{"paper_id":"6d1e75cf-af52-4d0d-84a5-a739d46d0bad","body_text":"BioMed Central\nPage 1 of 3\n(page number not for citation purposes)\nJournal of Ovarian Research\nOpen AccessBrief communication\nThrombospondin-1 serum levels do not correlate with pelvic pain in \npatients with ovarian endometriosis\nManuel García Manero*1, Begoña Olartecoechea1, Pedro Royo2 and \nJuan Luis Alcázar1\nAddress: 1Department of Obstetrics and Gynecology, Clínica Universitaria de Navarra, University of Navarra, Pamplona, Spain and 2Department \nof Obstetrics and Gynecology, Hospital San Jorge, Huesca, Spain\nEmail: Manuel García Manero* - mgmanero@unav.es; Begoña Olartecoechea - bolarteco@unav.es; Pedro Royo - proyo@alumni.unav.es; \nJuan Luis Alcázar - jlalcazar@unav.es\n* Corresponding author    \nAbstract\nObjetive: Thrombospondin-1 serum levels is correlate wi th pelvic pain in patients with ovarian\nendometriosis.\nPatients: Thrombospondin-1 serum levels were prospe ctively analysed in 51 patients (group A\nasymptomatic patients or patients presenting mild dysmenorrhea and women comprised group B\nsevere dysmenorrhea and/or chronic pelvic pain  and/or dyspareunia) who underwent surgery for\ncystic ovarian endometriosis to  asses whether a correlation exists among thrombospondin-1\nserum levels and pelvic pain.\nResults: From 56 patients, five cases were ultimateley excluded, because the histological diagnosis\nwas other than cystic ovarian endometriosis (2  teratomas and 3 haemor ragic cysts). The mean\nthrombospondin-1 serum levels in group A wa s 256,69 pg/ml_+37,07 and in group B was 291,41\npg/ml + 35,59.\nConclusion: Pain symptoms in ovarian endometriosis is not correlated wi th thrombospondin-1\nserum levels.\nIntroduction\nEndometriosis is a common gynaecologic disease of\nunknown aetiology. The most widely accepted hypothesis\nfor the development of endometriosis is retrograde men-\nstruation. However, some other factor renders certain\nwomen susceptible to the implantation and growth of this\nectopic endometrium.\nAngiogenesis appears as one of the processes involved in\nthe pathogenesis of endometriosis [1,2]. Angiogenic fac-\ntors are increased in the peritoneal fluid of patients with\nendometriosis [3,4] in peritoneal implants [5] and in\novarian endometriomas[6,7].\nOn the other hand some investigators have found that\nangiogenesis is related to pelvic pain [8]. We speculated\nthat ovarian endometriomas in patients presenting with\npelvic pain would have more angiogenesis than those in\nasymptomatic women and, therefore, their vascular fea-\ntures would be different [9]. Previosly, we studied ang-\niogenic factors (VEGF, IL-8) and their relationship with\npelvic pain and conclude that these angiogenic factors not\nPublished: 16 November 2009\nJournal of Ovarian Research 2009, 2:18 doi:10.1186/1757-2215-2-18\nReceived: 14 August 2009\nAccepted: 16 November 2009\nThis article is available from: http://www.ovarianresearch.com/content/2/1/18\n© 2009 Manero et al; licensee BioMed Central Ltd. \nThis is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), \nwhich permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.\n\nJournal of Ovarian Research 2009, 2:18 http://www.ovarianresea rch.com/content/2/1/18\nPage 2 of 3\n(page number not for citation purposes)\ncorrelate with pelvic pain in ovarian endometriosis [10-\n13].\nAngiogenesis is under the control of numerous inducers,\nincluding the vascular endothelial growth factor (VEGF)\nfamily and inhibitors, such as thrombospondin-1 (TSP-1)\n[9]\nThe aim of our study was to further investigate throm-\nbospondin-1 serum levels in asymptomatic patients and\nwomen with pelvic pain to determine whether this antian-\ngiogenic factor can be used as a serum marker of endome-\ntriosis activity.\nPatients\nMaterials and methods\nIn this prospective study 56 pre-menopausal women\n(mean age: 34.38 ± 7.07) were enrolled from February\n2003 to February 2005. Patients were divided in two\ngroups according to clinical complaints. Group A\nincluded asymptomatic patients or patients presenting\nmild or moderate dysmenorrhea, but without dispareunia\nor chronic pelvic pain (n = 25) Group B included patients\npresenting severe dysmenorrhea (with no response to\nconventional analgesic, treatment such as antiprostaglan-\ndins and requiring bed rest) and/or dyspareunia and/or\nchronic pelvic pain. (n = 26). The degree of pain was\nestablished using a visual analogue scale, VAS scale [14].\nAll patients provided informed consent after the nature of\nthe study was fully explained and Institutional Review\nBoard approval (Clinica Universitaria de Navarra) was\nobtained before starting the study.\nBlood samples were collected from all patients before\nanaesthesia by venipuncture into 10 cc sterile tubes and\nwere kept at room temperature until centrifugation at 400\n× g for 10 minutes. Less than 2 hours were allowed\nbetween blood collection and processing. Serum aliquots\nwere then frozen at -80°C until measurement of throm-\nbospondin-1 serum levels.\nSerum concentrations of thrombospondin-1 were meas-\nured with use of an immunoassay (Quantikine; R&D Sys-\ntems Inc., Minneapolis, MN). Thrombospondin-1\nconcentration can be measured in the range of 3.5 to\n2,000 pg/mL. Interassay and intra-assay coefficients of\nvariation were <10%.\nStatistical analysis\nStatistical analysis was performed using the SPSS version\n11.0 software (SPSS, Inc., Chicago IL). The mean serum\nlevel of thrombospondin-1 was compared in two groups\nusing the Student's t-test for independent samples.\nAll results of thrombospondin-1 expression were analysed\nby the Student's t-test. Spearman's correlation coefficient\nwas used to evaluate the relationship between parameters.\nStatistical significance was set at p < 0,05.\nResults\nFrom 56 patients, five cases were ultimateley excluded,\nbecause the histological diagnosis was other than cystic\novarian endometriosis (2 teratomas and 3 haemorragic\ncysts). The presence and type of pelvic adherences, mean\nrAFS score and stages, and sizes of endometriomas were\nnot statistically different between groups [15].\nThe mean thrombospondin-1 serum levels in group A was\n256,69 pg/ml_+37,07 and in group B was 291,41 pg/ml +\n35,59. In order to verify whether this observation could\nhave been biased by the lack of control for several possible\nconfounders, the mean thrombospondin-1 serum levels\nwas adjusted with respect to gravidity, length of menses,\ninfertility and BMI in a univariate general linear model\n[16]. Using this model, no significant difference was\nobserved in mean thrombospondin-1 serum levels\nbetween two groups.\nSerum thrombospondin-1 concentration did not correlate\nwith the diameter of the endometriomas and the severity\nof the endometriosis, assessed according to revised AFS\nscores.\nConclusion\nThe presence of ovarian cystic endometriosis is associated\nwith pelvic pain in women suffering this disease [8]. On\nthe other hand, angiogenic factors have been found\nincreased in ovarian endometriomas [6]. Angiogenesis is\nrelated to vascularization. Therefore, a correlation\nbetween vascularization and the presence of pelvic pain\nmight be assumed. Some studies assessing angiogenic\nactivity in endometriosis have used either morphometric\nor inmunohistochemical techniques in endometriotic tis-\nsue [6,17-19]. Other studies have evaluated vascular activ-\nity measuring serum [16,20] or peritoneal fluid\nconcentrations of angiogenic factors, such as VEGF [1,3].\nPreviously, some authors assessed that angiogenic factors\nare increased in the serum of patients with endometriosis\n[18] when compared with patients without endometrio-\nsis. Recently, Ohata has been demostrated that throm-\nbospondin-1 serum levels were higher in patients with\novarian endometrioma than in patients without endome-\ntriosis [21,22].\nPreviously, we demonstrated for the first time that IL-8\nand VEGF serum levels is not increased in patients diag-\nnosed of ovarian endometriomas who presenting pelvic\npain as compared with those who are asymptomatic.\nSome authors, have been demonstrated that expresion of\n\nPublish with BioMed Central   and  every \nscientist can read your work free of charge\n\"BioMed Central will be the most significant development for \ndisseminating the results of biomedical research in our lifetime.\"\nSir Paul Nurse, Cancer Research UK\nYour research papers will be:\navailable free of charge to the entire biomedical community\npeer reviewed and published immediately upon acceptance\ncited in PubMed and archived on PubMed Central \nyours — you keep the copyright\nSubmit your manuscript here:\nhttp://www.biomedcentral.com/info/publishing_adv.asp\nBioMedcentral\nJournal of Ovarian Research 2009, 2:18 http://www.ovarianresea rch.com/content/2/1/18\nPage 3 of 3\n(page number not for citation purposes)\nTSP-1 is higher in endometriotic lesions and is associated\nto the extent of their vascularization.\nIn the present study, we analysed if thrombospondin-1\nserum levels were correlated with ovarian endometrisosis\nand pelvic pain. We conclude that although throm-\nbospondin-1 seems to play a key role in the local develop-\nment of endometriotic lesions, the disease is not\nassociated with a significant modulation in the levels of\ncirculating thrombospondin-1 and the activity of\nendometriosis can not be monitored using serum levels.\nAlthough recently studies have demonstrated that IL-8\nand thrombospondin-1 serum level improve diagnostic\nreability of ovarian endometriosis we believe that the\noptimal serum marker should be used to monitoring the\nresponse of new antiangiogenic agents used in endometri-\nosis treatment.\nAbbreviations\npg/ml: picograms/mililiter; VEGF: Vascular Endothelium\nGrowth Factor; IL-8: Interleukin 8; TSP-1: Thrombospon-\ndin-1; VAS: Visual Analogic Scale; °C: Centrigrade\ndegrees; BMI: Body Mass Index; rAFS scores and stages:\nrevised American Fertility Society scores and stages.\nCompeting interests\nThe authors declare that they have no competing interests.\nAuthors' contributions\nMGM, designed the study and wrote the paper. BO and PR\nreviewed the literature related and corrected all areas in\nthe text including english language of the paper, covering\nthis fields. JLA was responsible for the methodological\nand statistics corrections.\nReferences\n1. Donnez J,  et al.: Vascular endothelial growth factor (VEGF) in\nendometriosis.  Hum Reprod 1998, 13:1686-1690.\n2. Matsuzaki S, Canis , Darcha C: Angiogenesis in endometriosis.\nGynecol Obstet Invest 1998, 46:111-115.\n3. McLaren J,  et al. : Vascular endothelial growth factor (VEGF)\nconcentrations are elevated in peritoneal fluid of women\nwith endometriosis.  Hum Reprod 1996, 11:220-223.\n4. Taylor RN, Lebovic DI, Mueller MD: Angiogenic factors in\nendometriosis.  Ann N Y Acad Sci 2002, 955:89-100.\n5. 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Matalliotakis IM,  et al.: Serum concentrations of growth factors\nin women with and without en dometriosis: the action of\nanti-endometriosis medicines.   Int Immunopharmacol  2003,\n3:81-89.\n21. Pellicer A,  et al. : The follicular and endo crine environment in\nwomen with endometriosis: local and systemic cytokine pro-\nduction.  Fertil Steril 1998, 70:425-431.\n22. Ohata Y, Harada T, Miyakoda H, Taniguchi F, Iwabe T, Terakawa N:\nSerum interleukin-8 levels are elevated in patients with\novarian endometrioma.  Fertil Steril 2008, 90:994-999.","source_license":"CC0","license_restricted":false}