- Email: [email protected]
Changes in bone density in women with endometriosis on leuprolide vs norethindrone treatment
DESIGN: Prospective study at a University teaching hospital. MATERIALS AND METHODS: Plasma was collected from cases (N¼37), and controls (N¼9) at McMaster University Medical Centre. Participants provided informed consent, and completed a questionnaire about demographics, menstrual cycle, and pain. Cases were categorized by ASRM stages by a gynaecological surgeon. BDNF was measured in duplicate using the Emax ELISA (Promega). Circulating BDNF was statistically compared between cases and controls, stages of disease, relation to pain, and menstrual cycle stage by t-test, one-way ANOVA, or linear regression. RESULTS: Circulating BDNF was statistically compared between cases and controls, stages of disease, relation to pain, and menstrual cycle stage by t-test, one-way ANOVA, or linear regression. Circulating BDNF was significantly higher in women with endometriosis than controls (P¼0.014), and was elevated in women with Stage 2 disease as compared to controls (P¼0.006). Circulating BDNF did not positively correlate with self-reported pain scores, but had a tendency towards a correlation in patients with Stage 2 disease (P¼0.101, R2¼0.647). Overall pain scores were significantly higher in cases than controls (P<0.001). In cases, BDNF was unchanged over the menstrual cycle. CONCLUSION: Preliminary results indicate that plasma BDNF may provide a reliable clinical marker for endometriosis, that circulating BDNF may be related to the number of active lesions (red, black) as in early disease, and that that it did not correlate with reported pain or fluctuate over the menstrual cycle in cases, contrary to what has been reported in women without endometriosis. Further studies are required to confirm BDNF as a clinical marker of endometriosis. Supported by: Canadian Institutes of Health Research, Natural Sciences and Engineering Council of Canada. O-333 Wednesday, October 16, 2013 04:30 PM IMPACT OF DEPRESSION ON IMPROVEMENT OF PAIN SYMPTOMS CAUSED BY NORETHINDRONE ACETATE IN WOMEN WITH RECTOVAGINAL ENDOMETRIOSIS. U. Leone Roberti Maggiore, C. Scala, V. Remorgida, P. L. Venturini, S. Ferrero. Department of Obstetrics and Gynecology, San Martino Hospital and National Institute for Cancer Research, University of Genoa, Genoa, Liguria, Italy. OBJECTIVE: To assess the efficacy of norethindrone acetate (NETA) for the treatment of pain symptoms caused by rectovaginal endometriosis in depressed patients (group D) and in non-depressed controls (group N). DESIGN: Open-label assessor-blinded prospective comparative study. MATERIALS AND METHODS: Patients were treated with NETA (2.5 mg/day) for 12 months. Patients completed the Beck Depression Inventory (BDI) at baseline. On the basis of the results of BDI, patients were divided in group N (BDI score < 17) or in group D (BDI score R 17). The investigators were blinded to the depression status. The volume of the rectovaginal nodules was determined by virtual organ computer-aided analysis (VOCAL). The Endometriosis Health Profile-30 (EHP-30) questionnaire was used to assess QoL. The primary endpoint of the study was to evaluate the rate of satisfied patients in the two study groups at the end of treatment. Secondary endpoint was the assessment of the changes in pain symptoms and QoL between the study groups. RESULTS: Forty-seven women with rectovaginal endometriosis were enrolled in the study. At the end of treatment, the percentage decrease in the volume of the nodule similar in the two study groups (p¼0.869). At 12-month follow-up, the rate of satisfied patients was higher in group N than in group D (p<0.05). At baseline, the intensity of dysmenorrhea, deep dyspareunia, non-menstrual pelvic pain and dyschezia was similar in the two study groups. At 1-year follow-up, the intensity of deep dyspareunia and non-menstrual pelvic pain was significantly higher in group D than in group N (p<0.01). The EHP-30 scores were similar at baseline between the two study groups, but they were significantly lower in group N than in group D (p<0.05) at 12-month follow-up. CONCLUSION: Depressed women with rectovaginal endometriosis treated with NETA have decreased improvement in pain symptoms and QoL compared with non-depressed patients. O-334 Wednesday, October 16, 2013 04:45 PM A PROSPECTIVE STUDY OF ADOLESCENT DAIRY CONSUMPTION AND ENDOMETRIOSIS RISK. J. L. Nodler,a H. R. Harris,a,b
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J. E. Chavarro,c,d,e S. A. Missmer.a,c,d aDepartment of Obstetrics, Gynecology, and Reproductive Biology, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA; bDepartment of Nutritional Epidemiology, The National Institute for Environmental Medicine, Karolinska Institutet, Stockholm, Solna, Sweden; cDepartment of Epidemiology, Harvard School of Public Health, Boston, MA; dDepartment of Medicine, Channing Division of Network Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA; eDepartment of Nutrition, Harvard School of Public Health, Boston, MA. OBJECTIVE: Modifiable risk factors such as diet may be important in halting the progression of endometriosis, the prevalence of pain symptoms, and the development of infertility. In adults, total and low-fat dairy foods have been associated with a decreased risk of endometriosis. There is currently no literature on the effect of diet during adolescence on endometriosis diagnosis. The objective of this study was to analyze the relation between dairy consumption in adolescence and subsequent development of endometriosis. DESIGN: Prospective Cohort. MATERIALS AND METHODS: We analyzed 20 years of data collected from 40,524 premenopausal women in the Nurses Health Study II who in 1998 completed a validated 124-item food frequency questionnaire about their high school diet. Cox proportional hazard models adjusted for age, BMI at age 18, smoking, contraceptive use, and physical activity in adolescence, were used to calculate relative risks and 95% confidence intervals (CI). RESULTS: In the 558,785 person-years of follow-up, 2,315 cases of laparoscopically confirmed endometriosis were diagnosed. Women in the highest quintile of total dairy consumption had a 20% lower risk [CI ¼ 0.67-0.95; P-value, test for linear trend (Pt) ¼ 0.002], and those in the highest quintile of high-fat dairy had a 23% lower risk (CI ¼ 0.64-0.92; Pt ¼ 0.001) of endometriosis than those in the lowest quintile. Among women who presented with pain symptoms, those in the highest quintile of total dairy consumption had a 31% lower risk (CI ¼ 0.56-0.84; Pt <0.001) of endometriosis than those in the lowest quintile. CONCLUSION: Consumption of dairy, especially high fat dairy, in adolescence may have a protective effect on the subsequent development of endometriosis. Women who consume greater amounts of dairy in adolescence may be even more unlikely to develop endometriosis with pain symptoms. Supported by: NIH grants HD48544, HD52473, and CA50385.
O-335 Wednesday, October 16, 2013 05:00 PM CHANGES IN BONE DENSITY IN WOMEN WITH ENDOMETRIOSIS ON LEUPROLIDE VS NORETHINDRONE TREATMENT. O. Muneyyirci-Delale,a,b C. Charles,a N. Sinaii,c J. Anopa,a M. Dalloul,a P. Stratton.d aObstetrics and Gynecology, SUNY Downstate Medical Center, Brooklyn, NY; bObstetrics and Gynecology, Kings County Hospital Center, Brooklyn, NY; cBiostatistics & Clinical Epidemiology Service, NIH Clinical Center, Bethesda, MD; dProgram in Reproductive and Adult Endocrinology, NICHD/NIH, Bethesda, MD. OBJECTIVE: To assess changes in bone mineral density (BMD) of women with endometriosis-associated pain undergoing treatment with Leuprolide Acetate Depot form (LD) vs Norethindrone Acetate (NA). DESIGN: Prospective, randomized double-masked clinical trial. MATERIALS AND METHODS: 62 women with endometriosis-associated pain were randomized to receive LD 11.25mg every 3 months or NA 5mg daily for 24 weeks (24W), then all were given NA for another 28 weeks (52W). After 52 weeks of treatment, women were followed for one year (12FU). One woman with arthritis was excluded from analysis. BMD of hip and lumbar spine were measured at entry, 24W, 52W, and 12FU using DEXA (Delphi QDR Series, Hologic Inc). Covariates (BMI, estradiol levels, calcium intake, age and race) were evaluated for potential confounding. Data were analyzed using two-sample and paired t-tests, or analysis of covariance adjusting for any potential confounders, as appropriate. RESULTS: Women were predominantly Black (82%), between age 21 and 47 years with 30 NA and 31 LD. BMD measurements at entry and covariates were similar between groups. Compared to NA women, lumbar
Vol. 100, No. 3, Supplement, September 2013
BMD significantly decreased in LD women from entry to both 24W (p<0.001) and 52W (p¼0.003). Hip BMD from entry also decreased in LD women compared to NA women at 52W (p<0.001). BMD for both groups recovered by 12FU when compared to entry (Lumbar: p¼0.054 and Hip: p¼0.903). BMD for NA use during 12FU had higher hip BMD at 12FU (p¼0.023). CONCLUSION: After one year of treatment with NA, BMD for women was not altered while lumbar spine BMD after LD then NA was significantly lower. This bone loss resolved over the next year. Women on NA were able to continue long-term treatment without experiencing a significant change in BMD. Supported by: NIH: R01-HD043281, Intramural Program, PRAE/NICHD and BCES/CC.
O-336 Wednesday, October 16, 2013 05:15 PM UNRAVELING THE MOLECULR INTERACTIONS BETWEEN PGE2 SIGNALING AND PAIN PATHWAYS IN ENDOMETRIOSIS. J. A. Arosh,a J. Lee,a M. Meagher,b K. Osteen,c K. Bruner-Tran,c S. Banu.a aIntegrative Bioscinecs, Texas A&M University, College Station, TX; bDepartment of Psychology, Texas A&M University, College Station, TX; cDepartment of Obstetrics and Gynecology, Vanderbilt University, Nashville, TN. OBJECTIVE: Prostaglandin E2 (PGE2) is the principal mediator in inflammation and pain hypersensitivity and plays important roles in the pathogenesis of endometriosis. PGE2 produced at the site of inflammation acts on the nociceptors of peripheral terminals through EP1, EP2, EP3, and EP4 receptors. Inhibition of PGE2 biosynthesis using NSAIDs and COX-2 inhibitors has emerged as the main class analgesics. Selective inhibition of PGE2 signaling down-stream of COX-2 may provide an opportunity to inhibit pronociceptive actions of PGE2 in endometriosis. DESIGN: Our working hypothesis is that pharmacological systemic blockade of EP2 and EP4 inhibits growth and innervations of endometriosis and peripheral and central nociceptive mechanisms. MATERIALS AND METHODS: Mixed population of human endometriotic epithelial cells (12Z-GFP) and stromal cells (22B-RFP) were xenografted into the peritoneal cavity Rag2g(c). On day 15 of xenograft, Group-1 (n¼6) mice were served as control. Group-2 (n¼6) mice were treated with EP2 and EP4 inhibitors. Group-3 (n¼6) were served as sham control. On day 30, motor activity of the experimental mice was examined by Digiscan. Then, the mice were euthanized and peritoneal endometriosis lesions were collected. RESULTS: A linear increase of 12Z-GFP or 22B-RFP cells was detected with the in vivo imager. Using a fluorescence stereo microscope, 18-20 lesions were detectable in the peritoneal cavity. Selective inhibition of EP2 and EP4 decreased growth of endometriosis about 50-60%, decreased expression of Protein Gene Product 9.5 (PGP 9.5), Substance P (SP), and Vesicular Monoamine Transporter (VMAT) in endometriosis innervations, and partially restored the motor activity in experimental endometriosis mice. CONCLUSION: These results together indicate that selective inhibition of EP2 and EP4 decreases growth of endometriosis, inhibits innervations of endometriosis and nociceptive pathways, and restores motor activity in endometriosis xenograft mice models. Supported by: 1R21HD066248-01A1 to JAA.
O-337 Wednesday, October 16, 2013 05:30 PM MULTIDETECTOR COMPUTERIZED TOMOGRAPHY ENTEROCLYSIS VERSUS MAGNETIC RESONANCE ENTEROCLYSIS IN THE DIAGNOSIS OF COLORECTAL ENDOMETRIOSIS. S. Ferrero,a U. Leone Roberti Maggiore,a P. L. Venturini,a G. A. Rollandi,b E. Biscaldi.b aDepartment of Obstetrics and Gynecology, San Martino Hospital and University of Genoa, Genoa, Liguria, Italy; bDepartment of Radiology, Galliera Hospital, Genoa, Liguria, Italy. OBJECTIVE: To compare the accuracy of multidetector computerized tomography enteroclysis (MDCT-e) and magnetic resonance enteroclysis
FERTILITY & STERILITYÒ
(MR-e) in determining the presence and the mucosa layer involvement of sigmoid and rectal endometriotic nodules. DESIGN: Single-center, prospective study. MATERIALS AND METHODS: Women with symptoms suggestive of bowel endometriosis underwent MDCT-e and MR-e. After retrograde colonic distension and injection of the intravenous contrast medium, patients were scanned on a 16-row MDCT scanner. MR-e was performed on a 1.5 T magnet using an 8 channels phased array coil; the intestinal distension was achieved by introducing in the rectum 250-300 ml of ultrasonographic gel diluted with saline solution. Radiological findings were compared with surgical and histological results. The McNemar’s test with the Yates continuity correction was used to compare the accuracy of the two techniques in the diagnosis of intestinal endometriosis. RESULTS: Two hundred and sixty patients were enrolled in the study; surgery demonstrated that 176 women (67.7%) had bowel endometriotic nodules. There was no difference in the accuracy of MDCT-e (98.5%) and MR-e (96.9%) in the diagnosis of sigmoid and rectal endometriosis (p ¼ 0.248). The sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio and negative likelihood ratio of MDCT-e and MR-e were respectively 98.3%, 98.8%, 99.4%, 96.5%, 81.59, 0.02 and 97.2%, 96.4%, 98.3%, 94.1%, 26.89, 0.03. MDCT-e accuracy had higher accuracy in determining the presence of endometriotic nodules infiltrating the mucosa layer compared with MR-e (p ¼ 0.041). CONCLUSION: Both MDCT-e and MR-e are accurate in the diagnosis of colorectal endometriosis. MDCT-e is more accurate than MR-e in determining correctly the depth of endometriotic nodule penetration in the intestinal wall.
O-338 Wednesday, October 16, 2013 05:45 PM INTERLEUKIN-1BETA INCREASES EXPRESSION OF TRYPTOPHAN 2,3-DIOXYGENASE AND STIMULATES TRYPTOPHAN METABOLISM IN ECTOPIC ENDOMETRIAL STROMAL CELLS. Y. Urata, Y. Osuga, K. Koga, Y. Hirota, T. Hirata, T. Fujii. Department of Obstetrics and Gynecology, University of Tokyo, Bunkyoku, Tokyo, Japan. OBJECTIVE: Tryptophan 2,3-dioxygenase (TDO) and indoleamine 2,3dioxygenase (IDO) are enzymes that catalyze the first and rate-limiting step of tryptophan degradation (i.e. from tryptophan to kynurenine) and thereby regulate tryptophan levels. Decrease in tryptophan levels inhibits T cell function and contributes to immune tolerance. While IFNg increases IDO expression, a molecule that regulates TDO expression remains to be elucidated. We evaluated the effect of interleukin (IL)-1b, a typical endometriosis-associated cytokine, on TDO expression in ectopic endometrial stromal cells (ESCs). DESIGN: Experimental study. MATERIALS AND METHODS: Under the approval of Institutional Review Board, ovarian endometriomas were obtained from women who had regular menstrual cycles and underwent laparoscopic surgery. ESCs were isolated from ovarian endometriomas. ESCs were treated with IL-1b for 5 hours to examine gene expression, for 24 hours to examine protein expression, and for 48 hours to examine the enzyme activity. Expression levels of TDO mRNA and IDO mRNA in ESCs were determined by quantitative real-time polymerase chain reaction. TDO protein was detected using western blotting. To study the enzyme activity of TDO and IDO, kynurenine concentration in the conditioned medium was measured. RESULTS: IL-1b (1 ng/ml) increased TDO mRNA expression to 6.3-fold of control but had no effect on IDO mRNA expression in ESCs. IL-1b (1 ng/ ml) increased TDO protein to 1.3-fold in ESCs and also increased kynurenine production to 1.9-fold in the conditioned medium. TDO siRNA suppressed the increase in IL-1b-induced kynurenine production. CONCLUSION: IL-1b increased TDO expression and stimulated tryptophan metabolism in ESCs. The IL-1b-induced increase in TDO expression may enhance immune tolerance to promote endometriosis. Supported by: Grants from the Ministry of Health, Labor, and Welfare and the Ministry of Education, Culture, Sports, Science, and Technology of Japan.
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J. E. Chavarro,c,d,e S. A. Missmer.a,c,d aDepartment of Obstetrics, Gynecology, and Reproductive Biology, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA; bDepartment of Nutritional Epidemiology, The National Institute for Environmental Medicine, Karolinska Institutet, Stockholm, Solna, Sweden; cDepartment of Epidemiology, Harvard School of Public Health, Boston, MA; dDepartment of Medicine, Channing Division of Network Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA; eDepartment of Nutrition, Harvard School of Public Health, Boston, MA. OBJECTIVE: Modifiable risk factors such as diet may be important in halting the progression of endometriosis, the prevalence of pain symptoms, and the development of infertility. In adults, total and low-fat dairy foods have been associated with a decreased risk of endometriosis. There is currently no literature on the effect of diet during adolescence on endometriosis diagnosis. The objective of this study was to analyze the relation between dairy consumption in adolescence and subsequent development of endometriosis. DESIGN: Prospective Cohort. MATERIALS AND METHODS: We analyzed 20 years of data collected from 40,524 premenopausal women in the Nurses Health Study II who in 1998 completed a validated 124-item food frequency questionnaire about their high school diet. Cox proportional hazard models adjusted for age, BMI at age 18, smoking, contraceptive use, and physical activity in adolescence, were used to calculate relative risks and 95% confidence intervals (CI). RESULTS: In the 558,785 person-years of follow-up, 2,315 cases of laparoscopically confirmed endometriosis were diagnosed. Women in the highest quintile of total dairy consumption had a 20% lower risk [CI ¼ 0.67-0.95; P-value, test for linear trend (Pt) ¼ 0.002], and those in the highest quintile of high-fat dairy had a 23% lower risk (CI ¼ 0.64-0.92; Pt ¼ 0.001) of endometriosis than those in the lowest quintile. Among women who presented with pain symptoms, those in the highest quintile of total dairy consumption had a 31% lower risk (CI ¼ 0.56-0.84; Pt <0.001) of endometriosis than those in the lowest quintile. CONCLUSION: Consumption of dairy, especially high fat dairy, in adolescence may have a protective effect on the subsequent development of endometriosis. Women who consume greater amounts of dairy in adolescence may be even more unlikely to develop endometriosis with pain symptoms. Supported by: NIH grants HD48544, HD52473, and CA50385.
O-335 Wednesday, October 16, 2013 05:00 PM CHANGES IN BONE DENSITY IN WOMEN WITH ENDOMETRIOSIS ON LEUPROLIDE VS NORETHINDRONE TREATMENT. O. Muneyyirci-Delale,a,b C. Charles,a N. Sinaii,c J. Anopa,a M. Dalloul,a P. Stratton.d aObstetrics and Gynecology, SUNY Downstate Medical Center, Brooklyn, NY; bObstetrics and Gynecology, Kings County Hospital Center, Brooklyn, NY; cBiostatistics & Clinical Epidemiology Service, NIH Clinical Center, Bethesda, MD; dProgram in Reproductive and Adult Endocrinology, NICHD/NIH, Bethesda, MD. OBJECTIVE: To assess changes in bone mineral density (BMD) of women with endometriosis-associated pain undergoing treatment with Leuprolide Acetate Depot form (LD) vs Norethindrone Acetate (NA). DESIGN: Prospective, randomized double-masked clinical trial. MATERIALS AND METHODS: 62 women with endometriosis-associated pain were randomized to receive LD 11.25mg every 3 months or NA 5mg daily for 24 weeks (24W), then all were given NA for another 28 weeks (52W). After 52 weeks of treatment, women were followed for one year (12FU). One woman with arthritis was excluded from analysis. BMD of hip and lumbar spine were measured at entry, 24W, 52W, and 12FU using DEXA (Delphi QDR Series, Hologic Inc). Covariates (BMI, estradiol levels, calcium intake, age and race) were evaluated for potential confounding. Data were analyzed using two-sample and paired t-tests, or analysis of covariance adjusting for any potential confounders, as appropriate. RESULTS: Women were predominantly Black (82%), between age 21 and 47 years with 30 NA and 31 LD. BMD measurements at entry and covariates were similar between groups. Compared to NA women, lumbar
Vol. 100, No. 3, Supplement, September 2013
BMD significantly decreased in LD women from entry to both 24W (p<0.001) and 52W (p¼0.003). Hip BMD from entry also decreased in LD women compared to NA women at 52W (p<0.001). BMD for both groups recovered by 12FU when compared to entry (Lumbar: p¼0.054 and Hip: p¼0.903). BMD for NA use during 12FU had higher hip BMD at 12FU (p¼0.023). CONCLUSION: After one year of treatment with NA, BMD for women was not altered while lumbar spine BMD after LD then NA was significantly lower. This bone loss resolved over the next year. Women on NA were able to continue long-term treatment without experiencing a significant change in BMD. Supported by: NIH: R01-HD043281, Intramural Program, PRAE/NICHD and BCES/CC.
O-336 Wednesday, October 16, 2013 05:15 PM UNRAVELING THE MOLECULR INTERACTIONS BETWEEN PGE2 SIGNALING AND PAIN PATHWAYS IN ENDOMETRIOSIS. J. A. Arosh,a J. Lee,a M. Meagher,b K. Osteen,c K. Bruner-Tran,c S. Banu.a aIntegrative Bioscinecs, Texas A&M University, College Station, TX; bDepartment of Psychology, Texas A&M University, College Station, TX; cDepartment of Obstetrics and Gynecology, Vanderbilt University, Nashville, TN. OBJECTIVE: Prostaglandin E2 (PGE2) is the principal mediator in inflammation and pain hypersensitivity and plays important roles in the pathogenesis of endometriosis. PGE2 produced at the site of inflammation acts on the nociceptors of peripheral terminals through EP1, EP2, EP3, and EP4 receptors. Inhibition of PGE2 biosynthesis using NSAIDs and COX-2 inhibitors has emerged as the main class analgesics. Selective inhibition of PGE2 signaling down-stream of COX-2 may provide an opportunity to inhibit pronociceptive actions of PGE2 in endometriosis. DESIGN: Our working hypothesis is that pharmacological systemic blockade of EP2 and EP4 inhibits growth and innervations of endometriosis and peripheral and central nociceptive mechanisms. MATERIALS AND METHODS: Mixed population of human endometriotic epithelial cells (12Z-GFP) and stromal cells (22B-RFP) were xenografted into the peritoneal cavity Rag2g(c). On day 15 of xenograft, Group-1 (n¼6) mice were served as control. Group-2 (n¼6) mice were treated with EP2 and EP4 inhibitors. Group-3 (n¼6) were served as sham control. On day 30, motor activity of the experimental mice was examined by Digiscan. Then, the mice were euthanized and peritoneal endometriosis lesions were collected. RESULTS: A linear increase of 12Z-GFP or 22B-RFP cells was detected with the in vivo imager. Using a fluorescence stereo microscope, 18-20 lesions were detectable in the peritoneal cavity. Selective inhibition of EP2 and EP4 decreased growth of endometriosis about 50-60%, decreased expression of Protein Gene Product 9.5 (PGP 9.5), Substance P (SP), and Vesicular Monoamine Transporter (VMAT) in endometriosis innervations, and partially restored the motor activity in experimental endometriosis mice. CONCLUSION: These results together indicate that selective inhibition of EP2 and EP4 decreases growth of endometriosis, inhibits innervations of endometriosis and nociceptive pathways, and restores motor activity in endometriosis xenograft mice models. Supported by: 1R21HD066248-01A1 to JAA.
O-337 Wednesday, October 16, 2013 05:30 PM MULTIDETECTOR COMPUTERIZED TOMOGRAPHY ENTEROCLYSIS VERSUS MAGNETIC RESONANCE ENTEROCLYSIS IN THE DIAGNOSIS OF COLORECTAL ENDOMETRIOSIS. S. Ferrero,a U. Leone Roberti Maggiore,a P. L. Venturini,a G. A. Rollandi,b E. Biscaldi.b aDepartment of Obstetrics and Gynecology, San Martino Hospital and University of Genoa, Genoa, Liguria, Italy; bDepartment of Radiology, Galliera Hospital, Genoa, Liguria, Italy. OBJECTIVE: To compare the accuracy of multidetector computerized tomography enteroclysis (MDCT-e) and magnetic resonance enteroclysis
FERTILITY & STERILITYÒ
(MR-e) in determining the presence and the mucosa layer involvement of sigmoid and rectal endometriotic nodules. DESIGN: Single-center, prospective study. MATERIALS AND METHODS: Women with symptoms suggestive of bowel endometriosis underwent MDCT-e and MR-e. After retrograde colonic distension and injection of the intravenous contrast medium, patients were scanned on a 16-row MDCT scanner. MR-e was performed on a 1.5 T magnet using an 8 channels phased array coil; the intestinal distension was achieved by introducing in the rectum 250-300 ml of ultrasonographic gel diluted with saline solution. Radiological findings were compared with surgical and histological results. The McNemar’s test with the Yates continuity correction was used to compare the accuracy of the two techniques in the diagnosis of intestinal endometriosis. RESULTS: Two hundred and sixty patients were enrolled in the study; surgery demonstrated that 176 women (67.7%) had bowel endometriotic nodules. There was no difference in the accuracy of MDCT-e (98.5%) and MR-e (96.9%) in the diagnosis of sigmoid and rectal endometriosis (p ¼ 0.248). The sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio and negative likelihood ratio of MDCT-e and MR-e were respectively 98.3%, 98.8%, 99.4%, 96.5%, 81.59, 0.02 and 97.2%, 96.4%, 98.3%, 94.1%, 26.89, 0.03. MDCT-e accuracy had higher accuracy in determining the presence of endometriotic nodules infiltrating the mucosa layer compared with MR-e (p ¼ 0.041). CONCLUSION: Both MDCT-e and MR-e are accurate in the diagnosis of colorectal endometriosis. MDCT-e is more accurate than MR-e in determining correctly the depth of endometriotic nodule penetration in the intestinal wall.
O-338 Wednesday, October 16, 2013 05:45 PM INTERLEUKIN-1BETA INCREASES EXPRESSION OF TRYPTOPHAN 2,3-DIOXYGENASE AND STIMULATES TRYPTOPHAN METABOLISM IN ECTOPIC ENDOMETRIAL STROMAL CELLS. Y. Urata, Y. Osuga, K. Koga, Y. Hirota, T. Hirata, T. Fujii. Department of Obstetrics and Gynecology, University of Tokyo, Bunkyoku, Tokyo, Japan. OBJECTIVE: Tryptophan 2,3-dioxygenase (TDO) and indoleamine 2,3dioxygenase (IDO) are enzymes that catalyze the first and rate-limiting step of tryptophan degradation (i.e. from tryptophan to kynurenine) and thereby regulate tryptophan levels. Decrease in tryptophan levels inhibits T cell function and contributes to immune tolerance. While IFNg increases IDO expression, a molecule that regulates TDO expression remains to be elucidated. We evaluated the effect of interleukin (IL)-1b, a typical endometriosis-associated cytokine, on TDO expression in ectopic endometrial stromal cells (ESCs). DESIGN: Experimental study. MATERIALS AND METHODS: Under the approval of Institutional Review Board, ovarian endometriomas were obtained from women who had regular menstrual cycles and underwent laparoscopic surgery. ESCs were isolated from ovarian endometriomas. ESCs were treated with IL-1b for 5 hours to examine gene expression, for 24 hours to examine protein expression, and for 48 hours to examine the enzyme activity. Expression levels of TDO mRNA and IDO mRNA in ESCs were determined by quantitative real-time polymerase chain reaction. TDO protein was detected using western blotting. To study the enzyme activity of TDO and IDO, kynurenine concentration in the conditioned medium was measured. RESULTS: IL-1b (1 ng/ml) increased TDO mRNA expression to 6.3-fold of control but had no effect on IDO mRNA expression in ESCs. IL-1b (1 ng/ ml) increased TDO protein to 1.3-fold in ESCs and also increased kynurenine production to 1.9-fold in the conditioned medium. TDO siRNA suppressed the increase in IL-1b-induced kynurenine production. CONCLUSION: IL-1b increased TDO expression and stimulated tryptophan metabolism in ESCs. The IL-1b-induced increase in TDO expression may enhance immune tolerance to promote endometriosis. Supported by: Grants from the Ministry of Health, Labor, and Welfare and the Ministry of Education, Culture, Sports, Science, and Technology of Japan.
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