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Int J Med Robot.2012 Jun;8(2):160-5. doi: 10.1002/rcs.451. Epub 2011 Dec 9.

Robotics as a new surgical minimally invasive approach to treatment of endometriosis: a systematic review.

Carvalho L, Abrão MS, Deshpande A, Falcone T.


Center for Reproductive Medicine, Obstetrics and Gynecology and Women’s Health Institute, Cleveland Clinic, Cleveland, Ohio, 44195, USA.



This systematic review evaluates the role of robotics in the surgical treatment of endometriosis.


Electronic database searches were conducted in MEDLINE, Scopus, and ISI Web of Knowledge for relevant studies over the past 10 years.


Four published articles were found that used robotic assisted laparoscopy to perform endometriosis surgery. All four studies used the da Vinci Surgical System (Intuitive Surgical Inc., Sunnyvale, CA, USA). Three studies were case reports, and one was a cohort study. Robotics appears to be as effective as conventional laparoscopy in the management of endometriosis. There were no reports of any major complications.


Few studies have been published and show us that robotic endometriosis surgery is feasible even in severe endometriosis cases without conversion. There is a lack of long-term outcome papers in the literature. Randomized controlled trials are necessary.

Int J Oncol.2012 Jun;40(6):1755-62. doi: 10.3892/ijo.2012.1384. Epub 2012 Feb 21.

Progestin therapy for endometrial cancer: the potential of fourth-generation progestin (review).

Banno K, Kisu I, Yanokura M, Tsuji K, Masuda K, Ueki A, Kobayashi Y, Yamagami W, Nomura H, Susumu N, Aoki D.


Department of Obstetrics and Gynecology, School of Medicine, Keio University, Tokyo, Japan. kbanno@sc.itc.keio.ac.jp


Progestin preparations are made of synthetic progesterone and have often been used for hormone therapy in gynecological patients with endometriosis or endometrial cancer. Hormone therapy using progestin is considered to be one of the effective means of treatment particularly when dealing with endometrial cancer (an estrogen-dependent tumor). Numerous reports have been published concerning its efficacy in advanced or recurrent cases of atypical endometrial hyperplasia or endometrial cancer. Dienogest has been developed as a fourth-generation progestin for hormone therapy for endometriosis that can be used with high safety for long periods of time. In Japan, dienogest has been recommended as a first-line drug for endometriosis-associated pain. However, its antitumor activity has also been attracting close attention following a report that this drug suppressed the proliferation in vitro of endometrial cancer-derived cell lines which failed to respond to other progestins such as medroxyprogesterine acetate (MPA). The mechanism for antitumor activity of dienogest is considered to differ from the mechanism for antitumor activity of conventional progestin preparations used for treatment of endometrial cancer. This drug is expected to be clinically applicable as a new drug for the treatment of endometrial cancer.

Int J Surg Pathol.2012 Jun;20(3):301-4. Epub 2011 Oct 13.

Abdominal wall endometriosis associated with ventriculoperitoneal and lumboperitoneal shunts: a report of 2 cases of an extremely rare phenomenon.

Healy EG, McCluggage WG.


1Belfast Health and Social Care Trust, Belfast, Northern Ireland.


Endometriosis is a common condition in women of reproductive age and has a known propensity to involve abdominal wall scars. The authors report 2 cases of endometriosis presenting as mass lesions involving the abdominal wall at the site of insertion of ventriculoperitoneal and lumboperitoneal shunts. In both cases, there was clinical evidence of shunt compromise. Endometriosis involving the site of shunt insertion is an extremely rare phenomenon with, as far as the authors are aware, only a single previously reported case. However, it should be considered in the differential diagnosis when a mass develops at a shunt site in a woman of reproductive age.

J Exp Clin Cancer Res.2012 Jun 1;31(1):53. [Epub ahead of print]

Clear cell carcinoma of the ovary: Is there a role of histology-specific treatment?

Takano M, Tsuda H, Sugiyama T.


ABSTRACT: Several clinical trials to establish standard treatment modality for ovarian cancers included a high abundance of patients with serous histologic tumors, which were quite sensitive to platinum-based chemotherapy. On the other hand, ovarian tumor with rare histologic subtypes such as clear cell or mucinous tumors have been recognized to show chemo-resistant phenotype, leading to poorer prognosis. Especially, clear cell carcinoma of the ovary (CCC) is a distinctive tumor, deriving from endometriosis or clear cell adenofibroma, and response rate to platinum-based therapy is extremely low. It was implied that complete surgical staging enabled us to distinguish a high risk group of recurrence in CCC patients whose disease was confined to the ovary (pT1M0); however, complete surgical staging procedures could not lead to improved survival. Moreover, the status of peritoneal cytology was recognized as an independent prognostic factor in early-staged CCC patients, even after complete surgical staging. In advanced cases with CCC, the patients with no residual tumor had significantly better survival than those with the tumor less than 1 cm or those with tumor diameter more than 1 cm. Therefore, the importance of achieving no macroscopic residual disease at primary surgery is so important compared with other histologic subtypes. On the other hand, many studies have shown that conventional platinum-based chemotherapy regimens yielded a poorer prognosis in patients with CCC than in patients with serous subtypes. The response rate by paclitaxel plus carboplatin (TC) was slightly higher, ranging from 22% to 56%, which was not satisfactory enough. Another regimen for CCC tumors is now being explored: irinotecan plus cisplatin, and molecular targeting agents. In this review article, we discuss the surgical issues for early-staged and advanced CCC including possibility of fertility-sparing surgery, and the chemotherapy for CCC disease.

J Obstet Gynaecol Can.2012 Jun;34(6):552-7.

Clinical predictors of endometriosis in the infertility population: is there a better way to determine who needs a laparoscopy?

Whitehill K, Yong PJ, Williams C.


Department of Obstetrics and Gynaecology, University of British Columbia, Vancouver BC.


Objective: Endometriosis is a known contributor to infertility, but the gold standard for its diagnosis is surgical. Therefore, it is important for clinicians to be able to predict which women with infertility are at high risk for endometriosis and thus should be offered laparoscopy. We sought to identify the clinical predictors of endometriosis in the infertility population. Methods: We conducted a retrospective review of patients at an academic infertility centre. The primary outcome was identification of endometriosis at laparoscopy, and we used logistic regression to test clinical variables for their ability to predict endometriosis. Results: Primary infertility, dysmenorrhea, and uterosacral/cul-de-sac nodularity were significant independent predictors of finding endometriosis at laparoscopy. Other clinical variables (including hysterosalpingogram findings) were not independent predictors of endometriosis, and physicians with an endometriosis-focused practice were more likely to diagnose endometriosis at laparoscopy. Conclusion: Key predictors of endometriosis in the infertility population are primary infertility, dysmenorrhea, and uterosacral/cul-de-sac nodularity. These results will be used to develop and validate a formal clinical prediction model for endometriosis in infertile women.

J Vet Sci.2012 Jun;13(2):171-7.

The role of inflammation and matrix metalloproteinases in equine endometriosis.

Aresu L, Benali S, Giannuzzi D, Mantovani R, Castagnaro M, Falomo ME.


Dipartimento di Sanità Pubblica, Patologia Comparata e Igiene Veterinaria, Facoltà di Medicina Veterinaria, Viale dell’Università, 16-35020-Legnaro (Padova) 049-8272963, Italy. luca.aresu@unipd.it.


Equine endometriosis is a multifactorial disease considered to be a major cause of equine infertility. The purpose of this study was to evaluate the reliability of histomorphological grading for biopsy-like samples compared to entire uterine wall samples, to examine the association between the degree of endometriosis with animal age, and to investigate the role of inflammation in endometriosis and the expression of different matrix metalloproteinases in equine endometrium. Histomorphological lesions in 35 uterine samples were examined while comparing biopsy-like samples and entire-wall samples. Seventeen uterine samples were stained with antibodies against MMP-2, MMP-9, MMP-14, and TIMP-2. The morphologic evaluation results of the biopsy-like tissue and entire-wall samples were significantly correlated. Endometriosis in older mares (>12 years of age) was more severe than in young mares (2 ˜ 4 years of age), confirming the positive correlation between animal age and disease severity, while inflammation was poorly related to the degree of endometriosis. MMP-2 and MMP-14 were detected in stromal cells, while MMP-9 and TIMP-2 were both found in stromal and glandular epithelial cells. There were no significant differences in MMPs expression between the two groups (young vs. old mares). Additional studies on the activity of MMPs could further define the role of these enzymes in equine endometriosis.

Med Sci Monit.2012 Jun 1;18(6):CR361-367.

Increased expression of importin13 in endometriosis and endometrial carcinoma.

Zeng B, Hu J, Yuan R, Hu L, Zhong L, Kang K.


Department of Obstetrics and Gynecology, Second Affiliated Hospital, Chongqing Medical University, Chongqing, China.


Background: Importin13 (IPO13) is a novel potential marker of corneal epithelial progenitor cells. We investigated the expression and localization of IPO13 in endometrial, endometriotic and endometrial carcinoma tissue.<br /> Material/Methods: IPO13 expression in endometrial, endometriotic and endometrial carcinoma tissue was examined by immunohistochemistry, qPCR and Western blot.<br /> Results: Immunohistochemistry studies showed that IPO13 protein was expressed mainly in cytoplasm of glandular epithelial cell and stromal cells. The rate of importin13-positive cells in proliferative phase endometrium was higher (by about 6-fold) than that in secretory endometrium (P<0.05) and the rate of importin13-positive cells in endometriosis and endometrial carcinoma was higher than that in normal secretory phase endometrial tissues (by about 4- and 9-fold, respectively). Immunofluorescence microscopy revealed co-localization of IPO13 with CD34, CD45, c-kit, telomerase, CD90 and CD146. QPCR revealed significantly increased IPO13 mRNA in endometriosis and endometrial carcinoma versus secretory phase endometrium (by about 2- and 10-fold, respectively). Western blot analysis showed that IPO13 protein is enhanced in endometriosis and endometrial carcinoma versus secretory phase endometrium (p<0.05).<br /> Conclusions: These results demonstrate an increased expression of IPO13 in endometriosis and endometrial carcinoma, which could be involved in the pathogenesis of endometriosis and endometrial carcinoma; IPO13 can serve as an endometrial progenitor/stem cell marker.<br />

Menopause Int.2012 Jun;18(2):73-6.

Potential strategies to avoid progestogen-induced premenstrual disorders.

Baker LJ, O’Brien PM.


Obstetrics & Gynaecology, Keele University, School of Medicine, Newcastle Road, Stoke-On-Trent ST4 6QG, UK. Shaughn.O’Brien@uhns.nhs.uk.


Non-hormonal approaches to premenstrual syndrome (PMS) treatment such as selective serotonin reuptake inhibitors are by no means effective for all women and frequently we must resort to endocrine therapy. During many of the hormonal approaches, PMS-like symptoms can be introduced or re-introduced during the necessary cyclical or continuous progestogen component of the therapy. This is seen with combined oral contraception, progestogen only contraception, progestogen therapy for heavy menstrual bleeding and endometriosis, sequential hormone replacement therapy and any therapeutic strategy for premenstrual syndrome where it is necessary to provide endometrial protection, including estrogen suppression of ovulation or add-back during gonadotrophin releasing hormone suppression. The link to progestogen is very often missed by health professionals. When the pattern of symptoms mimics the cyclicity of PMS, it is termed progestogen-induced premenstrual disorder. The need to use progestogen to protect the endometrium from the proliferative actions of estrogen can pose insurmountable difficulties in managing premenstrual disorders. In the absence of any really useful evidence, nearly all practice in this area depends on clinician experience. We cannot afford to wait for adequate research evidence to be produced – it never will – and so we must rely on empirical findings, clinical experience, theoretical strategies and common sense.

Menopause Int.2012 Jun;18(2):68-72.

Gonadotrophin receptor hormone analogues in combination with add-back therapy: an update.

McLaren JS, Morris E, Rymer J.


Correspondence: James Samuel McLaren. Email: jsmclaren@doctors.org.uk.


Gonadotrophin receptor hormone analogues (GnRHa) have been used in a range of sex hormone-dependent disorders. In the management of premenstrual syndrome, they can completely abolish symptoms. The success of GnRHa in the treatment of endometriosis and adjuvant therapy in the management of fibroids is proven. This efficacy does not come without a cost and the side-effects of the hypo-estrogenic state have limited their application. The use of add-back therapy to counter these effects has enabled wider application, longer durations of treatment and an increase in compliance. This review article is an update on the evidence supporting gonadotrophin receptor hormone analogues in combination with add-back therapy.

Minerva Ginecol.2012 Jun;64(3):231-8.

The role of EHP-30 as specific instrument to assess the quality of life of Italian women with endometriosis.

Maiorana A, Scafidi Fonti GM, Audino P, Rosini R, Alio L, Oliveri AM, Milito AM.


Department of Obstetrics and Gynecology, ARNAS Civico Hospital, Palermo, Italy – maioran@alice.it.



Our goals were to assess the psychometrical characteristics of EHP-30, to test its higher degree of appropriateness compared to the generic Quality of Life-assessment tools for Italian women suffering from endometriosis, and to determine its ability to identify the disease’s effects on the patients’ psychosocial condition, highlighting critical points that can be modified for future linguistic validation.


Participants to our study were 98 women between 19 and 51-year-old (M=34.4, SD=7.5), selected from patients of the Department of Obstetrics and Gynecology, ARNAS Civico Hospital, Palermo, Italy. All of them had a surgical diagnosis of endometriosis with histological confirmation. Quality of Life was assessed through generic (SF-36) and specific (EHP-30) instruments.


Our study shows that the current Italian version of EHP-30 is affected by overall weaker construct validity than the English one; it seems that this has to be ascribed to the inadequacy of the EHP-30 translation into Italian. In particular, unsatisfactory reliability levels have been observed for social support and self-image scales. An incorrect order of response categories has been in addition found out for several items of the Italian version of EHP-30. Research results suggest solutions to adopt for a revision of the EHP-30 Italian version that can satisfy the requirements of validity and reliability.


Although requiring a structural and linguistic revision, also the Italian version of a specific measurement instrument as EHP-30 is, appears to be more appropriate than generic tools to assess the quality of life of Italian women suffering for endometriosis.

Mod Pathol.2012 Jun;25(6):885-92. doi: 10.1038/modpathol.2011.217. Epub 2012 Feb 3.

Loss of ARID1A/BAF250a-expression in endometriosis: a biomarker for risk of carcinogenic transformation?

Samartzis EP, Samartzis N, Noske A, Fedier A, Caduff R, Dedes KJ, Fink D, Imesch P.


Department of Gynecology, University Hospital Zurich, Zurich, Switzerland.


Mutations of the tumor-suppressor gene ARID1A result in the loss of protein expression of the BRG-associated factor 250a (BAF250a), a large subunit of transcription-regulating Human SWI/SNF complexes, which have an important role in the control of cell proliferation and tumor suppression. ARID1A mutations are particularly frequent in endometriosis-associated ovarian clear cell and endometrioid carcinomas, and were recently described as a possible key mechanism and early step in the transformation of endometriosis into cancer. Here, we examined the immunohistochemical expression pattern of BAF250a in a tissue microarray including 74 endometriosis and 30 endometrium samples. Ovarian cancer samples (n=136) served as a control. Epithelial BAF250a expression was assessable in 90/104 (87%) and stromal BAF250a expression in 95/104 (91%) of the endometriosis, and endometrium cases due to lack of adequate tissue in some spots. Complete lack of BAF250a expression was observed in three endometriomas (n=3/20, 15%) and one deep-infiltrating endometriosis sample (n=1/22, 5%), but in none of the peritoneal endometriosis (n=0/16) and eutopic endometrium samples (n=0/30). A comparison of the mean immunoreactivity scores revealed a significantly lower expression rate of BAF250a in endometriomas compared with normal endometrium (P<0.0005), as well as peritoneal (P=0.003) and deep-infiltrating endometriosis (P=0.02). Our data demonstrates that a complete loss of BAF250a expression is observable in some endometriotic lesions, especially in endometriomas. In addition, we report that a partial loss of BAF250a expression is occurring in the form of cell clusters indicating a clonal loss of BAF250a expression in these cells. The loss of expression of the tumor-suppressor protein BAF250a in some endometriomas possibly indicates a risk of malignant transformation in these cases, which could be of importance in the determination of individual treatment strategies. However, its role and value as a prognostic parameter in endometriosis needs to be further studied.

Mol Hum Reprod.2012 Jun;18(6):308-19. Epub 2012 Feb 3.

Alterations in progesterone receptor membrane component 2 (PGRMC2) in the endometrium of macaques afflicted with advanced endometriosis.

Keator CS, Mah K, Slayden OD.


Division of Reproductive Sciences, Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, OR, USA.


The hormonally driven expression and cell-specific localization patterns of the progesterone receptor membrane components (PGRMC1 and PGRMC2) in the macaque endometrium during the menstrual cycle are unknown. Additionally, the expression and localization patterns of PGRMC1 and PGRMC2 in the secretory eutopic endometrium of primates afflicted with endometriosis are also unknown. Therefore, we used real-time PCR to quantify transcript expression levels of the PGRMCs in well-defined samples of endometrium collected from artificially cycled macaques during the menstrual cycle, and in the secretory phase endometrium of naturally cycling macaques afflicted with endometriosis. In situ hybridization and immunocytochemistry were used to localize PGRMC1 and PGRMC2 mRNA and protein, respectively. We compared the patterns of expression and localization of the PGRMCs with the expression and localization patterns of nuclear progesterone receptor (PGR). PGRMC1 and PGR were elevated during the proliferative phases of the cycle, and then declined to nearly undetectable levels during the late secretory phase of the cycle. Levels of PGRMC2 were lowest during the proliferative phases of the cycle and then increased markedly during the secretory phases. Strong staining for PGRMC2 was localized to the luminal and glandular epithelia during the secretory phases. When compared with artificially cycled disease-free animals, macaques with endometriosis exhibited no changes in the expression or localization patterns for PGR and PGRMC1 but exhibited strikingly reduced levels of PGRMC2 transcript and altered intracellular staining patterns for the PGRMC2 protein. Collectively, these results suggest that membrane-bound PGRMC2 may provide a pathway of action that could potentially mediate the non-genomic effects of progesterone on the glandular epithelia during the secretory phase of the cycle. Further, reduced levels of membrane-bound PGRMC2 may be associated with the progesterone insensitivity often observed in the endometrium of primates afflicted with endometriosis.

Obstet Gynecol Surv.2012 Jun;67(6):374-81.

Serum and peritoneal fluid immunological markers in adolescent girls with chronic pelvic pain.

Drosdzol-Cop A, Skrzypulec-Plinta V, Stojko R.


*Physician, Clinical Assistant, †Professor, Woman’s Health Institute, The Medical University of Silesia, Katowice, Poland.


The aim of this study was to determine serum and peritoneal interleukin (IL)-2, IL-4, and monocyte chemotactic protein-1 levels as diagnostic markers of endometriosis in adolescent girls. The design of the study encompassed 50 adolescent girls, aged 13 to 19 years after menarche, with chronic pelvic pain who qualified for diagnostic laparoscopy. The patients were allocated into 2 groups: group I (endometriosis) consisted of subjects with diagnosed endometriosis (n = 33, 66%) and group II (control) whose laparoscopic examinations revealed no evidence of endometriosis (n = 17, 34%). IL-2, IL-4, and Monocyte chemotactic protein 1 concentrations in serum and peritoneal samples were assessed using commercially available human enzyme-linked immunosorbent assay kits. The results were analyzed statistically with the Statistica 8.0 computer software. The value of P < 0.05 was the level of statistical significance. The results in adolescents with endometriosis had significantly higher concentrations of serum IL-4 (3.90 ± 1.58 pg/mL vs. 3.04 ± 1.72 pg/mL; P = 0.04) and peritoneal fluid IL-4 (5.03 ± 8.92 pg/mL vs. 2.74 ± 1.11 pg/mL; P = 0.03), and lower peritoneal fluid IL-2 (92.44 ± 292.75 pg/mL vs. 174.23 ± 389.77 pg/mL; P = 0.01) compared with the control. In a receiver-operating characteristic analysis, serum IL-4 as well as peritoneal fluid IL-2 and IL-4 provided the best discriminative ability between subjects with endometriosis and controls. Using cutoff points for serum IL-4 (3.00 pg/mL), peritoneal fluid IL-2 (21.00 pg/mL) and IL-4 (2.7 pg/mL), relatively high odd ratios were obtained in the prediction of endometriosis in adolescents (3.2; 6.4; 3.3). The Serum IL-4, peritoneal IL-2 and IL-4 provided a good method of discrimination between subjects with endometriosis and controls. Target Audience: Obstetricians & Gynecologists, Family Physicians Learning Objectives: After completion of this educational activity, the reader will be able to Analyze the prevalence and clinical presentation of endometriosis in adolescents, which is significantly different from typical symptomatology observed in adult women. Assess the role of serum and peritoneal fluid IL-2, IL-4, and MCP-1 levels as diagnostic markers of endometriosis in adolescent girls. Use the cutoff value of serum IL-4 as well as peritoneal fluid IL-2 and IL-4 levels as the discrimination method between subjects with endometriosis and controls.

Pain Med.2012 Jun;13(6):777-89. doi: 10.1111/j.1526-4637.2012.01385.x. Epub 2012 May 8.

Evoked pain analgesia in chronic pelvic pain patients using respiratory-gated auricular vagal afferent nerve stimulation.

Napadow V, Edwards RR, Cahalan CM, Mensing G, Greenbaum S, Valovska A, Li A, Kim J, Maeda Y, Park K, Wasan AD.


Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Charlestown, MassachusettsDepartments of Anesthesiology Psychiatry, Brigham and Women’s Hospital, Boston, Massachusetts, USA Department of Biomedical Engineering, Kyunghee University, Yongin, Republic of Korea.


Objective. Previous vagus nerve stimulation (VNS) studies have demonstrated antinociceptive effects, and recent noninvasive approaches, termed transcutaneous-vagus nerve stimulation (t-VNS), have utilized stimulation of the auricular branch of the vagus nerve in the ear. The dorsal medullary vagal system operates in tune with respiration, and we propose that supplying vagal afferent stimulation gated to the exhalation phase of respiration can optimize t-VNS. Design. Counterbalanced, crossover study. Patients. Patients with chronic pelvic pain (CPP) due to endometriosis in a specialty pain clinic. Interventions/Outcomes. We evaluated evoked pain analgesia for respiratory-gated auricular vagal afferent nerve stimulation (RAVANS) compared with nonvagal auricular stimulation (NVAS). RAVANS and NVAS were evaluated in separate sessions spaced at least 1 week apart. Outcome measures included deep-tissue pain intensity, temporal summation of pain, and anxiety ratings, which were assessed at baseline, during active stimulation, immediately following stimulation, and 15 minutes after stimulus cessation. Results. RAVANS demonstrated a trend for reduced evoked pain intensity and temporal summation of mechanical pain, and significantly reduced anxiety in N=15 CPP patients, compared with NVAS, with moderate to large effect sizes (η(2) >0.2). Conclusion. Chronic pain disorders such as CPP are in great need of effective, nonpharmacological options for treatment. RAVANS produced promising antinociceptive effects for quantitative sensory testing (QST) outcomes reflective of the noted hyperalgesia and central sensitization in this patient population. Future studies should evaluate longer-term application of RAVANS to examine its effects on both QST outcomes and clinical pain.

Wiley Periodicals, Inc.

Reprod Sci.2012 Jun;19(6):563-71. Epub 2012 Mar 27.

The hormonal profile of norethindrone acetate: rationale for add-back therapy with gonadotropin-releasing hormone agonists in women with endometriosis.

Chwalisz K, Surrey E, Stanczyk FZ.


1Abbott Laboratories, Abbott Park, IL, USA.


Gonadotropin-releasing hormone agonists (GnRHa) are an effective treatment of endometriosis-associated pelvic pain. The use of hormonal add-back therapy can alleviate the hypoestrogenic symptoms associated with GnRHa therapy, while preserving therapeutic efficacy. Norethindrone acetate (NETA) is a unique progestin that has both estrogenic and androgenic properties and is effective as an add-back regimen without estrogen supplementation. Through its estrogenic activity, NETA exerts beneficial effects on bone mineral density and vasomotor symptoms in women treated with GnRHa. In addition, NETA exhibits strong endometrial antiproliferative effects, which may result in further benefits for the endometriosis patient population. However, NETA add-back may be associated with progestogenic side effects and may lower high-density lipoprotein due to androgenic activity. These effects must be balanced with the overall benefits of NETA add-back therapy.

Reprod Sci.2012 Jun;19(6):572-9. Epub 2012 Jan 19.

Statins inhibit monocyte chemotactic protein 1 expression in endometriosis.

Cakmak H, Basar M, Seval-Celik Y, Osteen KG, Duleba AJ, Taylor HS, Lockwood CJ, Arici A.


1Department of Obstetrics, Gynecology & Reproductive Sciences, Yale University School of Medicine, New Haven, CT, USA.


Statins are potent inhibitors of the endogenous mevalonate pathway. Besides inhibiting cholesterol biosynthesis, statins may also demonstrate anti-inflammatory properties. Inflammation is implicated in the attachment and invasion of endometrial cells to the peritoneal surface and growth of ectopic endometrium by inducing proliferation and angiogenesis. In this study, the effect of statins on monocyte chemotactic protein 1 (MCP-1) expression in endometriotic implants in nude mouse model and in cultured endometriotic cells was evaluated. In mouse model, simvastatin decreased MCP-1 expression in a dose-dependent manner in endometriotic implants (P < .05). Similarly, both simvastatin and mevastatin revealed a dose-dependent inhibition of MCP-1 production in cultured endometriotic cells (P < .01). This inhibitory effect of the statins on MCP-1 production was reversed by the downstream substrates of the mevalonate pathway. Moreover, statins decreased MCP-1 messenger RNA expression in cultured endometriotic cells (P < .05). In conclusion, statins exert anti-inflammatory effect in endometriotic cells and could provide a potential treatment of endometriosis in the future.

Sex Reprod Healthc.2012 Jun;3(2):93-4. Epub 2012 Feb 17.

Pertubation with lidocaine–a non-hormonal, long-term treatment of dysmenorrhea due to endometriosis.

Edelstam G, Sjösten A, Jablonowska B, Kjellberg S, Spira J.


Department of Obstetrics and Gynaecology, SE 751 85 Uppsala, Sweden. Greta.Edelstam@akademiska.se


The major symptoms of endometriosis are dysmenorrhea and infertility. Pertubations with lidocaine have been shown to reduce dysmenorrhea and have an enhancing effect on fertility. Different concentrations of lidocaine were evaluated in a randomized, double-blind study of pre-ovulatory pertubations with lidocaine solutions in women with dysmenorrhea. The patients had laparoscopically diagnosed endometriosis and normal fallopian tubes. Ninety pertubations were carried out without complications on 26 patients during up to six cycles. The effect was evaluated by means of questionnaires where a clinically significant reduction of dysmenorrhea was reported. Pertubation with lidocaine can be a non-hormonal treatment option for dysmenorrhea.

Steroids.2012 Jun;77(7):765-73. Epub 2012 Apr 5.

Biological characterization of non-steroidal progestins from botanicals used for women’s health.

Toh MF, Sohn J, Chen SN, Yao P, Bolton JL, Burdette JE.


Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago, Chicago, IL 60607, USA.


Progesterone plays a central role in women’s reproductive health. Synthetic progestins, such as medroxyprogesterone acetate (MPA) are often used in hormone replacement therapy (HRT), oral contraceptives, and for the treatment of endometriosis and infertility. Although MPA is clinically effective, it also promiscuously binds to androgen and glucocorticoid receptors (AR/GR) leading to many undesirable side effects including cardiovascular diseases and breast cancers. Therefore, identifying alternative progestins is clinically significant. The purpose of this study was to biologically characterize non-steroidal progestins from botanicals by investigating theirinteraction and activation of progesterone receptor (PR). Eight botanicals commonly used to alleviate menopausal symptoms were investigated to determine if they contain progestins using a progesterone responsive element (PRE) luciferase reporter assay and a PR polarization competitive binding assay. Red clover extract stimulated PRE-luciferase and bound to PR. A library of purified compounds previously isolated from red clover was screened using the luciferase reporter assay. Kaempferol identified in red clover and a structurally similar flavonoid, apigenin, bound to PR and induced progestegenic activity and P4 regulated genes in breast epithelial cells and human endometrial stromal cells (HESC). Kaempferol and apigenin demonstrated higher progestegenic potency in the HESC compared to breast epithelial cells. Furthermore, phytoprogestins were able to activate P4 signaling in breast epithelial cells without downregulating PR expression. These data suggest that botanical extracts used for women’s health may contain compounds capable of activating progesterone receptor signaling.

Syst Biol Reprod Med.2012 Jun;58(3):149-53. Epub 2012 Apr 20.

The influence of the redox state of follicular fluid albumin on the viability of aspirated human oocytes.

Otsuki J, Nagai Y, Matsuyama Y, Terada T, Era S.


Nagai Clinic, Kamihikona Misato, Saitama, Japan. otsuki.midori.junko@gmail.com


A number of reports have suggested that the oxidative state of human albumin in serum and in some body fluids is associated with cell damage. However there are no reports on the redox state of human follicular fluid (FF) and its influence on oocyte viability. The aim of this study was to examine the relationship between the redox state of FF and serum on oocyte viability. The cytoplasmic condition of oocytes was evaluated microscopically at collection in 117 women. Deteriorating oocytes were recognized by degenerative changes in their cytoplasm. The redox state of FFs that yielded degenerated oocytes was evaluated and compared with fluids containing normal oocytes. The redox state of the corresponding FF and serum, at the time of oocyte retrieval, was analyzed by high performance liquid chromatography. The redox state of FF that contained degenerated oocytes was found to have a significantly elevated oxidized state compared with the FFs that yielded normal oocytes. Also the albumin in the FF of patients was found to be predominantly in the reduced state compared with that in their serum at the time of oocyte retrieval. In addition, increasing age and endometriosis were found to shift the redox of serum to the oxidative state. We propose that the reduced state of albumin in FF may play an important role in protecting oocytes from oxidative damage.

Urology.2012 Jun;79(6):e84-5.

Clear cell adenocarcinoma arising from abdominal wall endometriosis mimicking urachal tumor.

Sawazaki H, Goto H, Takao N, Taki Y, Takeuchi H.


Department of Urology, Toyooka Hospital, Toyooka, Hyogo, Japan.


A 41-year-old woman presented with severe lower abdominal pain. She had a history of 2 cesarean deliveries. Magnetic resonance imaging (MRI) revealed a 4.3 × 4.6 × 4.8-cm mass on the urinary bladder dome. Preoperative diagnosis was invasive urachal tumor. Wide resection of the tumor was performed. The histopathological diagnosis was clear cell adenocarcinoma with endometriosis. MRI revealed normal-sized ovaries and uterus. The definite diagnosis of clear cell carcinoma arising from abdominal wall endometriosis was made. Adjuvant chemotherapy with paclitaxel and carboplatin (total 6 courses) was planned. The patient has thus far received 4 courses of this treatment.

Arch Gynecol Obstet.2012 May 31. [Epub ahead of print]

Therapeutic efficiency of Atosiban, an oxytocin receptor blocking agent in the treatment of experimental endometriosis.

Simsek Y, Celik O, Karaer A, Gul M, Yılmaz E, Koc O, Colak C, Zengin S, Aydin NE.


Department of Obstetrics and Gynecology, Inonu University Faculty of Medicine, Malatya, Turkey, dryavuzsimsek@gmail.com.



The current study investigated the potential therapeutic efficiency of atosiban, an oxytocin receptor antagonist, in an experimental endometriosis model.


Endometriosis was surgically induced in 35 female rats during estrus. Four weeks after this procedure, relaparotomy was performed. The viability and dimensions of the endometriosis foci were recorded. Rats were then randomly divided into three groups. In the first group (n = 8), a daily dose of 0.2 ml 0.9 % NaCl was injected intraperitoneally (i.p.) (control cases). In the second and third groups (n = 8 and n = 8), 0.5 mg/kg/day i.p. atosiban and 1 mg/day i.p. diltiazem were given, respectively. At the end of the treatment, laparotomy was performed, and the dimensions of the endometriosis foci were recorded. The endometrial implants were processed for histological and immunohistochemical studies. The volumes of endometriotic implants were measured, and immunohistochemical analyses were performed, and compared between the groups.


After the treatment with atosiban, volumes of endometriotic implants decreased significantly. Proliferating cell nuclear antigen expression levels were significantly reduced in the atosiban and diltiazem groups compared with the control group.


In a rat endometriosis model, atosiban, an agent used for the first time for the medical treatment of endometriosis, has shown significant therapeutic efficiency.

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