Abstract
Objective: To compare serum levels of vascular endothelial growth factor (VEGF), tumor necrosis factor-alpha (TNF-α), and C-reactive protein (CRP) throughout the menstrual cycle in women with and without endometriosis and to quantify the association between these serum markers. Methods: Twenty five endometriosis patients (ASRM stage III–IV) and 13 controls were followed through one menstrual cycle. VEGF, TNF-α and CRP concentrations were measured with enzyme-linked immunosorbent assay in each of the four cycle phases (early and late proliferative and early and late secretory). Non-parametric methods and Pearson’s correlation coefficients were used for statistical analysis. Results: Increased serum levels of VEGF in secretory phases and of TNF-α in all cycle phases were observed. A positive correlation between CRP and VEGF was found in endometriosis patients but not in controls. Conclusions: Our results suggest that excessive systemic angiogenic activity is a feature of patients with endometriosis.
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References
American Society for Reproductive Medicine (1997) Revised American Society for Reproductive Medicine classification of endometriosis: 1996. Fertil Steril 67:817–821
Audebert A, Backstrom T, Barlow DH, Benagiano G, Brosens I, Buhler K, et’al (1992) Endometriosis 1991: a discussion document. Hum Reprod 7:432–435
Bedaiwy MA, Falcone T, Sharma RK, Goldberg JM, Attaran M, Nelson DR, et’al (2002) Prediction of endometriosis with serum and peritoneal fluid markers: a prospective controlled trial. Hum Reprod 17:426–431
Braun DP, Dmowski WP (1998) Endometriosis: abnormal endometrium and dysfunctional immune response. Curr Opin Obstet Gynecol 10:365–369
Darai E, Detchev R, Hugol D, Quang NT (2003) Serum and cyst fluid levels of interleukin (IL)-6, IL-8 and tumour necrosis factor-alpha in women with endometriomas and benign and malignant cystic ovarian tumours. Hum Reprod 18:1681–1685
Donnez J, Smoes P, Gillerot S, Casanas-Roux F, Nisolle M (1998) Vascular endothelial growth factor (VEGF) in endometriosis. Hum Reprod 13:1686–1690
Duleba AJ (1997) Diagnosis of endometriosis. Obstet Gynecol Clin North Am 24:331–345
Fasciani A, D’Ambrogio G, Bocci G, Luisi S, Artini PG, Genazzani AR (2001) Vascular endothelial growth factor and interleukin-8 in ovarian cystic pathology. Fertil Steril 75:1218–1221
Gagné D, Pagé M, Robitaille G, Hugo P, Gosselin D (2003) Levels of vascular endothelial growth factor (VEGF) in serum of patients with endometriosis. Hum Reprod 18:1674–1680
Harada T, Iwabe T, Terakawa N (2001) Role of cytokines in endometriosis. Fertil Steril 76:1–10
Healy DL, Rogers PA, Hii L, Wingfield M (1998) Angiogenesis: a new theory for endometriosis. Hum Reprod Update 4:736–740
Iwabe T, Harada T, Tsudo T, Nagano Y, Tanikawa M, Terakawa N (2000) Tumor necrosis factor-α promotes proliferation of the endometriotic stromal cells by inducing interleukin-8 gene and protein expression. J Clin Endocrinol Metab 85:824–829
Ladoux A, Frelin C (1993) Hypoxia is a strong inducer of vascular endothelial growth factor mRNA expression in the heart. Biochem Biophys Res Commun 195:1005–1010
Matalliotakis I, Neonaki M, Zolindaki A, Hassan E, Georgoulias V, Koumantakis E (1997) Changes in immunologic variables (TNF-α, sCD8 and sCD4) during danazol treatment in patients with endometriosis. Int J Fertil Womens Med 42:211–214
Matalliotakis IM, Goumenou AG, Koumantakis GE, Neonaki MA, Koumantakis EE,Dionyssopoulou E (2003) Serum concentrations of growth factors in women with and without endometriosis: the action of anti-endometriosis medicines. Int Immunopharmacol 3:81–89
Matarese G, Alviggi C, Sanna V, Howard JK, Lord GM, Carravetta C, et’al (2000) Increased leptin levels in serum and peritoneal fluid of patients with pelvic endoemtriosis. J Clin Endocrinol Metab 85:2483–2487
Missmer SA, Cramer DW (2003) The epidemiology of endometriosis. Obstet Gynecol Clin N Am 30:1–19
Packard CJ, O’Reilly DSJ, Caslake MJ, McMahon AD, Ford I, Cooney J, et’al (2000) Lipoprotein-associated phospholipase A2 as an independent predictor of coronary heart disease. West of Scotland Coronary Prevention Study Group. N Engl J Med 343:1148–1155
Pellicer A, Albert C, Mercader A, Bonilla-Musoles F, Remohi J, Simón C (1998) The follicular and endocrine environment in women with endometriosis: local and systemic cytokine production. Fertil Steril 70:425–431
Seli E, Berkkanoglu M, Arici A (2003) Pathogenesis of endometriosis. Obstet Gynecol Clin N Am 30:41–61
Shifren JL, Tseng JF, Zaloudek CJ, Ryan IP, Meng YG, Ferrara N, et’al (1996) Ovarian steroid regulation of vascular endothelial growth factor in the human endometrium: implications for angiogenesis during the menstrual cycle and in the pathogenesis of endometriosis. J Clin Endocrinol Metab 81:3112–3118
Steff AM, Gagne D, Page M, Rioux A, Hugo P, Gosselin D (2004) Serum concentrations of insulin-like growth factor-1, soluble tumor necrosis factor receptor-1 and angiogenin in endometriosis patients. Am J Reprod Immunol 51:166–173
Vinatier D, Dufour P, Oosterlynck D (1996) Immunological aspects of endometriosis. Hum Reprod Update 2:371–384
Vercellini P, Trespidi L, De Giorgi O, Cortesi I, Parazzini F, Crosignani PG (1996) Endometriosis and pelvic pain: relation to disease stage and localization. Fertil Steril 65:299–304
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Xavier, P., Belo, L., Beires, J. et al. Serum levels of VEGF and TNF-α and their association with C-reactive protein in patients with endometriosis. Arch Gynecol Obstet 273, 227–231 (2006). https://doi.org/10.1007/s00404-005-0080-4
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DOI: https://doi.org/10.1007/s00404-005-0080-4