Best Pract Res Clin Obstet Gynaecol. 2006 Feb 21; [Epub ahead of print] Experimental adenomyosis.
Greaves P, White IN.
MRC Molecular Endocrinology Group, Cancer Studies and Molecular Medicine, Robert Kilpatrick Building, University of Leicester, Leicester LE2 7LX, UK.
Adenomyosis has been reported in a number of different animal species, whereas endometriosis appears limited to humans and non-human primates. This suggests a different aetiology of the two conditions. Adenomyosis develops spontaneously in certain strains of laboratory mice. Its incidence in mice can be markedly enhanced by systemic exposure to various hormonal agents, including prolactin, progesterone, synthetic progestins, certain oestrogenic agents, as well as tamoxifen and toremifene. The precise hormonal changes necessary remain unclear, although the evidence suggests that adenomyosis in this model is not due to a simple oestrogenic effect. Study of the pathological and molecular alterations in this model indicates that disturbances to the uterine stroma, blood vessels and myometrium are also important factors in the development of adenomyosis.
PMID: 16500151 [PubMed – as supplied by publisher]
Life Sci. 2006 Feb 22; [Epub ahead of print] Impaired NK-cell-mediated cytotoxic activity and cytokine production in patients with endometriosis: A possible role for PCBs and DDE.
Quaranta MG, Porpora MG, Mattioli B, Giordani L, Libri I, Ingelido AM, Cerenzia P, Di Felice A, Abballe A, De Felip E, Viora M.
Department of Drug Research and Evaluation, Istituto Superiore di Sanita, Viale Regina Elena, 299 00161, Rome, Italy.
Endometriosis is a gynaecological disorder characterized by the presence and growth of endometrial tissue in ectopic sites. In this study we examined the immunological functions of patients with endometriosis and serum level of PCBs and p,p’-DDE to verify the impact of these environmental contaminants on the dysregulation of immune functions. We found that proliferative responses and immunoglobulin production were not dysregulated in patients with endometriosis while NK cell activity was significantly down-regulated in these patients. Moreover, a significant down-regulation of IL-1beta and IL-12 production was found in patients with respect to controls. Serum levels of PCBs and p,p’-DDE were found to be significantly higher in women with endometriosis than in the control group, with respect to the sum of the congeners most prominent in human tissues. In particular, total PCBs concentration in patients with endometriosis and controls was respectively 330 and 160 ng/g fat with respect to the most abundant congeners, while p,p’-DDE concentration was of 770 and 310 ng/g fat. Moreover, we found that normal human PBMC pulsed with PCBs, p,p’-DDE and their combination showed a significant down-regulation of NK cell cytotoxic activity and IL-1beta and IL-12 production. These findings suggest that changes in specific immune parameters correlate with elevated serum PCBs and DDE levels and endometriosis.
PMID: 16499933 [PubMed – as supplied by publisher]
AJR Am J Roentgenol. 2006 Mar;186(3):616-20.
Abdominal wall endometriosis: clinical presentation and imaging features with emphasis on sonography.
Hensen JH, Van Breda Vriesman AC, Puylaert JB.
Department of Radiology, MCH Westeinde Hospital, The Hague, Lijnbaan 32, PO Box 432, NL-2501 CK, The Netherlands.
OBJECTIVE: The purpose of our study was to evaluate clinical findings and sonographic features of abdominal wall endometriosis and also to report its CT and MR appearance. MATERIALS AND METHODS: A computerized search of our institution’s database over a 5-year period was performed, yielding 12 surgically proven cases of abdominal wall endometriosis that were retrospectively studied. All patients had undergone sonography including power Doppler examination. Additional CT was performed in one patient and MRI in four. Pathologic material was preoperatively obtained by sonographically guided puncture in six patients. The clinical data were analyzed, and the imaging studies were reviewed by two radiologists working in consensus. RESULTS: All patients had a history of at least one prior cesarean section. All presented with focal pain near the surgical scar, which was cyclic in three patients. Nine patients presented with a palpable mass near the scar. Sonography detected 11 lesions within the abdominal wall, with a mean diameter of 25 mm. All lesions were hypoechoic, vascular, and solid, with some cystic changes in one. The calculated frequency of abdominal wall endometriosis is approximately 0.8% of all women who had a cesarean delivery. CONCLUSION: Abdominal wall endometriosis frequently presents with noncyclic symptoms. Imaging findings of a solid mass near a cesarean section scar strongly suggest its diagnosis.
PMID: 16498086 [PubMed – in process]
Hum Reprod. 2006 Feb 22; [Epub ahead of print] Laparoscopic excision of posterior vaginal fornix in the treatment of patients with deep endometriosis without rectum involvement: surgical treatment and long-term follow-up.
Angioni S, Peiretti M, Zirone M, Palomba M, Mais V, Gomel V, Melis GB.
Division of Gynecology, Obstetrics and Pathophysiology of Human Reproduction, Department of Surgery, Maternal-Fetal Medicine, and Imaging, University of Cagliari, Cagliari, Italy.
BACKGROUND: The objective of the study is to evaluate the short- and long-term efficacy of complete laparoscopic excision of deep endometriosis, without rectum involvement, with the opening and partial excision of the posterior vaginal fornix. METHODS: Thirty-one patients were included in the study with symptomatic extensive disease including involvement of the cul-de-sac, rectovaginal space and posterior vaginal fornix without rectum involvement. Endoscopic surgery was performed with complete separation of rectovaginal space and in-block resection of the diseased tissue, opening and partial excision of the posterior vaginal fornix and vaginal closure either by laparoscopic or by vaginal route. Patients filled in questionnaires on pain before and 12, 24, 36, 48 and 60 months after surgical treatment. RESULTS: No intraoperative complications were observed; 65% were free of analgesic on post-operative day 2, 38% had total remission of chronic pain and 22% were improved; 38% had total remission of dysmenorrhoea and 22% were improved; 45% had total remission of dyspareunia and 25% were improved. Follow-up improvement of symptoms was statistically significant and was maintained for 5 years without recurrence of the disease or repeated surgery (P < 0.001). CONCLUSION: Complete surgical resection of deep infiltrative endometriosis with excision of the adjacent tissue of the posterior vaginal fornix improves quality of life with persistence of results for long time in patients not responsive to medical treatment.
PMID: 16495305 [PubMed – as supplied by publisher]
BJOG. 2006 Mar;113(3):251-6.
The use of ultrasound-based ‘soft markers’ for the prediction of pelvic pathology in women with chronic pelvic pain–can we reduce the need for laparoscopy?
Okaro E, Condous G, Khalid A, Timmerman D, Ameye L, Huffel SV, Bourne T.
Early Pregnancy, Gynaecological Ultrasound and Minimal Access Surgery Unit, St George’s Hospital Medical School, London, UK. emeka.okaro@bartsandthelondon.nhs.uk
OBJECTIVE: To assess the accuracy of new transvaginal ultrasound-scan-based markers and to compare them to conventional ultrasound methods used in the detection of common pelvic pathology in women with chronic pelvic pain (CPP). DESIGN: A prospective observational study. SETTING: Teaching hospital. POPULATION: A total of 120 consecutive women with CPP undergoing transvaginal ultrasonography before either diagnostic or operative laparoscopy. METHODS: Anatomical abnormalities, e.g. endometrioma or hydrosalpinx (hard markers), were documented. The woman was then assessed for the presence or absence of ‘soft markers’ (reduced ovarian mobility and site-specific pelvic tenderness). MAIN OUTCOME MEASURE: Presence or absence of pelvic pathology noted during laparoscopy. RESULTS: Seventy women had pelvic pathology, of whom 51 had endometriosis alone, 7 both endometriosis and pelvic adhesions, 6 pelvic adhesions, 1 hydrosalpinx with endometriosis and 5 hydrosalpinx and pelvic adhesions. The likelihood ratio for the hard markers was infinity (specificity was 100%), for the soft makers 1.9 (95% CI 1.2-3.1) and for a ‘normal’ ultrasound 0.18 (0.09-0.34). The pre-test probability of pelvic disease in our population of women with CPP was 58%, and this probability of disease was raised to 100% with the presence of hard markers and to 73% with the presence of soft markers. The pre-test probability of 58% fell to 20% when ultrasound finding was found to be normal. CONCLUSION: This new approach improves the detection and exclusion of significant pathology in women with CPP and may lead to a reduction in the number of unnecessary laparoscopies carried out on women with CPP.
PMID: 16487194 [PubMed – in process]
Biol Reprod. 2006 Feb 15; [Epub ahead of print] Induced Endometriosis in the Baboon (Papio anubis) Increases the Expression of the Proangiogenic Factor CYR61 (CCN1) in Eutopic and Ectopic Endometria.
Gashaw I, Hastings JM, Jackson KS, Winterhager E, Fazleabas AT.
The expression of human CYR61 mRNA (cysteine-rich, angiogenic inducer, 61, CCN1) has been previously shown to be deregulated in the endometrium of women with endometriosis. We have chosen the baboon model (Papio anubis) of induced endometriosis to clarify if CYR61 mRNA upregulation is predisposed to an inappropriately differentiated endometrium or is deregulated as a response to the presence of ectopic lesions. In the baboon, endometrial CYR61 mRNA expression underwent moderate cyclical variation with a significant 7.3-fold increase detected at day 2 post menses when compared to endometrium from the proliferative and secretory phases. The CYR61 transcript was extensively upregulated in the eutopic endometrium from all baboons with induced endometriosis, as early as one month post inoculation of menstrual tissue into the peritoneal cavity. CYR61 mRNA expression then decreased throughout progression of the disease, but remained higher compared to control tissues. Ectopic endometriotic lesions showed a further increase of CYR61 mRNA, with highest expression found in red lesions. Moreover, the expression levels of CYR61 transcripts correlated significantly to that of VEGF. Immunohistochemistry revealed the presence of CYR61 protein in glandular and luminal epithelial cells as well as in blood vessels of eutopic and ectopic endometrium. Similar to humans, increased levels of CYR61 mRNA correlated with the development of endometriosis in baboons. The increase of CYR61 mRNA in eutopic endometrium of baboons following peritoneal inoculation with menstrual endometrium provides evidence for a feedback mechanism from resulting lesions to induce a shift in gene expression patterns in the eutopic endometrium.
PMID: 16481591 [PubMed – as supplied by publisher]
Life Sci. 2006 Feb 13; [Epub ahead of print] Prunella stica inhibits the proliferation but not the prostaglandin production of Ishikawa cells.
Huang JC, Ruan CH, Tang K, Ruan KH.
Department of Obstetrics and Gynecology, University of Texas Health Science Center, 6431 Fannin Street, Houston, TX 77030, USA.
Chinese herbs have been used to relieve dysmenorrhea associated with endometriosis. Active components in the herbs and their mechanisms of action remain unknown. Prunella stica, a Chinese herb commonly used to treat dysmenorrhea, was chosen for the present studies. Its effects were investigated on Ishikawa cells, an epithelial cell line derived from human endometrium. Cell proliferation and inhibition of interleukin 1beta (IL-1beta) induced prostaglandin (PG) production were examined. To learn more about the active components, 120 fractions were collected from the crude extract and each fraction was tested individually. To further characterize the active components, aliquots of fractions with activity were subject to mass spectrometry analysis. Crude extract of P. stica inhibited the proliferation of Ishikawa cells but not the IL-1beta induced PG production. Active components of P. stica clustered around fractions 64 and 92; they increased cell doubling time from 18.6 to 26.2 and 29.4h, respectively. Mass spectrometry analysis showed fractions 64 and 92 consisted of three components whose molecular weights were 337, 348 and 430 Daltons. The therapeutic effects of P. stica reside, in part, in inhibiting the proliferation of the epithelial cells derived from human endometrium. The active components are small molecules.
PMID: 16481008 [PubMed – as supplied by publisher]
Reprod Biomed Online. 2006 Feb;12(2):174-81.
Menstrual effluent in endometriosis shows no difference in volume, VEGF-A, MMP2 and MMP9 or sFLT.
Malik S, Day K, Perrault I, Charnock-Jones DS, Smith SK.
Reproductive Medicine Unit, The Elizabeth Garrett Anderson and Obstetric Hospital, Huntley Street, London, WCIE 6DH, UK. shazymalik@yahoo.co.uk
Since retrograde menstruation is considered a key event in the aetiology of endometriosis, this study sought to determine whether the menstrual effluent of women with this condition is different from that of those with a normal pelvis. As the amount of blood lost during menstruation is thought to be higher in this group, measured objective menstrual blood loss (MBL) was measured. In addition, factors enhancing both ectopic implantation of endometrium and its subsequent growth (by establishing a neo-vasculature) were chosen for study. Our hypothesis was that they are increased in the menstrual effluent of women with endometriosis. The study showed that at the time of menstruation, there is no difference in MBL or in the volume of menstrual effluent between women with endometriosis and those with a normal pelvis at laparoscopy. In addition, vascular endothelial growth factor-A (VEGF-A) message and protein, soluble truncated receptor sVEGF-R1 (sFLT), matrix metalloproteinase (MMP) 2 and MMP9 activities were also shown to be similar between the two groups. It is concluded that the enhanced expression of VEGF-A and MMP in the peritoneal fluid and ectopic lesions of endometriotic patients may be a secondary event, resulting from an innate difference in peritoneal and systemic factors rather than in the endometrium, causing an abnormal peritoneal response to menstrual debris and facilitating its ectopic implantation.
PMID: 16478582 [PubMed – in process]
Actas Dermosifiliogr. 2005 Jan-Feb;96(1):43-5.
[Umbilical cutaneous endometriosis associated with a large uterine myoma] [Article in Spanish] Perez-Cejudo JA, Pique E, Arduan I, Palacios S, Sanchez C, Rodriguez M, Morales R.
Seccion de Dermatologia, Hospital General de Lanzarote, 35500 Arrecife-Lanzarote, Las Palmas, Spain. japcejudo@terra.es
We present a 44-year-old female patient who was being studied by the Gynecology Department because of the presence of large abdominal masses which proved to be leiomyomas on histological analysis. The Dermatology Department was consulted because of an asymptomatic umbilical tumor which had been developing for 5 years. Upon histological examination, we observed glands with angular lumens that showed decapitation secretion distributed throughout the dermis, surrounded by a cellular stroma with extravasated erythrocytes.
PMID: 16476332 [PubMed – in process]
Gynecol Oncol. 2006 Feb 10; [Epub ahead of print] Association between endometriosis and cancer: A comprehensive review and a critical analysis of clinical and epidemiological evidence.
Somigliana E, Vigano’ P, Parazzini F, Stoppelli S, Giambattista E, Vercellini P.
Department of Obstetrics, Gynecology and Neonatology, Ospedale Maggiore Policlinico, Mangiagalli and Regina Elena, Via Commenda 12, 20122 Milan, Italy; CROG Center for Research in Obstetrics and Gynaecology, Viale Caldara 39, 20122 Milan, Italy.
OBJECTIVE.: This review was aimed to critically evaluate observational, cohort, and case-control studies performed so far in order to assess the association between endometriosis and malignant diseases. Based on the observations herein presented, clinical indications that might avoid physicians’ mismanaging of affected patients are proposed. METHODS.: Search strategies included online searching of the MEDLINE database and hand searching of relevant publications and reviews. Additional reports were collected by systematically reviewing all references from retrieved papers. RESULTS.: Endometriosis is not associated with an increased risk of cancer in general. Data from large cohort and case-control studies indicate an increased risk of ovarian cancers in women with endometriosis. The observed effect sizes are modest varying between 1.3 and 1.9. Evidence from clinical series consistently demonstrates that the association is confined to the endometrioid/clear-cell histotypes. Available studies are characterized by several limitations, some of which potentially bias results towards the null hypothesis whereas others leading to overestimate the association. Evidence for an association with melanoma and non-Hodgkin’s lymphoma is increasing but still to be verified whereas an increased risk for other gynecological cancer types is not supported. CONCLUSIONS.: Epidemiological findings on the association between endometriosis and cancer are still elusive. At present, endometriosis should not be considered a medical condition associated with a clinically relevant risk of any specific cancer. On the basis of the present findings, modifications of the standard treatment options for the disease are not justifiable.
PMID: 16473398 [PubMed – as supplied by publisher]
Endocrinology. 2006 Feb 9; [Epub ahead of print] Continuous Human Metastin 45-54 Infusion Desensitizes GPR54-Induced GnRH Release Monitored Indirectly in the Juvenile Male Rhesus Monkey (Macaca mulatta): A Finding With Therapeutic Implications.
Seminara SB, Dipietro MJ, Ramaswamy S, Crowley WF Jr, Plant TM.
Reproductive Endocrinology Unit (S.B.S., W.F.C.,Jr.), Massachusetts General Hospital, Boston, MA, Department of Cell Biology and Physiology (M.J.DiP., S.R., T.M.P.), University of Pittsburgh, Pittsburgh, PA.
The effect of continuous administration of the C-terminal fragment of metastin, the ligand for the G protein-coupled receptor, GPR54, on GnRH-induced LH secretion was examined in 3 agonadal, juvenile male monkeys whose responsiveness to GnRH was heightened by pretreatment with a chronic pulsatile iv infusion of synthetic GnRH. After bolus injection of 10 microg human (hu) metastin 45-54 (equivalent to kisspeptin 112-121), the GPR54 agonist was infused continuously at a dose of 100 microg/h and elicited a brisk LH response for approximately 3 h. This rise was then followed by a precipitous drop in LH despite continuous exposure of GPR54 to metastin 45-54. On day 4, during the final 3 h of the infusion, single boluses of hu metastin 45-54 (10 microg), NMDA (10 microg/kg) and GnRH (0.3 microg) were administered to interrogate each element of the metastin-GPR54-GnRH-GnRH receptor cascade. Although the NMDA and GnRH boluses were able to elicit LH pulses, that of hu metastin 45-54 was not, demonstrating functional integrity of GnRH neurons (NMDA) and GnRH receptors (NMDA and GnRH), but desensitization of GPR54. The desensitization of GPR54 by continuous hu metastin 45-54 administration has therapeutic implications for a variety of conditions currently being treated by GnRH and its analogs, including restoration of fertility in patients with abnormal GnRH secretion (i.e. idiopathic hypogonadotropic hypogonadism, hypothalamic amenorrhea), and selective, reversible suppression of the pituitary-gonadal axis to achieve suppression of gonadal steroids (i.e. precocious puberty, endometriosis, uterine fibroids, and prostate cancer).
PMID: 16469799 [PubMed – as supplied by publisher]
Sichuan Da Xue Xue Bao Yi Xue Ban. 2006 Jan;37(1):118-22.
[Expression of matrix metalloproteinase and tissue inhibitor of metalloproteinase in adenomyosis] [Article in Chinese] Qiu F, Gao XM, Luo GL, Yang KX, Wang H, Liu H, Wen Y.
Gynecology, West China Second Hospital, Sichuan University, Chengdu 610041, China.
OBJECTIVE: To investigate the expressions of matrix metalloproteinase -2, -3 (MMP-2,-3) and tissue inhibitor of metalloproteinase-2 (TIMP-2) in internal uterine endometriosis tissue and endometrium from women with and without endometriosis throughout the menstrual cycle. METHODS: Immunohistochemical staining of tissues was performed to study the expressions and locations of MMP-2, MMP-3, TIMP-2 between women with and without endometriosis. The real-time PCR technique was applied to detected the mRNA expressions of MMP-2, MMP-3 and TIMP-2. RESULTS: We found that ectopic endometrium from patients with endometriosis expressed higher levels of MMP-2 and MMP-3 and lower levers of TIMP-2 than normal controls did (P < 0.05). MMP-2 and MMP-3 were detected strongly in both stromal and epithelial cells of ectopic endometrium from patients with endometriosis, when mostly detected in the epithelial cells in the control group. All eutopic and ectopic endometrium samples from women with and without endometriosis throughout the menstrual cycle showed similar expressions of MMP-2, MMP-3 and TIMP-2. Quantitative expressions of MMP-2 mRNA, MMP-3 mRNA and TIMP-2 mRNA were significantly lower in eutopic endometrium from controls compared with ectopic endometrium from patients with endometriosis (P < 0.05). Eutopic endometrium from controls in the proliferative phase showed significantly increased expressions of MMP-2 mRNA compared with that in the secretory phase (P < 0.05). CONCLUSION: The results suggest that ectopic endometrium with adenomyosis has more invasiveness and is prone to peritoneal implantation maybe to involved in the high expressions of MMP-2 and MMP-3 and the less expressions of TIMP-2 than endometrium from women without adenomyosis does.
PMID: 16468658 [PubMed – in process]

Adv Anat Pathol. 2006 Jan;13(1):8-15.
p16 expression in the female genital tract and its value in diagnosis.
O’Neill CJ, McCluggage WG.
Department of Pathology, Royal Group of Hospitals Trust, Grosvenor Road, Belfast BT12 6BL, Northern Ireland.
p16 is a cyclin-dependent kinase-4 inhibitor that is expressed in a limited range of normal tissues and tumors. In recent years, immunohistochemistry with p16 antibodies has been used as a diagnostic aid in various scenarios in gynecologic pathology. Diffuse (as opposed to focal) positivity with p16 in the cervix can be regarded as a surrogate marker of the presence of high-risk human papillomavirus (HPV). In cervical squamous lesions, p16 is positive in most high-grade cervical intraepithelial neoplasia (CIN) and in some cases of low-grade CIN, usually those associated with high-risk HPV. p16 may be useful to identify small focal high-grade CIN lesions, to distinguish some cases of CIN involving immature metaplastic squamous epithelium from immature metaplastic squamous epithelium not involved by CIN and to distinguish high-grade CIN from benign mimics. Most cervical carcinomas of squamous, glandular, and small cell type are p16-positive. In cervical glandular lesions, p16 is useful, as part of a panel, in the distinction between adenocarcinoma in situ (diffusely positive) and benign mimics, including tuboendometrial metaplasia and endometriosis, which are usually p16-negative or focally positive. p16 may be used, in combination with other markers, to distinguish between a cervical adenocarcinoma (diffuse positivity) and an endometrioid-type endometrial adenocarcinoma (negative or focally positive). Some uterine serous carcinomas are diffusely positive. In the vulva, p16 is positive in HPV-associated vulval intraepithelial neoplasia (VIN) but negative in VIN not associated with HPV. Similarly, HPV-associated invasive squamous carcinomas are p16-positive, whereas the more common non-HPV-associated neoplasms are largely negative or focally positive. In the uterus, p16 positivity is more common and widespread in leiomyosarcomas than leiomyomas, and this may be a useful aid to diagnosis, although problematic uterine smooth muscle neoplasms have not been extensively studied. Metastatic cervical adenocarcinomas in the ovary are usually diffusely p16-positive, and because these may closely mimic a primary ovarian endometrioid or mucinous adenocarcinoma, this may be a valuable diagnostic aid, although p16 expression in primary ovarian adenocarcinomas of these morphologic subtypes has not been widely investigated. Some ovarian serous carcinomas, similar to their uterine counterparts, are p16-positive.
Publication Types: ? Review
PMID: 16462152 [PubMed – indexed for MEDLINE]

Arch Gynecol Obstet. 2006 Mar 9; [Epub ahead of print] Endometriosis associated with Stage IA clear cell ovarian carcinoma in a woman with IVF-ET treatments in the Yale Series.
Matalliotakis I, Mahutte NG, Koukoura O, Arici A.
Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Yale University School of Medicine, New Have, CT, USA.
A 42-year-old woman with Stage IA, grade 3 clear cell ovarian carcinoma arising within an endometrioma after multiple ovarian stimulation attempts was a unique case from a total of 900 patients who underwent laparoscopy for infertility and pelvic pain between 1996 and 2002 at Yale University. Her previous treatments included two laparoscopic cystectomies for left ovarian endometriomas and four cycles of IVF-ET that resulted in one miscarriage and two successful pregnancies. Although it has been suggested that controlled ovarian hyperstimulation may predispose to the development of ovarian cancer, more recent studies postulate a protective effect if fertility treatments ultimately result in successful pregnancy. Our unusual case serves as a reminder that clear cell adenocarcinoma may coexist with endometriosis, and that parity does not necessarily protect infertility patients against the development of ovarian cancer.
PMID: 16525789 [PubMed – as supplied by publisher]
J Clin Endocrinol Metab. 2006 Mar 7; [Epub ahead of print] Extracellular Matrix Metalloproteinase Inducer (EMMPRIN) Regulates Metalloproteinases in Human Uterine Endometrium.
Braundmeier AG, Fazleabas AT, Lessey BA, Guo H, Toole BP, Nowak RA.
Dept. of Animal Sciences, University of Illinois, Urbana, Illinois; Dept. of Obstetrics and Gynecology, University of Illinois, Chicago, Illinois; Dept. of Anatomy and Cell Biology, Tufts University, Boston, Massachusetts; Dept of Cell Biology and Anatomy, Medical University of South Carolina, Charleston, SC 29425, Dept of Reproductive Endocrinology, Greenville Hospital System, Greenville, SC 29605.
Context: Endometrial remodeling occurs during each menstrual cycle in women and also during the establishment of endometriosis. Both processes involve the production of metalloproteinases (MMPs) by uterine endometrial cells. Objective: To determine if tissue remodeling and endometrial invasion involve activation of MMPs by extracellular matrix metalloproteinase inducer (EMMPRIN). Main Outcome Measures: EMMPRIN expression was examined by immunohistochemistry and real time PCR in ectopic and eutopic endometrium. For functional assays, human uterine fibroblasts (HUF) were treated in the absence or presence of either IL-1beta (10 ng/ml) or purified native EMMPRIN (0.5 or 1 microg/ml) for 24 h. Cellular RNA and conditioned medium were assayed by real-time PCR or immunoblotting. Results: EMMPRIN protein localized to epithelial and fibroblast cells of eutopic and ectopic endometrium. The pattern of localization was regulated by ovarian hormones. EMMPRIN mRNA levels varied throughout the menstrual cycle in parallel with the cyclic changes in estradiol. EMMPRIN treatment (0.5 microg/ml) of HUF cells stimulated MMP-1 (5.23 fold) and MMP-2 (8.55) but not MMP-3 mRNA levels over control cells (P < 0.05). EMMPRIN treatment (1 microg/ml) stimulated endogenous EMMPRIN (1.6 fold) mRNA levels (P > 0.05). IL-1beta stimulated MMP-1 (5.6 fold), MMP-2 (2.8 fold) and MMP-3 (75 fold) gene expression but not EMMPRIN over control cells (P < 0.05). Both EMMPRIN and IL-1beta treatments stimulated MMP-1, 2 and 3 but not EMMPRIN protein secretion, with 0.5 microg/ml producing the greatest response. Conclusions: The ability of EMMPRIN to stimulate MMP secretion by endometrial fibroblasts indicates its potential role in uterine remodeling and the pathogenesis of endometriosis.
PMID: 16522689 [PubMed – as supplied by publisher]
Gynecol Endocrinol. 2006 Jan;22(1):9-17.
High-dose pilot study with the novel progestogen dienogestin patients with endometriosis.
Schindler AE, Christensen B, Henkel A, Oettel M, Moore C.
Department of Gynecology and Obstetrics, University of Essen, Essen, Germany.
High-dose dienogest (20 mg/day) was used for the treatment of endometriosis in women aged 18-52 years after laparoscopic and histological diagnosis of endometriosis and staging according to the revised American Fertility Society criteria. Treatment efficacy was analyzed objectively by second-look laparoscopy, and serum hormone measurements and evaluation of endometriosis-related symptoms were performed done and side-effects recorded. Compared with other high-dose progestin therapies, treatment with dienogest was shown to be effective even in stage IV endometriosis. The side-effect profile of the high-dose dienogest treatment appears to be highly favorable compared with other treatments. Neither the menopausal symptoms caused by therapy with gonadotropin-releasing hormone agonists nor the adverse androgen-related effects induced by danazol were observed. Therefore, long-term high-dose dienogest therapy can be recommended particularly for women with progressive endometriosis.
PMID: 16522528 [PubMed – in process]
Best Pract Res Clin Endocrinol Metab. 2006 Mar;20(1):63-75.
Endocrine disrupters and female reproductive health.
McLachlan JA, Simpson E, Martin M.
Department of Pharmacology, Tulane University School of Medicine, and Environmental Endocrinology Laboratory, Center for Bioenvironmental Research, Tulane and Xavier Universities, New Orleans, LA 70118, USA.
There is growing evidence of the impact of estrogenic contaminants in the environment. Studies have shown that male fish in detergent-contaminated water express female characteristics, turtles are sex-reversed by polychlorinated biphenyls (PCBs), male frogs exposed to a common herbicide form multiple ovaries, pseudohermaphroditic offspring are produced by polar bears, and seals in contaminated water have an excess of uterine fibroids. Endocrine-disrupting chemicals (those found in the external environment that can mimic or inhibit endogenous hormones) mostly exhibit estrogenic effects, but a few are anti-estrogenic or anti-androgenic. Many of these compounds are industrial contaminants, such as pesticides and plasticizers, and others are natural phytoestrogens found in plants such as soy and in herbal supplements. Recent work shows that human development can also be feminized by exposure to estrogenic chemicals. Estrogen is the key hormone in the initiation (puberty) and the end (menopause) of reproductive life in women and thus of considerable importance in women’s health. The same chemicals that affect wildlife may affect breast growth and lactation, and could have a role in uterine diseases such as fibroids and endometriosis. New studies provide a mechanism of action for estrogenic chemicals and other endocrine disrupters at the molecular level (called epigenetics) that may help explain the long-term effects of endocrine disruption.
PMID: 16522520 [PubMed – in process]
Am J Obstet Gynecol. 2006 Mar;194(3):755-9.
Elevated levels of fibroblast growth factor-2 in serum from women with endometriosis.
Bourlev V, Larsson A, Olovsson M.
Research Centre of Obstetrics, Gynaecology and Perinatology, Russian Academy of the Medical Sciences, Moscow, Russia.
OBJECTIVE: The purpose of this study was to determine whether serum and peritoneal fluid levels of fibroblast growth factor-2 (FGF-2) differ between women with and without endometriosis and to examine the relationship between proliferative activity in the endometriotic lesions and the levels of FGF-2 in serum and peritoneal fluid. STUDY DESIGN: Biopsy specimens of peritoneal endometriotic lesions (n = 25) were analyzed immunohistochemically regarding proliferative activity in stroma, glands, and blood vessels. The FGF-2 concentration was measured in peritoneal fluid and serum from 25 women with endometriosis and 14 healthy controls. RESULTS: Patients with endometriosis had higher serum concentrations of FGF-2 during both the proliferative and secretory menstrual phases than healthy women. Peritoneal fluid levels of FGF-2 differed significantly between women with high and low proliferative activity in their endometriotic lesions. CONCLUSION: Women with endometriosis have a higher serum level of FGF-2 than healthy controls.
PMID: 16522409 [PubMed – in process]
Acta Obstet Gynecol Scand. 2006;85(1):88-92.
Depression in women with endometriosis with and without chronic pelvic pain.
Lorencatto C, Petta CA, Navarro MJ, Bahamondes L, Matos A.
Department of Psychology, Women’s Hospital, Universidade Estadual de Campinas, Sao Paulo, Brazil.
AIM: The aim of the study is to compare the prevalence of depression in women surgically diagnosed with endometriosis according to the presence or absence of pelvic pain. METHODS: This cross-sectional prospective study evaluated 100 women receiving care at the Outpatients’ Clinic for Endometriosis, Department of Obstetrics and Gynecology, Universidade Estadual de Campinas (UNICAMP), Campinas, Sao Paulo, Brazil, equally divided into two groups: one suffering from chronic pelvic pain and the other pain-free. The Beck Depression Inventory was used in order to measure depression. RESULTS: Depression was detected in 86 and 38% of the women with and without chronic pelvic pain, respectively. Complaints of depression, such as somatic concerns, work inhibition, dissatisfaction, and sadness, were observed at a significantly higher rate in the group with pain. A sensation of failure was the only variable observed more frequently in the pain-free group. CONCLUSIONS: Depression is highly prevalent in women with endometriosis, especially those with pelvic pain. Careful evaluation can identify women with depression who may benefit from treatment.
PMID: 16521687 [PubMed – in process]
Pol Merkuriusz Lek. 2005 Dec;19(114):855-8.
[Perspectives of endometriosis treatment] [Article in Polish] Szyllo K, Gorski J, Tchorzewski H.
Instytut Centrum Zdrowia Matki Polki w Lodzi, Klinika Ginekologii Operacyjnej. kgoczmp@poczta.onet.pl
In recent years a dynamic development of research on endometriosis has been observed. Complex and not definitively recognized etiopathogenesis, impedes diagnostic progress and effective treatment. Frequent incidence of endometriosis in reproductive age and high percentage of the illness in the group of patients with infertility, both determine the importance of that issue. The article below presents the latest lines of research on efficient therapeutical scheme, covering reproductive abilities. Attempts of implementation of aromatase inhibitors, selective estrogen receptor modulators, immunomodulators and antiinflammatory agents have been described. Considering groups of medicines mentioned in the article, the outcome of examination using aromatase inhibitors, immunomodulators mainly IL-2, INF-alpha-2b, as well as antiinflammatory agents–recombinant human TNF binding protein-1, seem to be most encouraging. Part of the survey was conducted on animal models therefore it requires verification of usefulness and effectiveness on people. The results are very promising, they set the trend of future research aimed at application of modern and efficient treatment of endometriosis.
PMID: 16521440 [PubMed – in process]
Best Pract Res Clin Obstet Gynaecol. 2006 Mar 3; [Epub ahead of print] Adenomyosis and reproduction.
Leyendecker G, Kunz G, Kissler S, Wildt L.
Evidence has been provided that pelvic endometriosis is significantly associated with uterine adenomyosis and that the latter constitutes the major factor of infertility in such conditions. Furthermore, it has become evident that both adenomyosis and endometriosis constitute a pathophysiological and nosological entity. Mild peritoneal endometriosis of the fertile woman and premenopausal adenomyosis of the parous and non-parous woman, as well as adenomyosis in association with endometriosis of the infertile woman, constitute a pathophysiological continuum that is characterized by the dislocation of basal endometrium. Due to the postponement of childbearing late into the period of reproduction, premenopausal adenomyosis might increasingly become a factor for infertility in addition to adenomyosis associated with endometriosis of younger women. In any event, the presence or absence of uterine adenomyosis should be examined in a sterility work-up.
PMID: 16520094 [PubMed – as supplied by publisher]
Hum Reprod. 2006 Apr;21(4):870-9. Epub 2006 Mar 3.
Effects of combined 17beta-estradiol with TCDD on secretion of chemokine IL-8 and expression of its receptor CXCR1 in endometriotic focus-associated cells in co-culture.
Shi YL, Luo XZ, Zhu XY, Hua KQ, Zhu Y, Li DJ.
Laboratory for Reproductive Immunology, Hospital and Institute of Obstetrics and Gynecology, Shanghai Medical College, Fudan University, Shanghai 200011 Nanjing Maternity Child Health Hospital, Nanjing Medical University, Jiangsu 210004, China.
BACKGROUND: Chemokines play an important role in the pathogenesis of endometriosis. In the present study, the transcription of 18 chemokine receptors in eutopic endometrium and ectopic tissue with endometriosis was first analysed by RT-PCR. Dioxin, an air pollutant, and estrogen are reported to be associated with endometriosis. The regulatory mechanisms of dioxin and estrogen in the expression of CXCR1/IL-8 in the corresponding cells will help in elucidating roles of the chemokine in the aetiology of endometriosis. METHODS AND RESULTS: CXCR1, a type of chemokine receptor, was over-expressed in endometriotic tissue. The high translation of the receptor and its ligand, interleukin (IL-8), in endometriotic tissue was then demonstrated by immunochemistry. Estradiol and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) alone inhibited expression of CXCR1, whereas the combination of estradiol with TCDD up-regulated the expression. TCDD promoted IL-8 secretion by human pelvic mesothelial cells (HPMC), and 17beta-estradiol magnified the stimulatory effect. Both 17beta-estradiol and TCDD alone inhibited IL-8 secretion of U937 (a cell line of monocyte), but combination of 17beta-estradiol and TCDD had no further inhibitory effect. The co-culture of endometrial stromal cells (ESC) with HPMC produced more IL-8 than respective or total production of either of the cells alone, and estradiol played a synergistic stimulatory role with TCDD in IL-8 secretion of the co-culture. Interaction of HPMC and the monocytes significantly stimulated IL-8 secretion, suggesting a main resource of IL-8 in peritoneal cavity with endometriosis. TCDD promoted IL-8 secretion by HPMC-U937 co-culture, but exerted a contrary effect for IL-8 secretion when combined with estradiol. CONCLUSION: Estradiol and TCDD in the peritoneal cavity can lead to a persistent and serious inflammation, which gives a new insight into the interactions of estrogen and TCDD in endometriosis.
PMID: 16517565 [PubMed – in process]
Hum Reprod. 2006 Mar 3; [Epub ahead of print] Treatment with anti-TNF monoclonal antibody (c5N) reduces the extent of induced endometriosis in the baboon.
Falconer H, Mwenda JM, Chai DC, Wagner C, Song XY, Mihalyi A, Simsa P, Kyama C, Cornillie FJ, Bergqvist A, Fried G, D’Hooghe TM.
Department of Obstetrics and Gynaecology, Karolinska Hospital, Stockholm, Sweden.
BACKGROUND: Inflammatory cytokines, including interleukin (IL)-1, IL-6, IL-8 and tumour necrosis factor-alpha (TNF-alpha), are important in the pathogenesis of endometriosis. We assessed the efficacy of anti-TNF monoclonal antibody (mAb, c5N), known to prevent induced endometriosis in baboons, in reducing established endometriosis in baboons. METHODS: This prospective, randomized, blinded, controlled study was conducted in baboons at the Institute of Primate Research (IPR), Nairobi, Kenya. Endometriosis was induced in 18 adult female baboons (Papio anubis) with regular menstrual cycles and a normal pelvis; the extent of endometriosis was documented by video-laparoscopy 25 days later. The baboons were then randomly assigned to receive a single infusion of either placebo (n = 7, 5 ml/kg) or c5N (n = 11, 5 mg/kg). Follow-up laparoscopy was performed 25 days later to document any differences in the number, surface area and estimated volume of lesions between the two groups and between the first and the second laparoscopies in each group. Representative biopsies of at least one endometriotic lesion per baboon were obtained at the final laparoscopy. RESULTS: Significant reductions in total surface area, estimated total volume of endometriotic lesions and both number and surface area of red lesions were observed after treatment with c5N, but not after placebo treatment, when compared to the initial laparoscopy. Conversely, a significant increase in the number of typical and red lesions was observed after placebo treatment when compared to the initial laparoscopy. Neither c5N nor placebo treatment affected the menstrual cycle. CONCLUSION: In baboons with induced endome-triosis, anti-TNF-mAb (c5N) treatment significantly reduced the extent of endometriosis, mainly due to reducing both the number and surface area of red lesions. These findings suggest that anti-TNF-mAb therapy may have therapeutic potential for active peritoneal endometriosis.
PMID: 16517562 [PubMed – as supplied by publisher]

Best Pract Res Clin Obstet Gynaecol. 2006 Feb 28; [Epub ahead of print] History of adenomyosis.
Benagiano G, Brosens I.
Department of Gynaecological Sciences, Perinatology and Child Care, University ‘la Sapienza’, Rome, Italy; Leuven Institute for Fertility and Embryology, Leuven, Belgium.
Although the claim has been made that there are early descriptions of what today we call endometriosis and adenomyosis in theses presented in Europe in the late 17(th) and during the 18(th) centuries, the first description of the condition initially named ‘adenomyoma’ is that provided in 1860 by the German pathologist Carl von Rokitansky, who found endometrial glands in the myometrium and designated this finding as ‘cystosarcoma adenoids uterinum’. Over the following 50 years ‘adenomyoma’ (and endometriosis) were considered pathologies separate from the so-called ‘haemorrhagic ovarian cysts’, and it was not until 1921 that this condition was recognized to be of endometriotic origin. The first systematic description of what is today known as adenomyosis was the work of Thomas Stephen Cullen who, at the turn of the 19(th) century, fully researched the ‘mucosal invasion’ already observed by a number of investigators in several parts of the lower abdominal cavity. Cullen clearly identified the epithelial tissue invasion as being made of ‘uterine mucosa’ and defined the mechanism through which the mucosa invades the underlying tissue. In 1925, 2 years before Sampson created the term ‘endometriosis’, Frankl created a name for the mucosal invasion of the myometrium and clearly described its anatomical picture; he called it ‘adenomyosis uteri’ and explained that ‘I have chosen the name of adenomyosis, which does not suggest any inflammatory genesis as do terms like adenometritis, adenomyositis, adenomyometritis, still employed’. The current definition of adenomyosis was finally provided in 1972 by Bird who stated: ‘Adenomyosis may be defined as the benign invasion of endometrium into the myometrium, producing a diffusely enlarged uterus which microscopically exhibits ectopic non-neoplastic, endometrial glands and stroma surrounded by the hypertrophic and hyperplastic myometrium’.
PMID: 16515887 [PubMed – as supplied by publisher]
J Br Menopause Soc. 2006 Mar;12(1):28-33.
Managing women with a previous diagnosis of endometriosis.
Bain C.
Gynaecology Department, Aberdeen Royal Infirmary, Aberdeen, UK. christine.bain@nhs.net
Endometriosis is an estrogen-dependent condition that primarily inflicts women of reproductive age. There are several gradations of the disease and its extent does not always signify its symptomatic presentation. In those women who have long suffered from endometriosis, previous treatments and their assumed success influence clinical decision making on the use of hormone replacement therapy after menopause. This review considers the management strategies for those women who have become prematurely menopausal after extensive surgical treatment for endometriosis.
PMID: 16513020 [PubMed – in process]
Ter Arkh. 2006;78(1):52-7.
[Free radical processes in patients with iron deficiency anemia treated with iron medication] [Article in Russian] Dvoretskii LI, Zaspa EA, Litvitskii PF, Bolevich SB, Men’shova NI.
AIM: To study the effects of iron salts drugs (ISD) sorbifer durules and ferro-folgamma on free radical processes in 44 patients with iron deficiency anemia (IDA). MATERIAL AND METHODS: IDA was diagnosed as a rule in women with uterine myomas, endometriosis, dysfunctional hemorrhage and other menorragias. Generation of active oxygen forms (AOF) was estimated by hemoluminescence (CL) before and after therapy. Lipid peroxidation was assessed by malonic dialdehyde (MDA) in plasma, antiperoxide plasma activity (APA)–by CL intensity in interaction with nitric peroxide. The system of antioxidant defense in ISD treatment was estimated by the activity of key antioxidant enzymes: superoxidedismutase, glutathion peroxidase and catalase. RESULTS: The studied ISD normalized hemoglobin 3-4 weeks after the treatment onset. MDA decreased. Generation of AOF and activity of plasmic antioxidant enzymes did not change much. CONCLUSION: ISD modulate free radical processes without oxidant stress.
PMID: 16512446 [PubMed – indexed for MEDLINE]
J Clin Invest. 2006 Mar;116(3):561-70.
Estrogen receptors and human disease.
Deroo BJ, Korach KS.
Receptor Biology Section, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, North Carolina 27709, USA.
Estrogens influence many physiological processes in mammals, including but not limited to reproduction, cardiovascular health, bone integrity, cognition, and behavior. Given this widespread role for estrogen in human physiology, it is not surprising that estrogen is also implicated in the development or progression of numerous diseases, which include but are not limited to various types of cancer (breast, ovarian, colorectal, prostate, endometrial), osteoporosis, neurodegenerative diseases, cardiovascular disease, insulin resistance, lupus erythematosus, endometriosis, and obesity. In many of these diseases, estrogen mediates its effects through the estrogen receptor (ER), which serves as the basis for many therapeutic interventions. This Review will describe diseases in which estrogen, through the ER, plays a role in the development or severity of disease.
PMID: 16511588 [PubMed – in process]

Obstet Gynecol. 2006 Mar;107(3):595-604.
Ectopic Pregnancy Risk With Assisted Reproductive Technology Procedures.
Clayton HB, Schieve LA, Peterson HB, Jamieson DJ, Reynolds MA, Wright VC.
Division of Reproductive Health, National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention, Atlanta, Georgia; and Departments of Maternal and Child Health and Obstetrics and Gynecology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
OBJECTIVE: To assess the ectopic pregnancy risk among women who conceived with assisted reproductive technology (ART) procedures. METHODS: The ectopic rate for ART pregnancies was calculated from population-based data of pregnancies conceived with ART in U.S. clinics in 1999-2001. Variation in ectopic risk by patient and ART treatment factors was assessed by using bivariate analyses and multivariable logistic regression. RESULTS: Of 94,118 ART pregnancies, 2,009 (2.1%) were ectopic. Variation was observed by procedure type. In comparison with the ectopic rate (2.2%) among pregnancies conceived with in vitro fertilization and transcervical transfer of freshly fertilized embryos from the patient’s oocytes (fresh, nondonor IVF-ET), the ectopic rate was significantly increased when zygote intrafallopian transfer (ZIFT) was used (3.6%) and significantly decreased when donor oocytes were used (1.4%) or when a gestational surrogate carried the pregnancy (0.9%). Among fresh nondonor IVF-ET procedures, the risk for ectopic pregnancy was increased among women with tubal factor infertility (odds ratio [OR] 2.0, 95% confidence interval [CI] 1.7-2.4; referent group = ART for male factor), endometriosis (OR 1.3, 95% CI 1.0-1.6), and other nontubal female factors of infertility (OR 1.4, 95% CI 1.2-1.6) and decreased among women with a previous live birth (OR 0.6, 95% CI 0.5-0.7). Transfer of embryos with an indication of high implantation potential was associated with a decreased ectopic risk when 2 or fewer embryos were transferred (OR 0.7, 95% CI 0.5-0.9), but not when 3 or more embryos were transferred. CONCLUSION: Ectopic risk among ART pregnancies varied according to ART procedure type, reproductive health characteristics of the woman carrying the pregnancy, and estimated embryo implantation potential. LEVEL OF EVIDENCE: II-2.
PMID: 16507930 [PubMed – as supplied by publisher]

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