Pag. 15

Cochrane Database Syst Rev.2012 Mar 14;3:CD002122.

Progestagens and anti-progestagens for pain associated with endometriosis.

Brown J, Kives S, Akhtar M.

Source

Obstetrics and Gynaecology, University of Auckland, FMHS, Auckland, New Zealand.

Abstract

BACKGROUND:

Endometriosis is a chronic inflammatory condition defined by the presence of glands and stroma outside the uterine cavity. It occurs in 7% to 10% of all women of reproductive age and may present as pain or infertility. The pelvic pain may be in the form of dysmenorrhoea, dyspareunia or pelvic pain. Initially a combination of estrogens and progestagens was used to create a pseudopregnancy and alleviate the symptoms associated with endometriosis. Progestagens alone or anti-progestagens have been considered as alternatives because they are inexpensive and may have a better side effect profile than other choices.

OBJECTIVES:

To determine the effectiveness of both the progestagens and anti-progestagens in the treatment of painful symptoms ascribed to the diagnosis of endometriosis.

SEARCH METHODS:

We used the search strategy of the Menstrual Disorders and Subfertility Group to identify all publications which described or might have described randomised controlled trials (RCTs) of any progestagen or any anti-progestagen in the treatment of symptomatic endometriosis. We updated the review in 2011.

SELECTION CRITERIA:

We considered only RCTs which compared the use of progestagens and anti-progestagens with other interventions, placebo or no treatment for the alleviation of symptomatic endometriosis.

DATA COLLECTION AND ANALYSIS:

We have added six new studies, bringing the total of included studies to 13 in the update of this review. The six newly included studies evaluated progestagens (comparisons with placebo, danazol, oral or subdermal contraceptive, oral contraceptive pill and danazol, gonadotrophin-releasing hormone (GnRH) analogue and other drugs). The remaining studies compared the anti-progestagen gestrinone with danazol, GnRH analogues or itself.

MAIN RESULTS:

The progestagen medroxyprogesterone acetate (100 mg daily) appeared to be more effective at reducing all symptoms up to 12 months of follow-up (MD -0.70, 95% CI -8.61 to -5.39; P < 0.00001) compared with placebo. There was evidence of significantly more cases of acne (six versus one) and oedema (11 versus one) in the medroxyprogesterone acetate group compared with placebo. There was no evidence of a difference in objective efficacy between dydrogesterone and placebo.There was no evidence of a benefit with depot administration of progestagens versus other treatments (low dose oral contraceptive or leuprolide acetate) for reduced symptoms. The depot progestagen group experienced significantly more adverse effects.There was no overall evidence of a benefit of oral progestagens over other medical treatment at six months of follow-up for self-reported efficacy. Amenorrhoea and bleeding were more frequently reported in the progestagen group compared with other treatment groups.There was no evidence of a benefit of anti-progestagens (gestrinone) compared with danazol. GnRH analogue (leuprorelin) was found to significantly improve dysmenorrhoea compared with gestrinone (MD 0.82, 95% CI 0.15 to 1.49; P = 0.02) although it was also associated with increased hot flushes (OR 0.20, 95% CI 0.06 to -0.63; P = 0.006).

AUTHORS’ CONCLUSIONS:

There is only limited evidence to support the use of progestagens and anti-progestagens for pain associated with endometriosis.

Update of

• Cochrane Database Syst Rev. 2000;(2):CD002122.

Br J Cancer.2012 Mar 13;106(6):1205-13. doi: 10.1038/bjc.2012.26. Epub 2012 Feb 21.

Creation of immortalised epithelial cells from ovarian endometrioma.

Bono Y, Kyo S, Takakura M, Maida Y, Mizumoto Y, Nakamura M, Nomura K, Kiyono T, Inoue M.

Source

Department of Obstetrics and Gynecology, Kanazawa University Graduate School of Medical Science, 13-1 Takaramachi, Kanazawa, Ishikawa 920-8641, Japan.

Abstract

BACKGROUND:

Epithelial cells of endometriotic tissues are difficult to propagate in vitro as experimental material is scarce owing to their limited life span. However, there is an increasing concern regarding their malignant transformation in ovaries. The present study sought to generate their stable culture system.

METHODS AND RESULTS:

Purified epithelial cells isolated from ovarian endometriomas using microscopic manipulation were successfully immortalised by combinatorial transfection of human cyclinD1, cdk4 and human telomerase reverse transcriptase (hTERT) genes, whereas the introduction of hTERT alone, or together with cdk4, was insufficient for immortalisation, leading to cellular senescence. We confirmed stable cytokeratin expression in the immortalised cells, proving their epithelial origin. These cells expressed progesterone receptor B and showed significant growth inhibition by various progestins. Oestrogen receptor (ER) expression was detected in these cells, albeit at low levels. Additional overexpression of ERα generated stable cells with oestrogen-dependent growth activation. Soft-agar colony formation assay and nude mice xenograft experiments demonstrated that these cells, even those with additional inactivation of p53, did not have transformed phenotypes.

CONCLUSION:

We for the first time generated immortalised epithelial cells from ovarian endometrioma that retained sex steroid responsiveness. These cells are invaluable tools not only for the consistent in vitro work but also for the study of molecular pathogenesis or carcinogenesis of endometriosis.

Nat Rev Clin Oncol.2012 Mar 13;9(4):189. doi: 10.1038/nrclinonc.2012.31.

Gynecological cancer: Endometriosis link to invasive subtypes.

Ozerlat I.

Comment on

• Association between endometriosis and risk of histological subtypes of ovarian cancer: a pooled analysis of case-control studies.[Lancet Oncol. 2012]

Surg Endosc.2012 Mar 10. [Epub ahead of print]

Combined transurethral approach with Versapoint(®) and laparoscopic treatment in the management of bladder endometriosis: technique and 12 months follow-up.

Litta P, Saccardi C, D’Agostino G, Florio P, De Zorzi L, Bianco MD.

Source

Department of Gynecological Sciences and Human Reproduction, University of Padova, Via Giustiniani 3, 35128, Padua, Italy.

Abstract

BACKGROUND:

When endometriosis infiltrates more than 5 mm beneath the peritoneum it is called deeply infiltrating endometriosis and may involve the bladder. Only 1-2% of women with endometriosis have urinary involvement, mainly in the bladder. Resectoscopic transurethral resection alone is no longer recommended because of the surgical risks and recurrence. Usually surgeons prefer a laparotomy or laparoscopic approach depending on nodule localization and personal skill. We describe a new combined transurethral approach with Versapoint(®) and laparoscopic technique in the management of bladder endometriosis and the 12-month follow-up.

METHODS:

We performed a prospective observational study of 12 women affected by symptomatic bladder endometriosis at the University Hospital of Padova. We utilized a transurethral approach using a 5.2-mm endoscope with a 0.6-mm-diameter bipolar electrode (Gynecare Versapoint(®)). We delimited just the edges of the lesion via cystoscopy, penetrating transmurally at 3 or 9 o’clock without trespassing into the bladder peritoneum. Then, starting from the lateral bladder hole, we excised the lesion by laparoscopy with Harmonic ACE(®). The bladder hole was repaired with a continuous 3-0 monofilament two-layer suture.

RESULTS:

Operating time ranged from 115 to 167 min and mean blood loss ranged from 10 to 200 ml. No conversion to laparotomy and no intraoperative complications occurred. No dysuria or hematuria were present at follow-up. There was one case of persistent suprapubic pelvic pain at the 12-month follow-up.

CONCLUSIONS:

A combined transurethral approach with Versapoint(®) and laparoscopic treatment is a safe and easy technique for the management of bladder endometriosis, with low risks and good resolution of symptoms.

Int Urogynecol J.2012 Mar 8. [Epub ahead of print]

Diagnosis of interstitial cystitis/bladder pain syndrome in women with chronic pelvic pain: a prospective observational study.

Cheng C, Rosamilia A, Healey M.

Source

Royal Women’s Hospital, 20 Flemington Road, Parkville, VIC, 3052, Australia, claudiacheng@drclaudiacheng.com.au.

Abstract

INTRODUCTION AND HYPOTHESIS:

This study assesses the prevalence of interstitial cystitis (IC)/bladder pain syndrome (BPS) in women with chronic pelvic pain (CPP).

METHODS:

This was a prospective study of 150 women undergoing laparoscopy as investigation for CPP in an Endometriosis and Pelvic Pain unit. Preoperative questionnaires [demographic details, pelvic pain symptoms, the Pelvic Pain and Urgency/Frequency (PUF) and O’Leary-Sant (OLS) Symptom and Problem Index scores] were completed, and concurrent standardized cystoscopy with hydrodistention performed at laparoscopy. The primary outcome measures the proportion of IC in this group, defined by presence of glomerulations with CPP and urinary symptoms (urinary frequency, nocturia, urgency). The secondary outcome measures the proportion of BPS [defined by the European Society of the Study of Interstitial Cystitis (ESSIC)].

RESULTS:

IC was diagnosed in 48/150 (32%) individuals, and 80/150 (53%) had BPS. There were no significant differences in symptomatology or questionnaire results between groups with and without IC. Women with BPS had higher PUF (17.2 vs 12.9, p < 0.001), OLS Symptom (8.2 vs 6.0, p = 0.001) and Problem (7.5 vs 4.2, p < 0.001) scores and more severe pain symptoms. Visually proven endometriosis was seen in 90/150 (60%), and 27/150 (18%) had both endometriosis and IC. Of the 80 women with BPS, 45/80 (60%) had endometriosis.

CONCLUSIONS:

The prevalence of IC/BPS varies depending on the definition used. This study showed IC in 32% of women with CPP based on symptoms and presence of glomerulations. BPS as defined by ESSIC was diagnosed in 53%. History and questionnaires did not correlate with positive cystoscopic findings.

Fertil Steril.2012 Mar 3. [Epub ahead of print]

Risks of adverse pregnancy outcome in endometriosis.

Brosens I, Brosens JJ, Fusi L, Al-Sabbagh M, Kuroda K, Benagiano G.

Source

Leuven Institute of Fertility and Embryology, Leuven, Belgium.

Abstract

Bleeding from endometriotic implants is now an established cause of acute hemoperitoneum in pregnancy. However, the adverse impact of pelvic endometriosis on uterine function before conception may also interfere with subsequent deep placentation, accounting for the increased risk of obstetrical complications, including preterm birth and antepartum hemorrhage.

Acta Obstet Gynecol Scand.2012 Mar;91(3):338-45. doi: 10.1111/j.1600-0412.2011.01346.x. Epub 2012 Jan 26.

Randomized comparison of superovulation with letrozole vs. clomiphene citrate in an IUI program for women with recently surgically treated minimal to mild endometriosis.

Abu Hashim H, El Rakhawy M, Abd Elaal I.

Source

Department of Obstetrics & Gynecology, Mansoura Faculty of Medicine, Mansoura University, Egypt. hatem_ah@hotmail.com

Abstract

OBJECTIVE:

To evaluate pregnancy rates with letrozole and clomiphene citrate (CC) alone for superovulation in an intrauterine insemination program for women with recently surgically treated minimal to mild endometriosis.

DESIGN:

A randomized controlled trial following the CONSORT criteria.

SETTING:

University teaching hospital and a private practice setting.

PATIENTS:

136 women with primary infertility due to minimal to mild endometriosis who did not achieve pregnancy after six to 12 months following laparoscopic treatment.

INTERVENTIONS:

Superovulation using 5 mg letrozole/day (69 women, 220 cycles) or 100 mg CC/day (67 women, 213 cycles) for five days combined with intrauterine insemination up to four cycles.

MAIN OUTCOME MEASURES:

Clinical pregnancy rate per cycle, cumulative pregnancy rate after four cycles, number of follicles, serum estradiol, endometrial thickness on the day of human chorionic gonadotropin administration, serum progesterone, miscarriage and live birth rates.

RESULTS:

The clinical pregnancy rate per cycle and the cumulative pregnancy rate after four cycles were comparable (15.9 vs. 14.5% and 64.7 vs. 57.2%; p=0.82, p=0.71 in letrozole and CC groups, respectively). Two twin pregnancies occurred in the CC/intrauterine insemination group. Miscarriage and live birth rates were comparable (11.4 vs. 12.9% and 44.9 vs. 40.3%; p=0.47, p=0.62 in letrozole and CC groups, respectively). The total number of follicles and serum estradiol on the day of human chorionic gonadotropin administration were significantly increased in the CC group.

CONCLUSIONS:

Superovulation with letrozole is not more effective than clomiphene citrate alone in an intrauterine insemination program for women with minimal to mild endometriosis who did not achieve pregnancy after six to 12 months following laparoscopic treatment. ClinicalTrials.gov ID: NCT01334762.

© 2012 The Authors Acta Obstetricia et Gynecologica Scandinavica© 2012 Nordic Federation of Societies of Obstetrics and Gynecology.

Am J Pathol.2012 Mar;180(3):880-7. Epub 2011 Dec 30.

Host-derived TGFB1 deficiency suppresses lesion development in a mouse model of endometriosis.

Hull ML, Johan MZ, Hodge WL, Robertson SA, Ingman WV.

Source

The Robinson Institute, Research Centre for Reproductive Health, and School of Paediatrics and Reproductive Health, University of Adelaide, Adelaide, Australia. louise.hull@adelaide.edu.au

Abstract

Transforming growth factor-β1 (TGFB1) is a multifunctional cytokine that is abundant in both endometriotic lesions and the peritoneal fluid in women with endometriosis. However, the role of TGFB1 in the development of endometriosis is as yet undefined. In the present study, we investigated the physiologic function of TGFB1 in endometriotic lesion development, using Tgfb1-null mutant mice on a background of severe combined immunodeficiency. Xenotransplantation of human eutopic endometrial tissue resulted in development of endometriosis-like lesions in 63% of ovariectomized estrogen-supplemented Tgfb1-null mutant mice and in 68% of wild-type control mice. Median lesion weight was reduced by 11-fold in Tgfb1-null mice compared with wild-type control mice, and the fraction of glandular epithelium in lesions from Tgfb1-null mice was reduced by 32% compared with that in control mice. In lesions from Tgfb1-null mice, the relative abundance of both macrophages and α-smooth muscle actin-positive myofibroblasts was reduced by 66% and 47%, respectively. Deficiency of TGFB1 neither altered the percentage of proliferating cells in the epithelial or stromal compartments of the lesions nor affected blood vessel density or vessel size. Observation of this study indicates that host-derived TGFB1 deficiency suppresses endometriotic lesion development and provides proof of principle that targeting TGFB1 signaling pathways in cells that support the survival of ectopic endometrium may be an effective therapeutic approach in women with endometriosis.

Bioorg Med Chem Lett.2012 Mar 1;22(5):1860-3. Epub 2012 Jan 28.

New aromatase inhibitors from the 3-pyridyl arylether and 1-aryl pyrrolo [2,3-c]pyridine series.

Stauffer F, Furet P, Floersheimer A, Lang M.

Source

Novartis Institutes for BioMedical Research, Global Discovery Chemistry Oncology, Postfach, CH-4002 Basel, Switzerland. frederic.stauffer@novartis.com

Abstract

Aromatase inhibition is the new standard of care for estrogen receptor positive breast cancer and has also potential for treatment of other diseases such as endometriosis. Simple and readily available 3-pyridyl arylethers and 1-aryl pyrrolo[2,3-c]pyridines recapitulating the key pharmacophore elements of Letrozole (1) are described and their structure-activity relationships are discussed. Potent and ligand efficient leads such as compound 23 (IC(50)=59nM on aromatase) have been identified.

Curr Obstet Gynecol Rep.2012 Mar;1(1):1-9.

Ovarian Cancer Is an Imported Disease: Fact or Fiction?

Kuhn E, Kurman RJ, Shih IM.

Source

Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD 21231, USA.

Abstract

The cell of origin of ovarian cancer has been long debated. The current paradigm is that epithelial ovarian cancer (EOC) arises from the ovarian surface epithelium (OSE). OSE is composed of flat, nondescript cells more closely resembling the mesothelium lining the peritoneal cavity, with which it is continuous, rather than the various histologic types of ovarian carcinoma (serous, endometrioid, and clear cell carcinoma), which have a Müllerian phenotype. Accordingly, it has been argued that the OSE undergoes a process termed “metaplasia” to account for this profound morphologic transformation. Recent molecular and clinicopathologic studies not only have failed to support this hypothesis but also have provided evidence that EOC stems from Müllerian-derived extraovarian cells that involve the ovary secondarily, thereby calling into question the very existence of primary EOC. This new model of ovarian carcinogenesis proposes that fallopian tube epithelium (benign or malignant) implants on the ovary to give rise to both high-grade and low-grade serous carcinomas, and that endometrial tissue implants on the ovary and produces endometriosis, which can undergo malignant transformation into endometrioid and clear cell carcinoma. Thus, ultimately EOC is not ovarian in origin but rather is secondary, and it is logical to conclude that the only true primary ovarian neoplasms are germ cell and gonadal stromal tumors analogous to tumors in the testis. If this new model is confirmed, it has profound implications for the early detection and treatment of “ovarian cancer.”

DNA Cell Biol.2012 Mar;31(3):317-22. Epub 2011 Aug 17.

Mitochondria DNA polymorphisms are associated with susceptibility to endometriosis.

Cho S, Lee YM, Choi YS, Yang HI, Jeon YE, Lee KE, Lim K, Kim HY, Seo SK, Lee BS.

Source

Department of Obstetrics and Gynecology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.

Abstract

Because energy production involves oxidative phosphorylation, mitochondria are major sources of reactive oxygen species in the cell. Recent findings indicate that mitochondrial DNA (mtDNA) variants may play a role in the etiology of certain autoimmune and chronic inflammatory diseases. The aim of this study was to investigate the possible association between mtDNA polymorphisms and susceptibility to endometriosis. This study included 198 patients with histologically confirmed endometriosis and 167 patients without endometriosis as controls. Common variants of mtDNA at nt10398 (A/G transition), nt13708 (G/A transition), and nt16189 (T/C transition) were detected using polymerase chain reaction. An association study was performed with a chi-square test and logistic regression analysis. The prevalence of the mtDNA nt16189 variant was higher in patients with endometriosis (46.0%, 91 of 198) than in controls (34.7%, 58 of 167) (p=0.030) with odds ratio (OR) of 1.98 (95% confidence interval [CI]: 1.04-3.78). A combination of the 10398 and 16189 variants was also associated with increased risk for endometriosis (OR=1.90, 95% CI: 1.13-3.18, p=0.015). These associations remained significant even after adjusting for age and body mass index. Our data strongly suggest that the mtDNA 16189 variants and the combination of mtDNA 16189 and 10398 variants increase susceptibility to endometriosis.

EMBO Mol Med.2012 Mar;4(3):206-17. doi: 10.1002/emmm.201100200. Epub 2012 Feb 3.

A polymorphism in a let-7 microRNA binding site of KRAS in women with endometriosis.

Grechukhina O, Petracco R, Popkhadze S, Massasa E, Paranjape T, Chan E, Flores I, Weidhaas JB, Taylor HS.

Source

Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, CT, USA.

Abstract

Endometriosis is found in 5-15% of women of reproductive age and is more frequent in relatives of women with the disease. Activation of KRAS results in de novo endometriosis in mice, however, activating KRAS mutations have not been identified in women. We screened 150 women with endometriosis for a polymorphism in a let-7 microRNA (miRNA) binding site in the 3′-UTR of KRAS and detected a KRAS variant allele in 31% of women with endometriosis as opposed to 5% of a large diverse control population. KRAS mRNA and protein expression were increased in cultured endometrial stromal cells of women with the KRAS variant. Increased KRAS protein was due to altered miRNA binding as demonstrated in reporter assays. Endometrial stromal cells from women with the KRAS variant showed increased proliferation and invasion. In a murine model, endometrial xenografts containing the KRAS variant demonstrated increased proliferation and decreased progesterone receptor levels. These findings suggest that an inherited polymorphism of a let-7 miRNA binding site in KRAS leads to abnormal endometrial growth and endometriosis. The LCS6 polymorphism is the first described genetic marker of endometriosis risk.

Eur J Obstet Gynecol Reprod Biol.2012 Mar;161(1):42-5. Epub 2011 Dec 24.

Essure® hydrosalpinx occlusion prior to IVF-ET as an alternative to laparoscopic salpingectomy.

Mijatovic V, Dreyer K, Emanuel MH, Schats R, Hompes PG.

Source

VU University Medical Center, Department of Reproductive Medicine, Amsterdam, The Netherlands. mijatovic@vumc.nl

Abstract

OBJECTIVE:

To investigate the success rate of proximal tubal occlusion with Essure(®) devices in subfertile women with unilateral or bilateral hydrosalpinx and to observe the results of subsequent treatment with IVF-ET and/or frozen embryo transfer.

STUDY DESIGN:

Prospective, single-arm, clinical study in 20 women with unilateral or bilateral hydrosalpinges (all visible on transvaginal ultrasound) due to undergo IVF-ET and/or frozen embryo transfer. In all patients, laparoscopy was considered to be contraindicated due to extensive pelvic adhesions.

RESULT(S):

In all patients the Essure(®) devices were placed in an ambulant setting without any complications. Proximal tubal occlusion was confirmed by hysterosalpingography in 19 out of 20 patients (95%) and in 26 of 27 treated tubes (96%). After 45 embryo transfer procedures in 19 patients, 18 pregnancies with 12 live births, 6 miscarriages and 1 immature delivery (probably related to cervical insufficiency leading to chorioamnionitis and subsequent rupture of the membranes) were observed.

CONCLUSION(S):

Essure(®) devices are effective in inducing proximal tubal occlusion in subfertile patients with hydrosalpinges. After artificial reproductive treatments a cumulative live birth rate per patient of 63% and a cumulative live birth rate per transfer of 27% were achieved. The latter was related to the large proportion of patients with severe endometriosis.

Expert Opin Ther Targets.2012 Mar;16(3):237-41. Epub 2012 Feb 14.

Mast cells in endometriosis: guilty or innocent bystanders?

Kirchhoff D, Kaulfuss S, Fuhrmann U, Maurer M, Zollner TM.

Source

Bayer Pharma AG, GDD-Target Discovery, Muellerstr. 178, 13342 Berlin, Germany. dennis.kirchhoff@bayer.com

Abstract

Endometriosis (EMS) is a chronic, estrogen-dependent inflammatory disease characterized by growth of endometrial tissue outside the uterine cavity. Symptoms in EMS patients include severe pelvic pain, dysmenorrhea, dyspareunia and infertility. To date, medical therapies are mostly based on hormonal suppressive drugs that induce a hypoestrogenic state. Although being effective regarding the reduction of endometriotic tissue masses and pelvic pain, this treatment is accompanied by severe side effects. Since EMS is associated with chronic inflammation, novel therapeutic strategies also focus on immune modulating drugs. However, little is known about how and to what extent immune cell subsets contribute to the network of locally produced cytokines, chemokines and other mitogenic factors that modulate the growth of ectopic endometrial implants and the inflammation associated with them. Mast cells (MCs) are known to be key players of the immune system, especially during allergic reactions. However, in recent years MCs have been identified to exhibit a far broader range of functions and to be involved in host defense and wound healing responses. Here, recent reports that imply an involvement of MCs in EMS has been reviewed, while the value of novel mouse models for clarifying their contribution to the pathology of this condition has been discussed.

Fertil Steril.2012 Mar;97(3):771-8.e1. Epub 2012 Jan 21.

Adiponectin and leptin systems in human endometrium during window of implantation.

Dos Santos E, Serazin V, Morvan C, Torre A, Wainer R, de Mazancourt P, Dieudonné MN.

Source

Service de Biochimie et Biologie Moléculaire, Unité Propre de Recherche et de l’Enseignement Supérieur- Equipe d’Accueil 2493, Pôle de Recherche et de l’Enseignement Supérieur Universud Paris, Centre Hospitalier de Poissy-Saint Germain, Poissy Cedex, France. dossantos.esther@orange.fr

Abstract

OBJECTIVE:

To measure the expression of adiponectin, leptin, and their respective receptors in the human endometria of fertile women compared with women with unexplained recurrent implantation failure (IF) during the window of implantation.

DESIGN:

Controlled, prospective, clinical study.

SETTING:

Teaching hospital and university research laboratory.

PATIENT(S):

Thirty-one endometrial biopsies from women with IF and 19 fertile controls.

INTERVENTION(S):

Human endometrial biopsies.

MAIN OUTCOME MEASURE(S):

Gene and protein expression of endometrial biopsies.

RESULT(S):

Endometrial leptin expression was significantly lower in the IF group compared with fertile women. In contrast, leptin receptor (Ob-R) expression was higher in endometria of women with IF. Concerning the adiponectin system, adiponectin was expressed to the same extent in both groups. Conversely, the expression of its two receptors, AdipoR1 and AdipoR2, was reduced in endometria of women with IF compared with fertile women.

CONCLUSION(S):

Although progesterone resistance seems to be a common state of the endometrium in some human reproductive disorders, such as endometriosis or polycystic ovary syndrome, modification in leptin endometrial expression seems to be specific to IF. These results strongly suggest that changes in Ob-R and AdipoR expression profiles [1] should be implicated in the development of uterine receptivity, and [2] may therefore be potential new targets for prediction of IF.

Fertil Steril.2012 Mar;97(3):652-6. Epub 2012 Jan 18.

Does colorectal endometriosis alter intestinal functions? A prospective manometric and questionnaire-based study.

Mabrouk M, Ferrini G, Montanari G, Di Donato N, Raimondo D, Stanghellini V, Corinaldesi R, Seracchioli R.

Source

Minimally Invasive Gynaecological Surgery Unit, S. Orsola Hospital, University of Bologna, Bologna, Italy.

Abstract

OBJECTIVE:

To objectively evaluate using anorectal manometry whether endometriotic nodules influence intestinal function and to reveal subjective intestinal dysfunctions in patients with rectosigmoid deep infiltrating endometriosis.

DESIGN:

Prospective study.

SETTING:

Tertiary care university hospital.

PATIENT(S):

Patients (n = 25) with a preoperative diagnosis of rectosigmoid endometriosis.

INTERVENTION(S):

Patients underwent anorectal manometry; after that, they filled a questionnaire about defecatory functions and ranked their pain symptoms.

MAIN OUTCOME MEASURE(S):

The parameters studied were resting pressure, maximum squeezing pressure, pushing, rectoanal inhibitory reflex, and rectal sensibility. We analyzed the responses to the defecatory function questionnaire and the scored the endometriosis pain symptoms using a Visual Analogue Scale.

RESULT(S):

No alterations of the rectoanal inhibitory reflex were found. Hypertone of the internal anal sphincter was found in 20 of 25 patients. Almost half of the patients had an increase of the threshold of desire to defecate, and 7 patients had a reduction of the anal sphincter squeeze pressure. According to the responses to the defecatory function questionnaire, incomplete evacuation was the most common symptom.

CONCLUSION(S):

We did not find marked motility or sensitive dysfunctions at the anorectal manometry, whereas subjectively patients reported some defecatory disorders. We revealed the presence of hypertone of the internal anal sphincter in most of the patients. CLINICAL TRIAL REGISTRATION NUMBER: 74/2010/O/Sper.

Fertil Steril.2012 Mar;97(3):645-51. Epub 2011 Dec 22.

Physiologic activation of nuclear factor kappa-B in the endometrium during the menstrual cycle is altered in endometriosis patients.

González-Ramos R, Rocco J, Rojas C, Sovino H, Poch A, Kohen P, Alvarado-Díaz C, Devoto L.

Source

Departamento de Obstetricia y Ginecología, Instituto de Investigaciones Materno Infantil, Hospital San Borja-Arriarán, Facultad de Medicina, Universidad de Chile, Santiago, Chile. rgonzalezr@med.uchile.cl

Abstract

OBJECTIVE:

To evaluate nuclear factor kappaB (NF-κB) activation and NF-κB-p65 subunit activation, immunolocalization, and expression in the endometrium of healthy women and endometriosis patients throughout the menstrual cycle.

DESIGN:

Prospective observational study.

SETTING:

Affiliated hospital and university research laboratory.

PATIENT(S):

Twenty-four healthy women and 24 endometriosis patients.

INTERVENTION(S):

Menstrual, proliferative, and secretory endometrial biopsies.

MAIN OUTCOME MEASURE(S):

Assessment of NF-κB and p65 activation by protein-DNA binding assays and p65 localization and expression by immunohistochemistry.

RESULT(S):

Total NF-κB-DNA binding was constitutive and variable in human endometrium accross the menstrual cycle. Healthy women (physiologic conditions) showed higher p65-DNA binding in proliferative than in menstrual and secretory endometrium. Conversely, in endometriosis patients, p65-DNA binding was higher in proliferative and secretory endometrium than in menstrual endometrium. Endometrial epithelial cells showed higher p65 expression level score than endometrial stromal cells.

CONCLUSION(S):

NF-κB activity is constitutive, physiologic, and variable in human endometrium. The physiologic cyclic p65 activation pattern was altered in endometriosis patients, showing no cyclic variation between the proliferative and secretory phase of the menstrual cycle. The absence of decreased p65 activity in secretory endometrium from endometriosis patients is concurrent with progesterone resistance and could participate in endometrial biologic alterations during the implantation window in endometriosis patients.

Fertil Steril.2012 Mar;97(3):657-64. Epub 2011 Dec 21.

Peroxisome proliferating activating receptor gamma-independent attenuation of interleukin 6 and interleukin 8 secretion from primary endometrial stromal cells by thiazolidinediones.

McKinnon B, Bersinger NA, Mueller MD.

Source

Department of Obstetrics and Gynecology, Inselspital, Berne University Hospital, University of Berne, Berne, Switzerland. brett.mckinnon@dkf.unibe.ch

Abstract

OBJECTIVE:

To assess the effect of thiazolidinediones on the regulation of inflammatory cytokines related to endometriosis in endometrial tissue and determine whether these effects occur via activation of the peroxisome proliferating activating receptor gamma (PPAR)-γ.

DESIGN:

In vitro study using eutopic endometrial tissue.

SETTING:

University hospital.

PATIENT(S):

Premenopausal women undergoing laparoscopy for infertility or abdominal pain.

INTERVENTION(S):

Isolation of endometrial stromal cells and the culture of these cells in the presence of thiazolidinediones, ciglitazone and pioglitazone, both with and without a pretreatment of the specific, irreversible PPAR-γ antagonist GW9662.

MAIN OUTCOME MEASURE(S):

Quantitation of interleukin (IL)-6 and IL-8 released into the cell culture medium by ELISA. Real-time polymerase chain reaction to quantitate PPAR-γ gene expression in the primary cell preparations and the expression of IL-6 and IL-8 after thiazolidinedione treatment.

RESULT(S):

Treatment of stromal cells with thiazolidinediones attenuated IL-6 and IL-8 release in a dose-dependent manner. This effect was not inhibited by GW9662 pretreatment. Ciglitazone induced IL-6 messenger RNA expression, an effect that was suppressed by GW9662 pretreatment.

CONCLUSION(S):

Thiazolidinediones decrease the proinflammatory cytokines IL-6 and IL-8 in endometrial stromal cells via a PPAR-γ-independent mechanism. A better understanding of the anti-inflammatory action of this class of drugs may improve their safety and efficacy for endometriosis treatment.

Ginekol Pol.2012 Mar;83(3):209-13.

Conservative treatment of endometriosis.

[Article in Polish]

Drews K, Barlik M, Łukaszewski T.

Source

Klinika Perinatologii i Chorób Kobiecych,Uniwersytet Medyczny w Poznaniu, Polska.

Abstract

Endometriosis is a common disease concerning 5-10% of women at reproductive age. It may cause sterility and decrease the quality of life. The best known symptoms are dysmenorrhea, dyspareunia, chronic pelvic pain and pain related to ovulation. Endometriosis is a chronic illness which, so far can not be completely cured. Clinical treatment is focused on decreasing symptoms, improving the quality of life, inhibition of endometrial focuses, sustaining sterility and preventing recurrences. Most of the time clinical treatment is not limited only to one possibility but usually joins a few therapeutic options. One of the possibilities is the surgical treatment, usually laparoscopic. Conservative treatment may be its completion. The main medical aim of conservative treatment is to decrease pain by inhibition of inflammation and to reduce or arrest the production of cyclic ovarian hormones, what usually leads to amenorrhea. Drugs used in conservative treatment of endometriosis are often connected with numerous side effects, constituting a serious limitation of a long-term therapy. That is the reason why much research concentrates on finding the optimal medical procedures for patients with endometriosis.

Gut.2012 Mar;61(3):367-72. Epub 2011 Aug 25.

Visceral hypersensitivity in endometriosis: a new target for treatment?

Issa B, Onon TS, Agrawal A, Shekhar C, Morris J, Hamdy S, Whorwell PJ.

Source

Department of Translational Medicine, University of Manchester, Manchester, UK.

Abstract

OBJECTIVE:

In women presenting to gynaecological clinics with lower abdominal pain, the cause is frequently attributed to endometriosis irrespective of whether it is found to be minimal or extensive at laparoscopy. Irritable bowel syndrome (IBS) is also common in this setting, and it was speculated that the visceral hypersensitivity associated with this condition might be amplifying the symptoms of endometriosis.

METHODS:

Visceral sensitivity to balloon distension, symptoms and psychological status were assessed following laparoscopy in 20 women with minimal to mild endometriosis, 20 with moderate to severe endometriosis, 20 with laparoscopy negative abdominal pain and 20 asymptomatic women undergoing laparoscopic sterilisation who acted as controls, and compared with 20 women with IBS.

RESULTS:

Compared with controls, patients with minimal to mild and moderate to severe endometriosis had a higher prevalence of symptoms consistent with IBS (0% vs 65% and 50%, respectively, p<0.001) with significantly lower mean pain thresholds (39.5 mm Hg (95% CI 36.0 to 43.0) vs 28.1 mm Hg (95% CI 24.5 to 31.6), p=0.001 and 28.8 mm Hg (95% CI 24.9 to 32.6), p=0.002) not explained by differences in rectal compliance. Patients with laparoscopy negative pain had symptoms and visceral sensitivity similar to patients with IBS. Controls undergoing laparoscopy had normal sensitivity, indicating that the laparoscopic procedure was not inducing hypersensitivity.

CONCLUSION:

Visceral hypersensitivity is extremely common in endometriosis and could be intensifying the pain. This finding might explain why mildly affected individuals often complain of severe symptoms out of proportion to the extent of their disease. This study has introduced a completely new concept into the understanding of pain in endometriosis and could open up new opportunities for treatment.

Gynecol Endocrinol.2012 Mar;28(3):220-3. Epub 2011 Dec 1.

Chitotriosidase levels in patients with severe endometriosis.

Alanbay İ, Coksuer H, Ercan CM, Sakinci M, Karaşahin E, Ceyhan ST, Ustun Y, Kurt I, Ozbilen N, Baser I.

Source

Gulhane Military Medical Faculty, Obstetrics and Gynecology Department, 06018, Etlik, Ankara, Turkey. ialanbay@gmail.com

Abstract

OBJECTIVE:

To study the levels of chitotriosidase activity in the peritoneal fluid and the plasma of patients with severe endometriosis and control subjects.

MATERIALS AND METHODS:

Twenty-five women with laparoscopically and histopathologically confirmed endometriosis (study group) and 27 control patients who had undergone laparoscopic surgery were included. Peritoneal fluid and peripheral blood were obtained from all the patients before the surgery. Chitotriosidase activities were measured.

RESULTS:

Analysis of chitotriosidase activity in the peritoneal fluid of patients with endometriosis showed that there was no significant difference between endometriosis and control group, respectively (32.04 ± 64.20 vs. 15.25 ± 31.17 nmol/mL/h; p > 0.05). Analysis of chitotriosidase activity in plasma of patients with endometriosis showed significantly increased levels of chitotriosidase levels compared with the control group (74.81 ± 60.54 vs. 14.10 ± 26.17; p < 0.001), respectively.

CONCLUSION:

We found that the activity of chitotriosidase in plasma was statistically higher in severe endometriosis patients than women without endometriosis.