Indian J Pharmacol. 2010 Jun;42(3):174-7.

Expression of TNF-α and RANTES in drug-induced human gingival overgrowth.

Subramani T, Dhanaraj L, Senthilkumar K, Periasamy S, Abraham G, Rao S.

Department of Periodontics, Sri Ramachandra Dental College and Hospital, Porur, Chennai – 600 116, India.

OBJECTIVES: Regulated on activation, normal T cell expressed and secreted (RANTES) is a chemokine that is produced by fibroblasts, lymphoid and epithelial cells of the mucosa in response to various external stimuli. RANTES expression has been demonstrated in a variety of diseases characterized by inflammation, including asthma, transplantationassociated accelerated atherosclerosis, endometriosis and fibrosis. RANTES mRNA is quickly up-regulated by tumor necrosis factor (TNF)-α stimulation. Cyclosporine A (CsA) is widely used in organ transplant patients, often causing various side-effects including gingival overgrowth, which is fibrotic in nature. This study was carried out to assess the mRNA expression of TNF-α and RANTES in healthy individual, chronic periodontitis and CsAinduced gingival overgrowth tissues.

MATERIALS AND METHODS: Gingival tissue samples were collected from chronic periodontitis, CsAinduced gingival overgrowth patients and healthy individuals. Total RNA was isolated and reverse transcription polymerase chain reaction (RT-PCR) was performed for TNF-α and RANTES expression.

RESULTS: The results suggest that CsAinduced gingival overgrowth tissues expressed significantly increased TNF-α and RANTES compared to control and chronic periodontitis.

CONCLUSION: The findings of the present study suggest that CsA can modify the expression of TNF-α and RANTES in drug-induced human gingival overgrowth.

Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2010 Sep;35(9):990-4.

Effect of oxidative stress and apoptosis in granulosa cells on the outcome of IVF-ET.

[Article in Chinese]

Liu J, Li Y.

Reproductive Center, Department of Obstetrics and Gynaecology, Xiangya Hospital, Central South University, Changsha 410008; Reproductive Center, Third Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.

Objective To examine the association among malondialdehyde (MDA), superoxide dismutase (SOD) and incidence of apoptosis of granulosa cells in follicular fluid with the outcome of in vitro fertilization-embryo transfer (IVF-ET). Methods We recruited 51 women undergoing an IVF-ET programme for tubal factor infertility. The women with endometriosis or endocrine diseases and those with male factor infertility were excluded. All the 51 patients underwent a long gonadotropin-releasing hormone (GnRH) agonist protocol for pituitary downregulation followed by controlled ovarian hyperstimulation with rFSH. Granulosa cells were isolated from all aspirated follicular fluid using gradient centrifugation at oocyte retrieval. The level of MDA and the activity of the SOD were measured by the thiobarbituric acid(TBA)and the chemiluminescence method, respectively. The apoptosis was studied by flow cytometry using propidium iodide. Results Twenty-six out of the 51 patients (51.0%) were pregnant after IVF-ET. Non-pregnant patients showed significantly higher MDA level [(1.7±0.72)nmol/(g.prot) vs. (1.1±0.56) nmol/(g.prot), P<0.05)], higher incidence of apoptosis (24.8%±6.57% vs.19.0%±5.59%, P<0.05) and lower SOD level [(3.5±1.08)*10(3)NU/(g.prot) vs. (4.4±0.99)*10(3)NU/(g.prot), P<0.05)] in the granulose cells and lower good-embryo rate (54.9±20.22% vs. 65.9±16.16%,P<0.05) compared with the pregnant patients. No correlation was detected among SOD and the number of retrieved oocytes, oocyte maturity, embryo quality, fertilization, or cleavage. A significant negative correlation was detected between MDA and fertilization rate (r=-0.425, P=0.002).No significant correlation was detected between MDA and age,the number of retrieved oocytes, oocyte maturity, cleavage, or good-embryo rate. A significant negative correlation was detected between the incidence of apoptosis and the number of retrieved oocytes(r=-0.286, P=0.042), mature oocytes (r=-0.330, P=0.020)and good-embryo rate(r=-0.311, P=0.026). There was significant negative correlation between MDA and SOD levels(r=-0.471, P<0.001); and significant positive correlation between MDA level and incidence of apoptosis(r=0.475, P<0.001).Conclusion Oxidative stress may induce apoptosis in granulose cells and subsequently lower oocyte quality and lead to poor outcome of IVF-ET.

Fertil Steril. 2010 Sep 24. [Epub ahead of print]

Laparoscopic therapy for endometriosis and vascular entrapment of sacral plexus.

Possover M, Schneider T, Henle KP.

Department of Surgical Gynecology and Neuropelveology, Hirslanden Clinic, Zurich, Switzerland.

OBJECTIVE: To report our experience with endopelvic causes for sacral radiculopathies and sciatica.

DESIGN: Prospective cohort study.

SETTING: Tertiary referral advanced laparoscopic gynecology and neuropelveologic unit.

PATIENT(S): Two hundred thirteen women who underwent laparoscopic management of sacral radiculopathy (sciatica, pudendal, gluteal pain) of unknown genesis in the period between November 2004 and February 2010.

INTERVENTION(S): Selective, clinically oriented, laparoscopic exploration of the sacral plexus with nerve decompression.

MAIN OUTCOME MEASURE(S): Complication rates and the short-term cure at 6-month follow-up with use of the Visual Analogue Scale.

RESULT(S): Laparoscopic exploration showed isolated endometriosis of the sciatic nerve in 27 patients, deeply infiltrating parametric endometriosis with sacral plexus infiltration in 148 patients, sacral plexus vascular entrapment in 37 patients, and pyriformis syndrome in one patient. A reduction in mean ± SEM) Visual Analogue Scale score of patient pain from 7.7 (± 1.16; range 6-10) before surgery to 2.6 (± 1.77; range 0-6) at 6-month follow-up was obtained for sacral plexus endometriosis and from 6.6 (± 1.43; range 5-9) to 1.5 (± 1.27; range 0-4) for vascular entrapment.

CONCLUSION(S): In patients with chronic pelvic pain, preoperative anamnesis and examination should include evaluation of symptoms of sacral radiculopathies (pudendal, gluteal pain) and sciatic neuralgia. In patients with sacral radiculopathy or sciatica of unknown genesis, suspicion of endopelvic pathology such as endometriosis or vascular entrapment must be raised, and laparoscopic exploration of the sacral plexus and/or sciatic nerve is then advisable.

Copyright © 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Minim Invasive Ther Allied Technol. 2010 Oct;19(5):298.

Editorial comment: Laparoscopic ureteroneocystomy and vesicopsoas hitch for infiltrative endometriosis.

Rassweiler J.

Comment on:

Minim Invasive Ther Allied Technol. 2010 Oct;19(5):292-7.

Laparoscopic ureteroneocystostomy and vesicopsoas hitch for infiltrative ureteral endometriosis.

Azioni G, Bracale U, Scala A, Capobianco F, Barone M, Rosati M, Pignata G.

Department of Obstetrics and Gynecology, San Camillo Hospital, Via Giovanelli 19, Trento, Italy.

Comment in:

The aim of the study was to assess the safety and efficacy of laparoscopic treatment of distal infiltrative ureteral endometriosis with segmental ureteral resection, ureteroneocystostomy, and vesicopsoas hitch. We performed a retrospective analysis of perioperative data and looked at follow-up outcomes of patients with deep endometriosis with ureteral involvement treated by laparoscopic vesicopsoas hitch. Six patients were treated for left ureteral endometriosis in the study period. Four of those were diagnosed during previous laparoscopies. A ureteroneocystostomy (Lich-Gregoir reimplantation procedure) with vesicopsoas hitch was fashioned laparoscopically in all cases, and a double-J stent was applied intraoperatively. There were no intraoperative or postoperative complications and no cases of extravasation of contrast at cystogram one week after surgery. The median follow-up time was 38 months (range 12-56). All patients had normal renal ultrasound or intravenous pyelogram results at one year follow-up. This study confirmed that laparoscopic ureteroneocystostomy and vesicopsoas hitch is a safe and effective option in the management of distal ureteral endometriosis. In view of the small size of this series, multicenter studies are needed to confirm these conclusions.

Clin Epidemiol. 2010 Aug 9;2:153-70.

Estrogen-related and other disease diagnoses preceding Parkinson’s disease.

Latourelle JC, Dybdahl M, Destefano AL, Myers RH, Lash TL.

Department of Neurology, Boston University School of Medicine, Boston MA, USA;

PURPOSE: Estrogen exposure has been associated with the occurrence of Parkinson’s disease (PD), as well as many other disorders, and yet the mechanisms underlying these relations are often unknown. While it is likely that estrogen exposure modifies the risk of various diseases through many different mechanisms, some estrogen-related disease processes might work in similar manners and result in association between the diseases. Indeed, the association between diseases need not be due only to estrogen-related factors, but due to similar disease processes from a variety of mechanisms.

PATIENTS AND METHODS: All female Parkinson’s disease cases between 1982 and 2007 (n = 12,093) were identified from the Danish National Registry of Patients, along with 10 controls matched by years of birth and enrollment. Conditional logistic regressions (CLR) were used to calculate risk of PD after diagnosis of the estrogen-related diseases, endometriosis and osteoporosis, conditioning on years of birth and enrollment. To identify novel associations between PD and any other preceding conditions, CLR was also used to calculate the odds ratios (ORs) for risk of PD for 202 different categories of preceding disease diagnoses. Empirical Bayes methods were used to identify the robust associations from the over 200 associations produced by this analysis.

RESULTS: We found a positive association between osteoporosis and osteoporotic fractures and PD (OR = 1.18, 95% confidence interval [CI] of 1.08-1.28), while a lack of association was observed between endometriosis and PD (OR = 1.37, 95% CI 0.99-1.90). Using empirical Bayes analyses, 24 additional categories of diseases, likely unrelated to estrogen exposure, were also identified as potentially associated with PD.

CONCLUSION: We identified several novel associations, which may provide insight into common causal mechanisms between the diseases or greater understanding of potential early preclinical signs of PD. In particular, the associations with several categories of mental disorders suggest that these may be early warning signs of PD onset or these diseases (or the causes of these diseases) may predispose to PD.

PLoS One. 2010 Aug 26;5(8):e12381.

Does the KIR2DS5 gene protect from some human diseases?

Nowak I, Majorczyk E, Wiśniewski A, Pawlik A, Magott-Procelewska M, Passowicz-Muszyńska E, Malejczyk J, Płoski R, Giebel S, Barcz E, Zoń-Giebel A, Malinowski A, Tchórzewski H, Chlebicki A, Łuszczek W, Kurpisz M, Gryboś M, Wilczyński J, Wiland P, Senitzer D, Sun JY, Jankowska R, Klinger M, Kuśnierczyk P.

Department of Clinical Immunology, Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wrocław, Poland.

BACKGROUND: KIR2DS5 gene encodes an activating natural killer cell receptor whose ligand is not known. It was recently reported to affect the outcome of hematopoietic stem cell transplantation.

METHODOLOGY/PRINCIPAL FINDINGS: In our studies on KIR2DS5 gene associations with human diseases, we compared the frequencies of this gene in patients and relevant controls. Typing for KIR2DS5 gene was performed by either individual or multiplex polymerase chain reactions which, when compared in the same samples, gave concordant results. We noted an apparently protective effect of KIR2DS5 gene presence in several clinical conditions, but not in others. Namely, this effect was observed in ankylosing spondylitis (p=0.003, odds ratio [OR]=0.47, confidence interval [CI]=0.28-0.79), endometriosis (p=0.03, OR=0.25, CI = 0.07-0.82) and acute rejection of kidney graft (p=0.0056, OR=0.44, CI=0.24-0.80), but not in non-small-cell lung carcinoma, rheumatoid arthritis, spontaneous abortion, or leukemia (all p>0.05). In addition, the simultaneous presence of KIR2DS5 gene and HLA-C C1 allotype exhibited an even stronger protective effect on ankylosing spondylitis (p=0.0003, OR=0.35, CI=0.19-0.65), whereas a lack of KIR2DS5 and the presence of the HLA-C C2 allotype was associated with ankylosing spondylitis (p=0.0017, OR=1.92, CI=1.28-2.89), whereas a lack of KIR2DS5 and presence of C1 allotype was associated with rheumatoid arthritis (p=0.005, OR=1.47, CI=1.13-1.92). The presence of both KIR2DS5 and C1 seemed to protect from acute kidney graft rejection (p=0.017, OR=0.47, CI=0.25-0.89), whereas lack of KIR2DS5 and presence of C2 seemed to favor rejection (p=0.0015, OR=2.13, CI=1.34-3.37).

CONCLUSIONS/SIGNIFICANCE: Our results suggest that KIR2DS5 may protect from endometriosis, ankylosing spondylitis, and acute rejection of kidney graft.

Biol Reprod. 2010 Sep 23. [Epub ahead of print]

Unique Transcriptome, Pathways, and Networks in the Human Endometrial Fibroblast Response to Progesterone in Endometriosis.

Aghajanova L, Tatsumi K, Horcajadas JA, Zamah AM, Esteban FJ, Herndon CN, Conti M, Giudice LC.

Eutopic endometrium in endometriosis has molecular evidence of resistance to progesterone (P(4)) and activation of the PKA pathway in the stromal compartment. To investigate global and temporal responses of eutopic endometrium to P(4), herein, we investigated early (6 h), intermediate (48 h), and late (14 day) transcriptomes, signaling pathways, and networks of human endometrial stromal fibroblasts from women with endometriosis (hESF(endo)) vs. without disease (hESF(nonendo)). Endometrial biopsies were obtained from subjects with and without mild peritoneal endometriosis (n = 4 per group), and hESF were isolated and treated with P(4) (1 µM) +E(2), (10 nM), E(2) alone (10 nM) or vehicle for up to 14 days. Total RNA was subjected to microarray analysis using the Gene 1.0 ST Affymetrix platform, analyzed by bioinformatic algorithms, and data were validated by QPCR and ELISA. The results reveal unique kinetic expression of specific genes and unique pathways, distinct biological and molecular processes, and signaling pathways and networks during the early, intermediate, and late responses to P(4) in hESF(nonendo) and hESF(endo), although a blunted response to P(4) was observed in the latter. The normal response of hESF to P(4) involves a tightly regulated kinetic cascade involving key components in the progesterone receptor and MAPK signaling pathways that result in inhibition of E(2)-mediated proliferation and eventual differentiation to the decidual phenotype, and this is not established in the early response to P(4) of hESF(endo). The abnormal P(4) responsiveness of this cell type may contribute to compromised embryonic implantation and infertility in women with endometriosis.

Fertil Steril. 2010 Sep 22. [Epub ahead of print]

Effects of prostaglandin E(2) and vascular endothelial growth factor on sperm might lead to endometriosis-associated infertility.

Lee TC, Ho HC.

Institute of Physiological and Anatomical Medicine, Tzu Chi University, Hualien, Taiwan; Department of Obstetrics and Gynecology, Yuli Veterans Hospital, Hualien, Taiwan.

Significantly higher levels of prostaglandin E(2) and vascular endothelial growth factor were associated with the severity of endometriosis. In this study, pathologic concentrations of prostaglandin E(2) and vascular endothelial growth factor found in endometriotic women significantly inhibited sperm motility, acrosome reaction, and sperm-oocyte interaction, which might result in endometriosis-associated subfertility/infertility.

Copyright © 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Tech Coloproctol. 2010 Sep 23. [Epub ahead of print]

Perineal endometriosis: a case report and review of the literature.

Odobasic A, Pasic A, Iljazovic-Latifagic E, Arnautalic L, Odobasic A, Idrizovic E, Dervisefendic M, Dedić L.

Surgery Clinic, University Clinical Center Tuzla, Trnovac bb, 75000, Tuzla, Bosnia and Herzegovina,

Endometriosis is the presence of endometrial-like tissue outside the uterine cavity, which most commonly affects peritoneal surfaces, ovaries and uterine ligaments. Even it is quite rare, endometriosis may affect the vulva, vagina, rectovaginal septum or perineal region, generally secondary to obstetric or surgical trauma. In this case report, we present a patient with perineal endometriosis in an episiotomy scar. Diagnostic tools used included transvaginal and endorectal ultrasonography (USG), magnetic resonance imaging (MRI) and biopsy. The endometriotic mass was wide-excised together with episiotomy scar. The recovery was uneventful with excellent functional and esthetic results. Six months after operation, woman is asymptomatic. According to the literature and our own experience, wide excision of endometriotic tissue seems to be the best chance of cure with satisfactory functional results and should be recommended.

Hum Reprod. 2010 Nov;25(11):2840-50. Epub 2010 Sep 21.

Aberrant expression of regulators of cell-fate found in eutopic endometrium is found in matched ectopic endometrium among women and in a baboon model of endometriosis.

Hapangama DK, Turner MA, Drury J, Heathcote L, Afshar Y, Mavrogianis PA, Fazleabas AT.

Division of Perinatal and Reproductive Medicine, University of Liverpool, Liverpool Women’s Hospital, Liverpool, UK.

BACKGROUND We have recently shown that women with endometriosis express an increased amount of telomerase and nucleolin, with concomitant loss of γ-H2AX in eutopic endometrium. To further examine these selected factors that regulate cell fate, in the pathogenesis of endometriosis, we studied the expression of telomerase, nucleolin, proliferating cell nuclear antigen and γ-H2AX in ectopic endometriotic deposits from women, and in matched eutopic and ectopic endometrial tissue from a baboon model of endometriosis. METHODS Ectopic active peritoneal endometriotic lesions were collected from seven symptomatic women. Endometriosis was induced in six baboons by intra-peritoneal autologous inoculation of menstrual endometrium. Eutopic and matched ectopic endometrial tissues were collected prior to and 6, 12 and 15 months after the induction of endometriosis as previously described. Eutopic endometrium was also obtained from eight healthy fertile control baboons. Immunohistochemistry was performed as previously described, and telomerase activity was confirmed using the telomeric repeat amplification protocol assay. RESULTS All active human endometriotic lesions expressed the proliferative markers but showed weak or absent staining for γ-H2AX. A similar expression pattern of these markers was seen in the ectopic lesions of the baboons with induced disease. In these baboons, the eutopic endometrium also showed intense immunoreactivity for all proliferative markers 6-12 months after induction with a parallel loss of γ-H2AX. The opposite staining pattern was seen in eutopic endometrium of healthy animals and in pre-induction endometrium of animals with induced disease. CONCLUSIONS Endometriotic lesions have excess proliferative potential; in baboons, these were present within 12 months of the initiation of the disease. In eutopic tissue, these changes appear to be induced by the development of endometriosis.

Fertil Steril. 2010 Jun 16. [Epub ahead of print]

The vitamin E-binding protein afamin is altered significantly in the peritoneal fluid of women with endometriosis.

Seeber BE, Czech T, Buchner H, Barnhart KT, Seger C, Daxenbichler G, Wildt L, Dieplinger H.

Department of Gynecologic Endocrinology and Reproductive Medicine, Medical University of Innsbruck, Innsbruck, Austria.

The objective of this case-control study of 242 reproductive-age women was to determine the concentration of afamin in the serum and peritoneal fluid of women with and without endometriosis and to test afamin as a diagnostic marker of endometriosis. Afamin levels were altered significantly in the peritoneal fluid of women with endometriosis compared with disease-free controls, correlated with vitamin E levels, and are consistent with increased oxidative stress in the peritoneal cavity of women with endometriosis.

Copyright © 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Arq Bras Endocrinol Metabol. 2010 Aug;54(6):567-71.

Polymorphism of the estrogen receptor β gene is related to infertility and infertility-associated endometriosis.

Zulli K, Bianco B, Mafra FA, Teles JS, Christofolini DM, Barbosa CP.

Departamento de Ginecologia e Obstetrícia, Santo André, SP, Brazil.

OBJECTIVE: To determine the frequency of the estrogen receptor b gene (ERβ) +1730 G/A polymorphism in infertile women with and without endometriosis and controls.

SUBJECTS AND METHODS: Case-control study that included 136 women with endometriosis, 69 women without endometriosis and 209 fertile women as controls. The ERβ gene + 1730 G/A polymorphism was identified by RFLP-PCR (Restriction Fragment Length Polymorphism – Polymerase Chain Reaction).

RESULTS: Genotypes GG, GA and AA of the ERβ gene presented frequencies of 60.3%, 38.2% and 1.5%, respectively, in the women with endometriosis (p < 0.0022). Of the infertile women without endometriosis, 63.8% presented the normal homozygous genotype GG, 30.4% the GA heterozygous genotype, and 5.8% the homozygous mutated genotype AA (p < 0.0275). In the control group, 77.5% presented the normal homozygous genotype GG, 21.1% the heterozygous genotype GA, and 1.4% the homozygous mutated genotype AA.

CONCLUSION: The data suggest that the estrogen receptor β gene (ERβ) +1730 G/A polymorphism can be associated with risk of infertility and endometriosis-associated infertility.

J Surg Res. 2010 Nov;164(1):e77-81. Epub 2010 Aug 15.

Abdominal wall endometrioma; a 10-year experience and brief review of the literature.

Bektaş H, Bilsel Y, Sarı YS, Ersöz F, Koç O, Deniz M, Boran B, Huq GE.

General Surgery Department, Istanbul Training and Research Hospital, Istanbul, Turkey.

BACKGROUND: Abdominal wall endometrioma is a rare condition, which usually develops in a surgical scar of Cesarean section or hysterectomy. Certain factors relating to knowledge of the clinical pattern of this disease make correct diagnosis and treatment difficult. The aim was to identify the different forms of presentation of this disease entity through publishing the results from our experience of surgical management of such lesions.

METHODS: Patients diagnosed with abdominal wall endometrioma over a period of 10 y were identified from the comprehensive surgical database of our institution. The age, parity, symptoms, previous surgeries, initial diagnosis, diagnostic modalities, current operation, and recurrences were surveyed and analyzed.

RESULTS: There were 40 patients with a mean age of 32.3 ± 5.2 y. All of the patients (100%, n = 40) had an abdominal mass in or adjacent to surgical scars. The main symptom was pain, noncyclic (45%, n =18), or cyclic (40%, n = 16) in nature. The mean duration of symptoms was 18.2 ± 23.4 mo. The preoperative diagnosis was correct in 47.5% (n = 19) of the cases. Surgical treatment failed in 3 cases (3/33, 9.1%), and the operations were performed once again.

CONCLUSIONS: Abdominal wall endometriosis may be difficult to diagnose as it is comparatively an unfamiliar entity that has not received its due attention among general surgeons, so far. Therefore, in patients with a palpable subcutaneous mass in or around surgical scars with a history of violation of uterus, a thorough history and physical examination is necessary, and usually sufficient to make correct diagnosis of endometrioma.

Copyright © 2010 Elsevier Inc. All rights reserved.

Steroids. 2010 Sep 21. [Epub ahead of print]

Dienogest, a synthetic progestin, inhibits prostaglandin E(2) production and aromatase expression by human endometrial epithelial cells in a spheroid culture system.

Shimizu Y, Mita S, Takeuchi T, Notsu T, Mizuguchi K, Kyo S.

Pharmaceutical Research Center, Mochida Pharmaceutical Co., Ltd., 722 Jimba-aza-Uenohara, Gotemba, Shizuoka 412-8524, Japan.

Prostaglandin E(2) (PGE(2)) is a major mediator in the pathophysiology, and pathogenesis of gynecological diseases associated with abnormal endometrial disease with proliferation and inflammation, such as endometriosis. In this study, we investigated the effect of dienogest, a selective progesterone receptor agonist, on PGE(2) production and the expression of aromatase, an estrogen synthase, in human immortalized endometrial epithelial cells. Compared with monolayer culture, the cells showed enhanced PGE(2) production and expression of the PGE(2) synthases cyclooxygenase-2 (COX-2), and microsomal prostaglandin E(2) synthase-1 (mPGES-1) in a spheroid culture system. Dienogest inhibited PGE(2) production and this effect was reversed by RU486, a progesterone receptor antagonist. Dienogest inhibited the PGE(2) synthases mRNA and protein expression, and the nuclear factor-κB activation. Moreover, the suppressive effect of dienogest on PGE(2) production was sustained 24h after the drug was withdrawn. Dienogest but not COX inhibitors inhibited aromatase expression. These results suggest that progesterone receptor activation reduces the gene expressions of COX-2, mPGES-1, and aromatase. Our findings suggest that the pharmacological mechanism of dienogest includes the direct inhibition of PGE(2) synthase and aromatase expression and may contribute to the therapeutic effect on the progression of endometriosis.

Copyright © 2010 Elsevier Inc. All rights reserved.

Fertil Steril. 2010 Sep 16. [Epub ahead of print]

Aberrant expression of the pluripotency marker SOX-2 in endometriosis.

Götte M, Wolf M, Staebler A, Buchweitz O, Kiesel L, Schüring AN.

Department of Gynecology and Obstetrics, University of Münster, Medical Center, Münster, Germany.

Expression of the pluripotency factors SOX-2, OCT-4, KLF-4, and NANOG was analyzed by quantitative real-time polymerase chain reaction, immunohistochemistry, and immunofluorescence microscopy in the endometrium, myometrium, and endometriotic tissue of 36 patients. Aberrant expression of SOX-2 may indicate a stem cell origin of endometriosis, whereas the presence of all progenitor markers in endometrial tissue marks the endometrium as a potential source for induced pluripotent stem cell generation.

Copyright © 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Ulus Travma Acil Cerrahi Derg. 2010 Jul;16(4):371-2.

Scar endometriosis in the rectus abdominis muscle.

[Article in Turkish]

Barlas D, Bozkurt S, Kaya MA, Celik F.

4th Department of General Surgery, Göztepe Training and Research Hospital, Istanbul, Turkey.

Endometriosis is defined as the presence of ectopic functional endometrial tissue outside the uterine cavity. The most common locations are within the pelvis. Unusual sites ofendometriosis outside the pelvis have been reported, including the bladder, intestine, appendix, surgical scars, hernia sac, lung, kidney, and extremities. The diagnosis of scar endometriosis is usually not difficult and is based on history and physical examination. We report here two cases who developed endometriosis on the abdominal wall in the rectus abdominis muscle and were treated with local excisions.

Surg Endosc. 2010 Sep 17. [Epub ahead of print]

Laparoscopic ileocecal resection for bowel endometriosis.

Ruffo G, Stepniewska A, Crippa S, Serboli G, Zardini C, Steinkasserer M, Ceccaroni M, Minelli L, Falconi M.

Department of Surgery, Ospedale Sacro Cuore, Via Sempreboni, 5, 37024, Negrar, VR, Italy,

BACKGROUND: Ileocecal endometriosis is a very rare entity, and its diagnosis is usually made during surgery for other endometriosis sites or, rarely, because of direct complications of ileal involvement. This study was designed to analyze perioperative and long-term outcomes after bowel resection for ileocecal endometriosis.

METHODS: All patients who underwent surgery for ileocecal endometriosis between October 2004 and January 2008 were prospectively collected and analyzed.

RESULTS: Thirty-one women (median age, 34 (range, 25-40) years) were identified. Ileocecal endometriosis was diagnosed during surgery in all patients, and it was associated with colorectal endometriosis in 29 patients (94%). All patients underwent laparoscopic ileocecal resection with no laparotomic conversion. Rectosigmoid or rectal resections was associated in 28 patients (90%) and nodulectomy for sigmoid endometriosis in 1 patient. Median duration of surgery was 301 (range, 90-480) min. Other associated surgical procedures included total hysterectomy (n = 3, 14%), ureterolysis (n = 7, 23%), excision of vesical (n = 4, 13%), vaginal (n = 8, 26%), and parametrial (n = 3, 14%) nodules. There was no mortality. Four patients (13%) required blood transfusions and one a reoperation for bleeding. In a patient who performed ureterolysis, a ureteral fistula occurred. The median hospital stay was 7 (range, 5-18) days. Long-term (>12 months) follow-up data were available for 18 patients. After a median follow-up of 27 months, in 12 of 18 patients (67%) defecation after surgery was normal. Only one patient developed recurrence, which is under medical treatment.

CONCLUSIONS: Laparoscopic ileocecal resection is safe and feasible and should be considered as part of surgery for endometriosis with radical intent.

World J Emerg Surg. 2010 Sep 16;5:27.

Acute small bowel obstruction secondary to intestinal endometriosis, an elusive condition: a case report.

Slesser AA, Sultan S, Kubba F, Sellu DP.

Department of Surgery, Ealing Hospital, Uxbridge Road, Southall, Middlesex, UK.

BACKGROUND: Endometriosis is a benign condition affecting females of reproductive age. Although intestinal endometriosis is common it is rare for the condition to manifest as an acute bowel obstruction secondary to ileocaecal and appendicular endometriosis. This case is important to report as it highlights the diagnostic difficulty this particular condition presents to an emergency surgeon.

CASE PRESENTATION: We present the case of a 33 year old female of Asian origin who presented with symptoms and signs of an acute small bowel obstruction. A right hemicolectomy for suspected malignancy was performed with an ileocolic anastomosis. Histological examination demonstrated extensive endometriosis of the appendix and ileocaecal junction.

CONCLUSION: Enteric endometriosis should be considered as a differential diagnosis when assessing females of reproductive age with acute small bowel obstruction. A high index of suspicion is required to arrive at a diagnosis of this elusive condition.

Mol Med. 2010 Sep 14. [Epub ahead of print]

Insulin-like growth factor-1Ec (MGF) expression in eutopic and ectopic endometrium: characterization of the MGF E peptide actions in vitro.

Milingos DS, Philippou A, Armakolas A, Papageorgiou E, Sourla A, Protopapas A, Liapi A, Antsaklis A, Mastrominas M, Koutsilieris M.

Department of Experimental Physiology, Medical School, National & Kapodistrian University of Athens, Goudi-Athens, Greece.

The transcription of the insulin-like growth factor 1 (igf-1) gene generates 3 mRNA isoforms, namely the IGF-1Ea, IGF-1Eb and IGF-1Ec (or MGF). Herein we have analyzed the expression of IGF-1 isoforms in eutopic and ectopic endometrium (red lesions and endometriotic cyst) of women with endometriosis and we have characterized the actions of a synthetic MGF E peptide on KLE cells. Our data documented that all 3 igf-1 gene transcripts are expressed in the stromal cells of the eutopic and ectopic endometrium, however, endometriotic cysts contained significantly lower IGF-1 isoforms expression, both at the mRNA and protein level, as it was shown using semi-quantitative PCR and immunohistochemical (IHC) methods. In addition, the glandular cells of the eutopic endometrium did not express any of the IGF-1 isoforms; however, the glandular cells of the ectopic endometrium (red lesions) did express the IGF-1Ec at mRNA and protein level. Furthermore, synthetic MGF E peptide, which comprised the last 24 aa of the MGF, stimulated the growth of the KLE cells. Experimental silencing of the type 1 IGF receptor (IGF-1R) and insulin receptor (IR) expression of KLE cells (siRNA knock out methods) did not alter the mitogenic action of the synthetic MGF E peptide revealing that MGF E peptide stimulates the growth of KLE cells via an IGF-1R-independent and IR-independent mechanism. These data suggest that IGF-1Ec transcript might generate, apart from mature IGF-1 peptide, another post-translational bioactive product which may have an important role in endometriosis pathophysiology.

J Hum Genet. 2010 Sep 16. [Epub ahead of print]

Meta-analysis of genome-wide association scans for genetic susceptibility to endometriosis in Japanese population.

Adachi S, Tajima A, Quan J, Haino K, Yoshihara K, Masuzaki H, Katabuchi H, Ikuma K, Suginami H, Nishida N, Kuwano R, Okazaki Y, Kawamura Y, Sasaki T, Tokunaga K, Inoue I, Tanaka K.

Department of Obstetrics and Gynecology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.

To identify susceptibility genes for endometriosis in Japanese women, genome-wide association (GWA) analysis was performed using two case-control cohorts genotyped with the Affymetrix Mapping 500K Array or Genome-Wide Human SNP Array 6.0. In each of the two array cohorts, stringent quality control (QC) filters were applied to newly obtained genotype data, together with previously analyzed data from the Japanese Integrated Database Project. After QC-based filtering of samples and single nucleotide polymorphisms (SNPs) in each cohort, 282 838 SNPs in both genotyping platforms were tested for association with endometriosis using a meta-analysis of the two GWA studies with 696 patients with endometriosis and 825 controls. The meta-analysis revealed that a common susceptibility locus conferring a large effect on the disease risk was unlikely. On the other hand, an excess of SNPs with P-values <10(-4) (36 vs 28 SNPs expected by chance) was observed in the meta-analysis. Of note, four of the top five SNPs with P-values <10(-5) were located in and around IL1A (interleukin 1α), which might be a functional candidate gene for endometriosis. Further studies with larger case-control cohorts will be necessary to elucidate the genetic risk factors.Journal of Human Genetics advance online publication, 16 September 2010; doi:10.1038/jhg.2010.118.

Biol Reprod. 2010 Sep 15. [Epub ahead of print]

Resveratrol Inhibits Development of Experimental Endometriosis In Vivo and Reduces Endometrial Stromal Cell Invasiveness In Vitro.

Bruner-Tran K, Osteen KG, Taylor HS, Sokalska A, Haines K, Duleba AJ.

Endometriosis is a common gynecologic disorder characterized by ectopic attachment and growth of endometrial tissues. Resveratrol is a natural polyphenol with anti-proliferative and anti-inflammatory properties. To study the effects of resveratrol on human endometriotic implants in a nude mouse model and to examine its impact on human endometrial stromal (HES) cell invasiveness in vitro. Human endometrial tissues were obtained from healthy donors. Endometriosis was established in oophorectomized nude mice by intraperitoneal injection of endometrial tissues. Mice were treated with E (8 mg, silastic capsule implants) alone (N = 16) or with resveratrol (6 mg/mouse; N = 20) for 10-12 and 18-20 days beginning 1 day after tissue injection. Mice were sacrificed and endometrial implants were evaluated. A matrigel invasion assay was used to examine the effects of resveratrol on HES cells. Number and size of endometriotic implants in vivo and matrigel invasion in vitro. Resveratrol decreased the number endometrial implants per mouse by 60% (P < 0.001) and the total volume of lesions per mouse by 80% (P < 0.001). Resveratrol (10-30 µM) also induced a concentration-dependent reduction of invasiveness of HES by up to 78% (P < 0.0001). Resveratrol inhibits development of endometriosis in the nude mouse and reduces invasiveness of HES cells. These observations may aid in the development of novel treatments of endometriosis.

Am Fam Physician. 2010 Sep 15;82(6):621-8.

Contraception choices in women with underlying medical conditions.

Bonnema RA, McNamara MC, Spencer AL.

Department of Internal Medicine, University of Nebraska Medical Center, Omaha, Nebraska 68198-5185, USA.

Primary care physicians often prescribe contraceptives to women of reproductive age with comorbidities. Novel delivery systems (e.g., contraceptive patch, contraceptive ring, single-rod implantable device) may change traditional risk and benefit profiles in women with comorbidities. Effective contraceptive counseling requires an understanding of a woman’s preferences and medical history, as well as the risks, benefits, adverse effects, and contraindications of each method. Noncontraceptive benefits of combined hormonal contraceptives, such as oral contraceptive pills, include regulated menses, decreased dysmenorrhea, and diminished premenstrual dysphoric disorder. Oral contraceptive pills may be used safely in women with a range of medical conditions, including well-controlled hypertension, uncomplicated diabetes mellitus, depression, and uncomplicated valvular heart disease. However, women older than 35 years who smoke should avoid oral contraceptive pills. Contraceptives containing estrogen, which can increase thrombotic risk, should be avoided in women with a history of venous thromboembolism, stroke, cardiovascular disease, or peripheral vascular disease. Progestin-only contraceptives are recommended for women with contraindications to estrogen. Depo-Provera, a long-acting injectable contraceptive, may be preferred in women with sickle cell disease because it reduces the frequency of painful crises. Because of the interaction between antiepileptics and oral contraceptive pills, Depo-Provera may also be considered in women with epilepsy. Implanon, the single-rod implantable contraceptive device, may reduce symptoms of dysmenorrhea. Mirena, the levonorgestrel-containing intrauterine contraceptive system, is an option for women with menorrhagia, endometriosis, or chronic pelvic pain.

ScientificWorldJournal. 2010 Sep 1;10:1714-22.

Endometrioid adenocarcinoma in the native ureter of a renal transplant patient: case report and review of the literature.

Healy KA, Carney KJ, Osunkoya A.

Department of Urology, Emory University School of Medicine, Atlanta, GA, USA.

Endometriosis is characterized by endometrial-like tissue outside the uterus, primarily on the pelvic peritoneum, ovaries, and rectovaginal septum, and, in rare cases, within the urinary tract (1-3%). Although endometriosis is a benign condition, malignant transformation of endometriosis is a well-described phenomenon. Malignancies arising in endometriosis are uncommon at extragonadal pelvic sites. A case of endometrioid adenocarcinoma in the native ureter of a postmenopausal renal transplant patient presented with painless gross hematuria and hydroureteronephrosis. The patient had a history of total abdominal hysterectomy and bilateral salpingo-oophrectomy 14 years prior for menorrhagia and had since been on unopposed estrogen replacement therapy. Workup revealed a filling defect in the native left mid-ureter secondary to a large 2.5-cm ureteral tumor. Endoscopic biopsies of the native left ureteral mass showed endometrioid adenocarcinoma, grade II-III. The patient ultimately underwent an open native left nephroureterectomy and temporary diverting colostomy. Final pathology confirmed endometrioid adenocarcinoma, grade II-III, arising in a background of endometriosis with negative perirectal lymph nodes. This case of ureteral endometrioid adenocarcinoma highlights the importance of obtaining a careful history and maintaining a high index of suspicion for malignant degeneration, especially in the context of hyperestrogenism.

Reproduction. 2010 Sep 14. [Epub ahead of print]

Extracellular matrix metalloproteinase inducer (EMMPRIN) expression in the baboon endometrium: menstrual cycle and endometriosis.

Braundmeier AG, Fazleabas AT, Nowak RA.

A Braundmeier, Animal Sciences, University of Illinois Urbana Champaign, Urbana , 61801, United States.

Extracellular matrix metalloproteinase inducer (EMMPRIN) regulates tissue remodeling through matrix metalloproteinases (MMPs). In human and non-human primates endometrial remodeling is important for menstruation and the pathogenesis of endometriosis. We hypothesized that as in humans, EMMPRIN and MMPs are expressed in the endometrium of cycling baboons and their expression is hormonally regulated by ovarian hormones but endometriosis disrupts this regulation. EMMPRIN expression was evaluated in baboon endometrium by q-PCR and immunohistochemistry. In control cycling endometrium EMMPRIN mRNA levels were highest in late secretory tissue. EMMPRIN protein localized to glandular epithelial cells during the proliferative phase whereas secretory tissues expressed EMMPRIN in glandular and luminal epithelium with weak stromal staining. Several MMPs were differentially expressed throughout the menstrual cycle with highest levels found during menstruation. In ovariectomized animals EMMPRIN endometrial mRNA levels were highest with treatment of both estrogen and progesterone compared to only estrogen. Estrogen alone resulted in EMMPRIN protein localization primarily in the endometrial glandular epithelia while estrogen and progesterone treatment displayed EMMPRIN protein localization in both glandular and stromal cells. Exogenous hormone treatment resulted in differential expression patterns of all MMPs compared to control cycling animals. In the eutopic endometrium of endometriotic animals EMMPRIN mRNA levels and protein were elevated early but decreased later in disease progression. Endometriosis elevated the expression of all MMPs except MMP-7 compared to control animals. In baboons, EMMPRIN and MMP endometrial expression is regulated by both ovarian hormones and their expression patterns are dysregulated in endometriotic animals.

Ann N Y Acad Sci. 2010 Sep;1205:207-13. doi: 10.1111/j.1749-6632.2010.05656.x.

Endometriosis and assisted reproduction techniques.

Härkki P, Tiitinen A, Ylikorkala O.

Department of Obstetrics and Gynecology, Helsinki University Central Hospital, Helsinki, Finland.

Endometriosis-associated infertility is poorly treatable with various forms of surgery. Therefore, assisted reproduction techniques (ARTs), such as controlled ovarian hyperstimulation, intrauterine insemination, or in vitro fertilization, are commonly used for endometriosis-associated infertility. Endometriosis impairs the efficacy of in vitro fertilization. There is no evidence that ovulation suppression before ART would enhance the efficacy of ART. Resection of minimal/mild endometriosis and/or restoration of the normality of pelvic anatomy may enhance the efficacy of ART, but aggressive ovarian surgery should be avoided, because it reduces the ovarian reserves and the likelihood of pregnancy after ART. The outcome of ART pregnancy is not affected by the history of endometriosis, but the presence of endometrioma may predispose to preterm birth or fetal growth retardation in ART-induced pregnancies. As a whole, infertility due to endometriosis is best treated with various forms of ART, and the earlier clinicians apply these techniques, the more likely pregnancy may ensue.

© 2010 New York Academy of Sciences.

Rev Assoc Med Bras. 2010 Jul-Aug;56(4):467-71.

Epidemiological and clinical aspects of pelvic endometriosis: series of cases.

[Article in Portuguese]

Bellelis P, Dias JA Jr, Podgaec S, Gonzales M, Baracat EC, Abrão MS.

Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP.

OBJECTIVE: To describe clinical and epidemiological aspects of patients with pelvic endometriosis who were operated in our service.

METHODS: A retrospective study was made of 892 patients submitted to laparoscopy with histological confirmation of diagnosis of endometriosis.

RESULTS: The mean age was 33.2 ± 6.3 years and 78.7% were Caucasian. We found that 76.9% of women had higher education. 56.5% of patients were nulliparous and 62.2% reported dysmenorrhea as the main complaint. Chronic pelvic pain was the most prevalent symptom, followed by deep dyspareunia, mentioned by 56.8% and 54.7% of patients, respectively. Infertility was reported by 39.8% of the 892 patients.

CONCLUSION: Endometriosis is a disease diagnosed in the 4th decade of life, of patients who have multiple complaints . They must always be questioned to properly orient diagnosis and monitor results of treatment.

J Robot Surg. 2010 Sep;4(3):167-175. Epub 2010 Aug 10.

Comparison of minimally invasive surgical approaches for hysterectomy at a community hospital: robotic-assisted laparoscopic hysterectomy, laparoscopic-assisted vaginal hysterectomy and laparoscopic supracervical hysterectomy.

Giep BN, Giep HN, Hubert HB.

The study reported here compares outcomes of three approaches to minimally invasive hysterectomy for benign indications, namely, robotic-assisted laparoscopic (RALH), laparoscopic-assisted vaginal (LAVH) and laparoscopic supracervical (LSH) hysterectomy. The total patient cohort comprised the first 237 patients undergoing robotic surgeries at our hospital between August 2007 and June 2009; the last 100 patients undergoing LAVH by the same surgeons between July 2006 and February 2008 and 165 patients undergoing LAVHs performed by nine surgeons between January 2008 and June 2009; 87 patients undergoing LSH by the same nine surgeons between January 2008 and June 2009. Among the RALH patients were cases of greater complexity: (1) higher prevalence of prior abdominopelvic surgery than that found among LAVH patients; (2) an increased number of procedures for endometriosis and pelvic reconstruction. Uterine weights also were greater in RALH patients [207.4 vs. 149.6 (LAVH; P < 0.001) and 141.1 g (LSH; P = 0.005)]. Despite case complexity, operative time was significantly lower in RALH than in LAVH (89.9 vs. 124.8 min, P < 0.001) and similar to that in LSH (89.6 min). Estimated blood loss was greater in LAVH (167.9 ml) than in RALH (59.0 ml, P < 0.001) or LSH (65.7 ml, P < 0.001). Length of hospital stay was shorter for RALH than for LAVH or LSH. Conversion and complication rates were low and similar across procedures. Multivariable regression indicated that LAVH, obesity, uterine weight ≥250 g and older age predicted significantly longer operative time. The learning curve for RALH demonstrated improved operative time over the case series. Our findings show the benefits of RALH over LAVH. Outcomes in RALH can be as good as or better than those in LSH, suggesting the latter should be the choice primarily for women desiring cervix-sparing surgery.

Radiographics. 2010 Sep;30(5):1235-49.

Transvaginal US after bowel preparation for deeply infiltrating endometriosis: protocol, imaging appearances, and laparoscopic correlation.

Chamié LP, Pereira RM, Zanatta A, Serafini PC.

Department of Diagnostic Imaging, Fleury Medicina e Saúde, Rua Cincinato Braga, São Paulo, Brazil.

Deeply infiltrating endometriosis (DIE) is a common gynecologic disease that is characterized by a difficult and delayed diagnosis. Radiologic mapping of the DIE lesion sites is crucial for case management, patient counseling, and surgical planning. Transvaginal ultrasonography (US) is the initial imaging modality for investigating DIE and has been the focus of several recent studies. DIE typically manifests at imaging as hypoechogenic nodules throughout the affected sites and thickening of the intestinal wall, with some lesions showing a mixed pattern due to cystic areas. Transvaginal US performed after bowel preparation improves the ability to diagnose intestinal lesions and provides invaluable details, including which layers of the intestine are affected and the distance between the lesion and the anal border. It is vital that radiologists be familiar with the technical aspects of this modality and with the US manifestations of DIE lesions. Transvaginal US performed after bowel preparation should be the first-line imaging modality for the evaluation of women with suspected endometriosis.

Hum Reprod Update. 2010 Sep 10. [Epub ahead of print]

Oral contraceptives and risk of endometriosis: a systematic review and meta-analysis.

Vercellini P, Eskenazi B, Consonni D, Somigliana E, Parazzini F, Abbiati A, Fedele L.

Clinica Ostetrica e Ginecologica I, Istituto ‘Luigi Mangiagalli’, Università Statale di Milano, Fondazione IRCCS ‘Ca’ Granda’ – Ospedale Maggiore Policlinico, Via Commenda 12, Milan 20122, Italy.

BACKGROUND Combined oral contraceptives (OCs) inhibit ovulation, substantially reduce the volume of menstrual flow and may hypothetically interfere with implantation of refluxed endometrial cells. The aim of this review is to establish if OC use influences the risk of endometriosis. METHODS We performed a MEDLINE search to identify all studies published in the last four decades (January 1970 to January 2010) in the English language on the relationship between OC exposure and risk of endometriosis. Two authors abstracted data on standardized forms. RESULTS We identified 608 potentially relevant studies and 18 studies (6 cross-sectional, 7 case-control and 5 cohort) were selected. Pooling of the results derived from all the included reports independently from study design, yielded a common relative risk of 0.63 [95% confidence interval (CI), 0.47-0.85] for current OC users, 1.21 (95% CI, 0.94-1.56) for past users and 1.19 (95% CI, 0.89-1.60) for ever users. Methodological drawbacks, such as uncertain temporal relationship between exposure and outcome in cross-sectional studies and suboptimal selection of controls in case-control studies, limit the quality of the available evidence. CONCLUSIONS The risk of endometriosis appears reduced during OC use. However, it is not possible to exclude the possibility that the apparent protective effect of OC against endometriosis is the result of postponement of surgical evaluation due to temporary suppression of pain symptoms. Confounding by selection and indication biases may explain the trend towards an increase in risk of endometriosis observed after discontinuation, but further clarification is needed. To date, the hypothesis of recommending OCs for primary prevention of endometriosis does not seem sufficiently substantiated.

Pain. 2010 Sep 10. [Epub ahead of print]

Endocannabinoid involvement in endometriosis.

Dmitrieva N, Nagabukuro H, Resuehr D, Zhang G, McAllister SL, McGinty KA, Mackie K, Berkley KJ.

Program in Neuroscience, Florida State University, Tallahassee, FL 32306, USA.

Endometriosis is a disease common in women that is defined by abnormal extrauteral growths of uterine endometrial tissue and associated with severe pain. Partly because how the abnormal growths become associated with pain is poorly understood, the pain is difficult to alleviate without resorting to hormones or surgery, which often produce intolerable side effects or fail to help. Recent studies in a rat model and women showed that sensory and sympathetic nerve fibers sprout branches to innervate the abnormal growths. This situation, together with knowledge that the endocannabinoid system is involved in uterine function and dysfunction and that exogenous cannabinoids were once used to alleviate endometriosis-associated pain, suggests that the endocannabinoid system is involved in both endometriosis and its associated pain. Herein, using a rat model, we found that CB1 cannabinoid receptors are expressed on both the somata and fibers of both the sensory and sympathetic neurons that innervate endometriosis’s abnormal growths. We further found that CB1 receptor agonists decrease, whereas CB1 receptor antagonists increase, endometriosis-associated hyperalgesia. Together these findings suggest that the endocannabinoid system contributes to mechanisms underlying both the peripheral innervation of the abnormal growths and the pain associated with endometriosis, thereby providing a novel approach for the development of badly-needed new treatments.

Copyright © 2010 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Eur J Obstet Gynecol Reprod Biol. 2010 Sep 8. [Epub ahead of print]

The efficacy and tolerability of short-term low-dose estrogen-only add-back therapy during post-operative GnRH agonist treatment for endometriosis.

Kim NY, Ryoo U, Lee DY, Kim MJ, Yoon BK, Choi D.

Department of Obstetrics and Gynecology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong, Gangnam-gu, Seoul 135-710, Republic of Korea.

OBJECTIVE: To evaluate the efficacy and tolerability of a low-dose estrogen-only regimen as a short-term add-back therapy during post-operative GnRH agonist (GnRHa) treatment of patients with endometriosis.

STUDY DESIGN: Retrospective cohort study. One hundred seventeen women of reproductive age who were treated with post-operative GnRHa after conservative laparoscopic surgery for endometrioma were eligible for this study. The patients were divided into two groups: group A (n=56) received tibolone (2.5mg) between 2002 and 2004 and group B (n=61) received estradiol valerate (1mg) between 2005 and 2007 as an add-back therapy for five months, beginning at the time of the second injection of a GnRHa. The incidence of hypoestrogenic symptoms and the degree of pelvic pain according to a verbal rating scale (VRS) scoring system, the incidence and patterns of uterine bleeding during add-back therapy, the endometrial thickness by ultrasonography two months after the last GnRHa treatment, and the serum CA-125 level were evaluated.

RESULTS: The incidence of uterine bleeding, hypoestrogenic symptoms such as hot flashes and sweating, and pelvic pain did not differ significantly between the two treatment groups. However, the endometrium was thicker in group A than group B (p=0.022). In group B, the frequency of uterine bleeding was lower from the second month after starting add-back therapy than in group A, but without statistical significance (at the sixth month, p=0.086).

CONCLUSION: The low-dose estrogen-only regimen was efficacious and tolerable as a short-term add-back therapy during post-operative GnRHa treatment after surgery for endometriosis.

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