a history of endometriosis, as has been found in previous studies. The NSAID finding was unexpected and suggests that factors associated with inflammation are associated with ovarian cancer risk. This result needs confirmation with careful attention to the reasons for NSAID use.

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Fertil Steril. 2009 Mar;91(3):929.e9-11. Epub 2008 Dec 4.

 

A rare case of vulvar endometriosis in an adolescent girl.

Eyvazzadeh AD, Smith YR, Lieberman R, Quint EH.

Department of Obstetrics and Gynecology, School of Medicine, University of Michigan, Ann Arbor, Michigan 48105, USA.

OBJECTIVE: To describe a case of vulvar endometriosis in a teenager after a history of vulvar ulcers in the same location. DESIGN: Case report. SETTING: University medical center. PATIENT(S): A 13-year-old girl with a history of vulvar ulcers. MAIN OUTCOME MEASURE(S): None RESULT(S): A 13-yr-old female presented with painful, open vulvar ulcerations on the inner side of her labia minora. Biopsy revealed dermatitis with ulceration. One year later she noted an ulcer and blood in her undergarments. Biopsy results were consistent with endometriosis. Five years later, the lesions persisted and bled during menses. A bilateral labial excision was performed. Pathology again revealed endometriosis. CONCLUSION(S): Vulvar endometriosis is extremely unusual. This rare case of vulvar endometriosis in the same location as a previous vulvar ulcer is most likely due to ectopic transplantation of endometrial cells during a menstrual cycle. Excision is considered definitive treatment.

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Fertil Steril. 2009 Jan;91(1):301-2. Epub 2008 Dec 4.

 

Comment in:

Comment on:

Adhesions: if the patient could only be their own control: left eye versus right eye, etc.

ten Broek RP, van Goor H.

Publication Types:

Eur J Obstet Gynecol Reprod Biol. 2009 Feb;142(2):145-8. Epub 2008 Dec 6.

 

Endometriosis prophylaxis and treatment with the newly developed xenogenic immunomodulator RESAN in an animal model.

Szymanowski K, Chmaj-Wierzchowska K, Yantczenko A, Niepsuj-Biniaś J, Florek E, Opala T, Murawski M.

Department of Mother’s and Child’s Health, K. Marcinkowski University of Medical Sciences, Poznan, Poland. kp.szymanowski@wp.pl

OBJECTIVE: The objective was to assess the effectiveness of the newly developed immunomodulator RESAN in the prophylaxis and treatment of endometriosis induced in rats. STUDY DESIGN: The study was performed on 58 Wistar rats. Twelve weeks before endometriosis induction, the RESAN vaccine was administered to 24 rats (100 mg i.m. and 100 mg s.c.). Endometriosis induction was performed in 48 rats, which were divided into two groups: group I, the prophylaxis group, consisting of 24 previously vaccinated rats; and group II, the treatment group, comprising the other 24 rats, which had not been vaccinated. The graft (4 mm x 4 mm) of endometrium was attached to the parietal peritoneum. A sham operation was performed in 10 rats (group III). After 3 months, a second laparotomy was performed in all animals, and endometriotic foci were excised when present. RESAN was administered to the group II animals. After an additional 3 months, a third laparotomy was performed in all animals of the three groups. RESULTS: Positive, histologically confirmed endometriosis was found in 4.3% of the animals in group I and in 69.6% of group II rats (p<0.0001). Macroscopic assessment revealed endometriosis in 21.7% and 91.3% of animals in groups I and II, respectively (p<0.0001). At final laparotomy, 3 months after excision of the previously suspected foci, no signs of endometriosis were found according to both macroscopic assessment and histological examination. During the second laparotomy intraperitoneal adhesions were present in 13.0% of the animals in group I and in 61.0% of those in group II. No adhesions were present in group III. At the final laparotomy, the adhesions were present in only three of the animals in group II (p<0.0009). CONCLUSIONS: RESAN seems to be effective in both the prophylaxis and treatment of endometriosis, as well as in the prophylaxis of adhesions. Histological confirmation of endometriosis should be mandatory.

Hum Reprod. 2009 Mar;24(3):496-501. Epub 2008 Dec 4.

 

Management of endometriomas in women requiring IVF: to touch or not to touch.

Garcia-Velasco JA, Somigliana E.

IVI Madrid, Rey Juan Carlos University, Av. del Talgo 68, Madrid 28023, Spain. jgvelasco@ivi.es

The classic, unproven dogma that ovarian endometrioma should be removed in all infertile women prior to IVF has been recently questioned. There is currently insufficient data to clarify whether the endometrioma-related damage to ovarian responsiveness precedes or follows surgery. Both endometrioma-related injury and surgery-mediated damage may be claimed to be involved and the relative importance of these two insults remains to be clarified. Convincing evidence has emerged showing that responsiveness to gonadotrophins after ovarian cystectomy is reduced. Conversely, the impact of surgery on pregnancy rates is unclear since no deleterious effect has been reported. Of relevance here is that surgery exposes women to risk related to a demanding procedure whereas risks associated with expectant management are mostly anecdotal or of doubtful clinical relevance. We recommend proceeding directly to IVF to reduce time to pregnancy, to avoid potential surgical complications and to limit patient costs. Surgery should be envisaged only in presence of large cysts (balancing the threshold to operate with the cyst location within the ovary), or to treat concomitant pain symptoms which are refractory to medical treatments, or when malignancy cannot reliably be ruled out.

Arch Gynecol Obstet. 2009 Jul;280(1):131-5. Epub 2008 Dec 4.

 

Laparoscopic partial cystectomy for bladder endometriosis.

Walid MS, Heaton RL.

Medical Center of Central Georgia, Macon, GA, USA. mswalid@yahoo.com

Laparoscopic partial cystectomy performed for bladder endometriosis in selected patients requires advanced laparoscopic skills including pelvic dissection, suturing and intracorporeal knot tying. Cystoscopic skills to assess the extent of endometriosis involvement in the bladder and to place ureteral stents if endometriosis involves or is close to the trigone, ureters, or projected course of the intramural part of the ureter are also required. Previous authors have recommended the laparoscopic technique only with bladder endometriosis that is distant from the bladder neck, the ureteral orifices, and the trigone, to allow a resection margin of 1-2 cm. We find no reason to exclude patients with these involvements if the surgeon can safely do the resection and reconstruction. We report a 32-year-old patient referred by her urologist for the evaluation and treatment of biopsy-proven bladder endometriosis penetrating the bladder wall and mucosa above and to the right of the midline of the trigone approximately 1.5 in. in diameter with fibrotic scarring extending to the trigone and very close to the right ureteral orifice. The patient successfully underwent partial laparoscopic cystectomy as described in the body of the paper.

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Hum Reprod. 2009 Feb;24(2):325-32. Epub 2008 Dec 1.

 

Macrophage expression in endometrium of women with and without endometriosis.

Berbic M, Schulke L, Markham R, Tokushige N, Russell P, Fraser IS.

Department of Obstetrics and Gynaecology, Queen Elizabeth II Research Institute for Mothers and Infants, Sydney 2006, Australia. m.berbic@usyd.edu.au

BACKGROUND: Endometriosis is an inflammatory condition, characterized by the presence of endometrial-like tissue outside the uterus. The immune system provides a defence mechanism in response to foreign pathogens, and macrophages play important roles in this response. Activation of macrophages has been reported in peritoneal fluid and ectopic endometriotic lesions; however, controversy exists regarding the composition and function of macrophage populations in eutopic endometrium of women with and without endometriosis. This study aimed to quantify macrophages in eutopic endometrium of women with and without endometriosis, during the early, mid and late proliferative and menstrual phases of the cycle. METHODS: Paraffin-embedded endometrial curettage blocks were selected from pathology archives. Seventy-six specimens from women with and without endometriosis were analysed using standard immunohistochemical techniques with CD68-PGM1 (phosphoglucomutase 1) clone antibody. Macrophages were counted according to their morphology over several fields of view. RESULTS: A significant increase in macrophage cell numbers was shown in eutopic endometrium in women with endometriosis (mean +/- SD, 182.7 +/- 72.9/mm(2)) during all stages of the proliferative phase compared with normal controls (101.6 +/- 53.4/mm(2); P < 0.001). Significant increase in macrophage density occurred in the control group during the mid-menstrual phase, Days 3-4 (P < 0.01), which was not observed in women with endometriosis. CONCLUSIONS: This study further supports an association between immune changes in eutopic endometrium and presence of endometriosis. However, it remains uncertain if eutopic immune changes are primary or secondary occurrences.

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Int J Gynecol Pathol. 2009 Jan;28(1):23-8.

 

Extrauterine adenomyoma with atypical (symplastic) smooth muscle cells: a report of 2 cases.

Stewart CJ, Leung YC, Mathew R, McCartney AL.

Department of Histopathology, King Edward Memorial Hospital, Perth, Western Australia, Australia. colin.stewart@health.wa.gov.au

Adenomyomas are circumscribed tumorlike masses most often involving the uterus and consisting of endometrioid glands, stroma, and smooth muscle tissue. They are uncommon in extrauterine sites and in this situation it may be unclear whether such lesions represent foci of endometriosis with marked smooth muscle hyperplasia/metaplasia, uteruslike mass lesions, or leiomyomas with entrapped endometriotic glandular and stromal elements. In this report 2 cases of extrauterine adenomyoma are presented in which the smooth muscle component showed focal atypical (symplastic) cytologic appearances.

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Contraception. 2009 Jan;79(1):29-34. Epub 2008 Sep 25.

Implanon versus medroxyprogesterone acetate: effects on pain scores in patients with symptomatic endometriosis–a pilot study.

Walch K, Unfried G, Huber J, Kurz C, van Trotsenburg M, Pernicka E, Wenzl R.

Division of Gynecological Endocrinology and Reproductive Medicine, Department of Obstetrics and Gynecology, Medical University of Vienna, Vienna, Austria.

BACKGROUND: Implanon has been reported to be effective in the treatment of dysmenorrhea. We compared the therapeutic efficacies of depot medroxyprogesterone acetate (DMPA) and Implanon with regard to pain relief in women with endometriosis. STUDY DESIGN: In a clinical research center at a university hospital, 41 patients with dysmenorrhea, nonmenstrual pelvic pain and dyspareunia associated with histologically proven endometriosis were included in an open, prospective, randomized, controlled clinical trial. Twenty-one women were assigned by computer-generated randomization to receive Implanon, and 20 women to receive DMPA. As main outcome measures of this pilot study, we evaluated pain improvement quantified according to visual analog scale score, side effects, vaginal bleeding patterns, withdrawal rate and overall degree of satisfaction. RESULTS: During a follow-up period of 1 year, we ascertained a clear improvement in pain intensity for both treatment options. After 6 months, the average decrease in pain was 68% in the Implanon group and 53% in the DMPA group. The side-effects profile and the overall degree of satisfaction after study termination were comparable for both treatment options. CONCLUSION: Concerning pain relief, the therapeutic efficacy of the contraceptive implant Implanon is not inferior to that of DMPA in symptomatic endometriosis.

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