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Hormones and Inflammation: An Update on Endometriosis

  • Dora Pavone
  • Irene Turrini
  • Flavia Sorbi
  • Silvia Vannuccini
  • Tommaso Capezzuoli
  • Massimiliano Fambrini
  • Felice PetragliaEmail author
Chapter
Part of the ISGE Series book series (ISGE)

Abstract

Endometriosis is a complex inflammatory, hormone-dependent disease that affects up to 10% of women in reproductive age, causing pain and infertility. Although the pathogenesis of this disease remains unknown, in the most recent decades, there has been a substantial progress toward unraveling the enigma associated with this disorder. The present chapter focuses on the influence of hormonal, immunological, and inflammatory pathways in the pathogenesis of endometriosis. The disease is characterized by an increased estrogen activity, which stimulates both eutopic and ectopic endometrial tissue proliferation; in addition, an aberrant response to progesterone, named progesterone resistance, has been shown. Stress hormones are involved in endometriosis pathogenesis. In the present chapter, the relevance of several key points in the inflammatory dysregulation contributing to endometriosis onset and progression, and related symptoms, will also be discussed. Immunological factors (cytokines, chemokines, and prostaglandins) as well as cell-mediated mechanisms play a major role in endometriosis-associated pain. Aberrant hormonal and inflammatory pathways contribute also to inflammatory comorbidities and adverse pregnancy outcome.

Keywords

Endometriosis Estrogens Fibrosis Immune response Infertility Inflammation Neuroangiogenesis Pain Progesterone resistance Stress hormones 

References

  1. 1.
    Giudice LC. Endometriosis. N Engl J Med. 2010;362(25):2389–98.PubMedPubMedCentralCrossRefGoogle Scholar
  2. 2.
    De Ziegler D, Borghese B, Chapron C. Endometriosis and infertility: pathophysiology and management. Lancet. 2010;376:730–8.PubMedCrossRefPubMedCentralGoogle Scholar
  3. 3.
    Vercellini P, Viganò P, Somigliana E, Fedele L. Endometriosis: pathogenesis and treatment. Nat Rev Endocrinol. 2014;10(5):261–75.PubMedCrossRefGoogle Scholar
  4. 4.
    Zondervan KT, Becker CM, Koga K, Missmer SA, Taylor RN, Viganò P. Endometriosis. Nat Rev Dis Primers. 2018;4(1):9.PubMedCrossRefPubMedCentralGoogle Scholar
  5. 5.
    Fung JN, Montgomery GW. Genetics of endometriosis: state of the art on genetic risk factors for endometriosis. Best Pract Res Clin Obstet Gynaecol. 2018;50:61–71.PubMedCrossRefGoogle Scholar
  6. 6.
    Grimstad FW, Decherney A. A review of the epigenetic contributions to endometriosis. Clin Obstet Gynecol. 2017;60:467–76.PubMedCrossRefPubMedCentralGoogle Scholar
  7. 7.
    Patel BG, Rudnicki M, Yu J, Shu Y, Taylor RN. Progesterone resistance in endometriosis: origins, consequences and interventions. Acta Obstet Gynecol Scand. 2017;96:623–32.PubMedCrossRefGoogle Scholar
  8. 8.
    Han SJ, Jung SY, Wu SP, Hawkins SM, Park MJ, Kyo S, et al. Estrogen receptor β modulates apoptosis complexes and the inflammasome to drive the pathogenesis of endometriosis. Cell. 2015;163(4):960–74.PubMedPubMedCentralCrossRefGoogle Scholar
  9. 9.
    Riccio L d GC, Santulli P, Marcellin L, Abrão MS, Batteux F, Chapron C. Immunology of endometriosis. Best Pract Res Clin Obstet Gynaecol. 2018;50:39–49.PubMedCrossRefGoogle Scholar
  10. 10.
    Patel BG, Lenk EE, Lebovic DI, Shu Y, Yu J, Taylor RN. Pathogenesis of endometriosis: interaction between Endocrine and inflammatory pathways. Best Pract Res Clin Obstet Gynaecol. 2018;50:50–60.PubMedCrossRefPubMedCentralGoogle Scholar
  11. 11.
    Aznaurova Y, Zhumataev M, Roberts T, Aliper A, Zhavoronkov A. Molecular aspects of development and regulation of endometriosis. Reprod Biol Endocrinol. 2014;12(1):50.PubMedPubMedCentralCrossRefGoogle Scholar
  12. 12.
    Kitawaki J, Kado N, Ishihara H, Koshiba H, Kitaoka Y, Honjo H. Endometriosis: the pathophysiology as an estrogen-dependent disease. J Steroid Biochem Mol Biol. 2002;83:149–55.PubMedCrossRefPubMedCentralGoogle Scholar
  13. 13.
    Weiss G, Goldsmith LT, Taylor RN, Bellet D, Taylor HS. Inflammation in reproductive disorders. Reprod Sci. 2009;16:216–29.PubMedPubMedCentralCrossRefGoogle Scholar
  14. 14.
    Reis FM, Petraglia F, Taylor RN. Endometriosis: hormone regulation and clinical consequences of chemotaxis and apoptosis. Hum Reprod Update. 2013;19(4):406–18.PubMedPubMedCentralCrossRefGoogle Scholar
  15. 15.
    Amaral JD, Solá S, Steer CJ, Rodrigues CMP. Role of nuclear steroid receptors in apoptosis. Curr Med Chem. 2009;16(29):3886–902.PubMedCrossRefPubMedCentralGoogle Scholar
  16. 16.
    Luisi S, Galleri L, Marini F, Ambrosini G, Brandi ML, Petraglia F. Estrogen receptor gene polymorphisms are associated with recurrence of endometriosis. Fertil Steril. 2006;85(3):764–6.PubMedCrossRefPubMedCentralGoogle Scholar
  17. 17.
    Ferrero S, Remorgida V, Maganza C, Venturini PL, Salvatore S, Papaleo E, et al. Aromatase and endometriosis: estrogens play a role. Ann N Y Acad Sci. 2014;1317(1):17–23.PubMedCrossRefPubMedCentralGoogle Scholar
  18. 18.
    Bulun SE, Cheng YH, Yin P, Imir G, Utsunomiya H, Attar E, et al. Progesterone resistance in endometriosis: link to failure to metabolize estradiol. Mol Cell Endocrinol. 2006;248:94–103.PubMedCrossRefPubMedCentralGoogle Scholar
  19. 19.
    Bulun SE, Monsavais D, Pavone ME, Dyson M, Xue Q, Attar E, et al. Role of estrogen receptor-β in endometriosis. Semin Reprod Med. 2012;30(1):39–45.PubMedPubMedCentralCrossRefGoogle Scholar
  20. 20.
    Morsch DM, Carneiro MM, Lecke SB, Araújo FC, Camargos AF, Reis FM, et al. C-fos gene and protein expression in pelvic endometriosis: a local marker of estrogen action. J Mol Histol. 2009;40(1):53–8.PubMedCrossRefPubMedCentralGoogle Scholar
  21. 21.
    Cavallini A, Resta L, Caringella AM, Dinaro E, Lippolis C, Loverro G. Involvement of estrogen receptor-related receptors in human ovarian endometriosis. Fertil Steril. 2011;96(1):102–6.PubMedCrossRefPubMedCentralGoogle Scholar
  22. 22.
    Bulun SE, Monsavais D, Pavone ME, Dyson M, Xue Q, Attar E, et al. Role of estrogen receptor-beta in endometriosis. Semin Reprod Med. 2012;30(1):39–45.PubMedPubMedCentralCrossRefGoogle Scholar
  23. 23.
    Georgiou I, Syrrou M, Bouba I, Dalkalitsis N, Paschopoulos M, Navrozoglou I, et al. Association of estrogen receptor gene polymorphisms with endometriosis. Fertil Steril. 1999;72(1):164–6.PubMedCrossRefPubMedCentralGoogle Scholar
  24. 24.
    Lovely LP, Fazleabas AT, Fritz MA, McAdams DG, Lessey BA. Prevention of endometrial apoptosis: Randomized prospective comparison of human chorionic gonadotropin versus progesterone treatment in the luteal phase. J Clin Endocrinol Metab. 2005;90(4):2351–6.PubMedCrossRefPubMedCentralGoogle Scholar
  25. 25.
    Li HY, Chang SP, Yuan CC, Chao HT, Ng HT, Sung YJ. Nitric oxide induces extensive apoptosis in endometrial epithelial cells in the presence of progesterone: involvement of mitogen-activated protein kinase pathways. Mol Hum Reprod. 2001;7(8):755–63.PubMedCrossRefPubMedCentralGoogle Scholar
  26. 26.
    Tang L, Zhang Y, Pan H, Luo Q, Zhu X-M, Dong M-Y, et al. Involvement of cyclin B1 in progesterone-mediated cell growth inhibition, G2/M cell cycle arrest, and apoptosis in human endometrial cell. Reprod Biol Endocrinol. 2009;7:144.PubMedPubMedCentralCrossRefGoogle Scholar
  27. 27.
    Critchley HOD, Tong S, Cameron ST, Drudy TA, Kelly RW, Baird DT. Regulation of bcl-2 gene family members in human endometrium by antiprogestin administration in vivo. J Reprod Fertil. 1999;115:389–95.PubMedCrossRefPubMedCentralGoogle Scholar
  28. 28.
    Hayashi A, Tanabe A, Kawabe S, Hayashi M, Yuguchi H, Yamashita Y, et al. Dienogest increases the progesterone receptor isoform B/A ratio in patients with ovarian endometriosis. J Ovarian Res. 2012;5(1):31.PubMedPubMedCentralCrossRefGoogle Scholar
  29. 29.
    Patel B, Elguero S, Thakore S, Dahoud W, Bedaiwy M, Mesiano S. Role of nuclear progesterone receptor isoforms in uterine pathophysiology. Hum Reprod Update. 2015;21(2):155–73.PubMedCrossRefPubMedCentralGoogle Scholar
  30. 30.
    Attia GR, Zeitoun K, Edwards D, Johns A, Carr BR, Bulun SE. Progesterone receptor isoform A but not B is expressed in endometriosis. J Clin Endocrinol Metab. 2000;85(8):2897–902.PubMedGoogle Scholar
  31. 31.
    Burney RO, Talbi S, Hamilton AE, Kim CV, Nyegaard M, Nezhat CR, et al. Gene expression analysis of endometrium reveals progesterone resistance and candidate susceptibility genes in women with endometriosis. Endocrinology. 2007;148(8):3814–26.PubMedCrossRefGoogle Scholar
  32. 32.
    Al-Sabbagh M, Lam EWF, Brosens JJ. Mechanisms of endometrial progesterone resistance. Mol Cell Endocrinol. 2012;358:208–15.PubMedCrossRefGoogle Scholar
  33. 33.
    Pavone ME, Reierstad S, Sun H, Milad M, Bulun SE, Cheng YH. Altered retinoid uptake and action contributes to cell survival in endometriosis. J Clin Endocrinol Metab. 2010;95(11):E300–9.PubMedPubMedCentralCrossRefGoogle Scholar
  34. 34.
    Wieser F, Vigne JL, Ryan I, Hornung D, Djalali S, Taylor RN. Sulindac suppresses nuclear factor-kappaB activation and RANTES gene and protein expression in endometrial stromal cells from women with endometriosis. J Clin Endocrinol Metab. 2005;90(12):6441–7.PubMedCrossRefGoogle Scholar
  35. 35.
    Horie S, Harada T, Mitsunari M, Taniguchi F, Iwabe T, Terakawa N. Progesterone and progestational compounds attenuate tumor necrosis factor alpha-induced interleukin-8 production via nuclear factor kappa B inactivation in endometriotic stromal cells. Fertil Steril. 2005;83(5):1530–5.PubMedCrossRefGoogle Scholar
  36. 36.
    D’Amora P, Maciel TT, Tambellini R, Mori MA, Pesquero JB, Sato H, et al. Disrupted cell cycle control in cultured endometrial cells from patients with endometriosis harboring the progesterone receptor polymorphism PROGINS. Am J Pathol. 2009;175(1):215–24.PubMedPubMedCentralCrossRefGoogle Scholar
  37. 37.
    Wieser F, Schneeberger C, Tong D, Tempfer C, Huber JC, Wenzl R. PROGINS receptor gene polymorphism is associated with endometriosis. Fertil Steril. 2002;77(2):309–12.PubMedCrossRefGoogle Scholar
  38. 38.
    De Carvalho CV, Nogueira-de-Souza NC, Costa AMM, Baracat EC, Girão MJBC, D’amora P, et al. Genetic polymorphisms of cytochrome P450c17α (CYP17) and progesterone receptor genes (PROGINS) in the assessment of endometriosis risk. Gynecol Endocrinol. 2007;23(1):29–33.PubMedCrossRefGoogle Scholar
  39. 39.
    Tariverdian N, Siedentopf F, Rücke M, Blois SM, Klapp BF, Kentenich H, et al. Intraperitoneal immune cell status in infertile women with and without endometriosis. J Reprod Immunol. 2009;80(1–2):80–90.PubMedCrossRefGoogle Scholar
  40. 40.
    Tariverdian N, Rücke M, Szekeres-Bartho J, Blois SM, Karpf EF, Sedlmayr P, et al. Neuroendocrine circuitry and endometriosis: progesterone derivative dampens corticotropin-releasing hormone-induced inflammation by peritoneal cells in vitro. J Mol Med. 2010;88(3):267–78.PubMedCrossRefGoogle Scholar
  41. 41.
    Novembri R, Borges LE, Carrarelli P, Rocha ALL, De Pascalis F, Florio P, et al. Impaired CRH and urocortin expression and function in eutopic endometrium of women with endometriosis. J Clin Endocrinol Metab. 2011;96(4):1145–50.PubMedCrossRefGoogle Scholar
  42. 42.
    Florio P, Reis F, Torres P, Calonaci F, Toti P, Bocchi C, et al. Plasma urocortin levels in the diagnosis of ovarian endometriosis. Obstet Gynecol. 2007;110(3):594–600.PubMedCrossRefGoogle Scholar
  43. 43.
    Torricelli M, De Falco G, Florio P, Rossi M, Leucci E, Viganò P, et al. Secretory endometrium highly expresses urocortin messenger RNA and peptide: Possible role in the decidualization process. Hum Reprod. 2007;22(1):92–6.PubMedCrossRefGoogle Scholar
  44. 44.
    Florio P, Vale W, Petraglia F. Urocortins in human reproduction. Peptides. 2004;25:1751–7.PubMedCrossRefGoogle Scholar
  45. 45.
    Carrarelli P, Luddi A, Funghi L, Arcuri F, Batteux F, Dela Cruz C, et al. Urocortin and corticotrophin-releasing hormone receptor type 2 mRNA are highly expressed in deep infiltrating endometriotic lesions. Reprod Biomed Online. 2016;33(4):476–83.PubMedCrossRefGoogle Scholar
  46. 46.
    Khan KN, Kitajima M, Hiraki K, Fujishita A, Sekine I, Ishimaru T, et al. Immunopathogenesis of pelvic endometriosis: role of hepatocyte growth factor, macrophages and ovarian steroids. Am J Reprod Immunol. 2008;60:383–404.PubMedCrossRefGoogle Scholar
  47. 47.
    Jabbour HN, Kelly RW, Fraser HM, Critchley HOD. Endocrine regulation of menstruation. Endocr Rev. 2006;27:17–46.PubMedCrossRefGoogle Scholar
  48. 48.
    Zlotnik A, Yoshie O. The chemokine superfamily revisited. Immunity. 2012;36:705–12.PubMedPubMedCentralCrossRefGoogle Scholar
  49. 49.
    Galleri L, Luisi S, Rotondi M, Romagnani P, Cobellis L, Serio M, et al. Low serum and peritoneal fluid concentration of interferon-γ-induced protein-10 (CXCL10) in women with endometriosis. Fertil Steril. 2009;91(2):331–4.PubMedCrossRefGoogle Scholar
  50. 50.
    Agic A, Xu H, Rehbein M, Wolfler MM, Ebert AD, Hornung D. Cognate chemokine receptor 1 messenger ribonucleic acid expression in peripheral blood as a diagnostic test for endometriosis. Fertil Steril. 2007;87(4):982–4.PubMedCrossRefPubMedCentralGoogle Scholar
  51. 51.
    Yang Y, Zhang X, Zhou C, Huang X, Lin J, Xu H. Elevated immunoreactivity of RANTES and CCR1 correlate with the severity of stages and dysmenorrhea in women with deep infiltrating endometriosis. Acta Histochem. 2013;115(5):434–9.PubMedCrossRefPubMedCentralGoogle Scholar
  52. 52.
    Grandi G, Mueller MD, Papadia A, Kocbek V, Bersinger NA, Petraglia F, et al. Inflammation influences steroid hormone receptors targeted by progestins in endometrial stromal cells from women with endometriosis. J Reprod Immunol. 2016;117:30–8.PubMedCrossRefPubMedCentralGoogle Scholar
  53. 53.
    Hirata T, Osuga Y, Hamasaki K, Yoshino O, Ito M, Hasegawa A, et al. Interleukin (IL)-17A stimulates IL-8 secretion, cyclooxygensase-2 expression, and cell proliferation of endometriotic stromal cells. Endocrinology. 2008;149(3):1260–7.PubMedCrossRefPubMedCentralGoogle Scholar
  54. 54.
    Wu MH, Wang CA, Lin CC, Chen LC, Chang WC, Tsai SJ. Distinct regulation of cyclooxygenase-2 by interleukin-1β in normal and endometriotic stromal cells. J Clin Endocrinol Metab. 2005;90(1):286–95.PubMedCrossRefPubMedCentralGoogle Scholar
  55. 55.
    Tosti C, Pinzauti S, Santulli P, Chapron C, Petraglia F. Pathogenetic mechanisms of deep infiltrating endometriosis. Reprod Sci. 2015;22:1053–9.PubMedCrossRefPubMedCentralGoogle Scholar
  56. 56.
    Santulli P, Borghese B, Chouzenoux S, Vaiman D, Borderie D, Streuli I, et al. Serum and peritoneal interleukin-33 levels are elevated in deeply infiltrating endometriosis. Hum Reprod. 2012;27(7):2001–9.PubMedCrossRefPubMedCentralGoogle Scholar
  57. 57.
    Kang YJ, Jeung IC, Park A, Park YJ, Jung H, Kim TD, et al. An increased level of IL-6 suppresses NK cell activity in peritoneal fluid of patients with endometriosis via regulation of SHP-2 expression. Hum Reprod. 2014;29(10):2176–89.PubMedCrossRefPubMedCentralGoogle Scholar
  58. 58.
    Wu MH, Hsiao KY, Tsai SJ. Endometriosis and possible inflammation markers. Gynecol Minim Invasive Ther. 2015;4:61–7.CrossRefGoogle Scholar
  59. 59.
    Bullon P, Navarro JM. Inflammasome as a key pathogenic mechanism in endometriosis. Curr Drug Targets. 2017;18(9):997–1002.PubMedCrossRefPubMedCentralGoogle Scholar
  60. 60.
    Hassa H, Tanir HM, Tekin B, Kirilmaz SD, Sahin Mutlu F. Cytokine and immune cell levels in peritoneal fluid and peripheral blood of women with early- and late-staged endometriosis. Arch Gynecol Obstet. 2009;279(6):891–5.PubMedCrossRefPubMedCentralGoogle Scholar
  61. 61.
    Osuga Y, Koga K, Hirota Y, Hirata T, Yoshino O, Taketani Y. Lymphocytes in endometriosis. Am J Reprod Immunol. 2011;65:1–10.PubMedCrossRefPubMedCentralGoogle Scholar
  62. 62.
    Takamura M, Koga K, Izumi G, Hirata T, Harada M, Hirota Y, et al. Simultaneous detection and evaluation of four subsets of CD4+ T lymphocyte in lesions and peripheral blood in endometriosis. Am J Reprod Immunol. 2015;74(6):480–6.PubMedCrossRefPubMedCentralGoogle Scholar
  63. 63.
    Andreoli CG, Genro VK, Souza CA, Michelon T, Bilibio JP, Scheffel C, et al. T helper (Th)1, Th2, and Th17 interleukin pathways in infertile patients with minimal/mild endometriosis. Fertil Steril. 2011;95(8):2477–80.PubMedCrossRefPubMedCentralGoogle Scholar
  64. 64.
    Gogacz M, Gałczyński K, Wojtaś M, Winkler I, Adamiak A, Romanek-Piva K, et al. Fas-related apoptosis of peritoneal fluid macrophages in endometriosis patients: understanding the disease. J Immunol Res. 2017;2017:3175394.PubMedPubMedCentralCrossRefGoogle Scholar
  65. 65.
    Králíčková M, Fiala L, Losan P, Tomes P, Vetvicka V. Altered immunity in endometriosis: what came first? Immunol Investig. 2018;47(6):569–82.CrossRefGoogle Scholar
  66. 66.
    Allavena G, Carrarelli P, Del Bello B, Luisi S, Petraglia F, Maellaro E. Autophagy is upregulated in ovarian endometriosis: a possible interplay with p53 and heme oxygenase-1. Fertil Steril. 2015;103(5):1244–1251.e1.PubMedCrossRefPubMedCentralGoogle Scholar
  67. 67.
    Santulli P, Marcellin L, Noël JC, Borghese B, Fayt I, Vaiman D, et al. Sphingosine pathway deregulation in endometriotic tissues. Fertil Steril. 2012;97(4):904–11.PubMedCrossRefPubMedCentralGoogle Scholar
  68. 68.
    Burney RO, Giudice LC. Pathogenesis and pathophysiology of endometriosis. Fertil Steril. 2012;98:511–9.PubMedCrossRefPubMedCentralGoogle Scholar
  69. 69.
    Kobayashi H, Higashiura Y, Shigetomi H, Kajihara H. Pathogenesis of endometriosis: the role of initial infection and subsequent sterile inflammation (Review). Mol Med Rep. 2014;9(1):9–15.PubMedCrossRefPubMedCentralGoogle Scholar
  70. 70.
    Jiang C, Liu C, Guo J, Chen L, Luo N, Qu X, et al. The expression of Toll-like receptors in eutopic and ectopic endometrium and its implication in the inflammatory pathogenesis of adenomyosis. Sci Rep. 2017;7(1):7365.PubMedPubMedCentralCrossRefGoogle Scholar
  71. 71.
    Edwards RP, Huang X, Vlad AM. Chronic inflammation in endometriosis and endometriosis-associated ovarian cancer: new roles for the “old” complement pathway. Oncoimmunology. 2015;4(5):e1002732.PubMedPubMedCentralCrossRefGoogle Scholar
  72. 72.
    Sikora J, Wróblewska-Czech A, Smycz-Kubańska M, Mielczarek-Palacz A, Cygal A, Witek A, et al. The role of complement components C1q, MBL and C1 inhibitor in pathogenesis of endometriosis. Arch Gynecol Obstet. 2018;297(6):1495–501.PubMedPubMedCentralCrossRefGoogle Scholar
  73. 73.
    Lambeau G, Gelb MH. Biochemistry and physiology of mammalian secreted phospholipases A2. Annu Rev Biochem. 2008;77(1):495–520.PubMedCrossRefGoogle Scholar
  74. 74.
    McKinnon B, Bersinger NA, Wotzkow C, Mueller MD. Endometriosis-associated nerve fibers, peritoneal fluid cytokine concentrations, and pain in endometriotic lesions from different locations. Fertil Steril. 2012;97(2):373–80.PubMedCrossRefGoogle Scholar
  75. 75.
    Gori M, Luddi A, Belmonte G, Piomboni P, Tosti C, Funghi L, et al. Expression of microtubule associated protein 2 and synaptophysin in endometrium: high levels in deep infiltrating endometriosis lesions. Fertil Steril. 2016;105(2):435–43.PubMedCrossRefGoogle Scholar
  76. 76.
    Jess T, Frisch M, Jorgensen KT, Pedersen BV, Nielsen NM. Increased risk of inflammatory bowel disease in women with endometriosis: a nationwide Danish cohort study. Gut. 2012;61(9):1279–83.PubMedCrossRefGoogle Scholar
  77. 77.
    Alderman MH, Yoder N, Taylor HS. The systemic effects of endometriosis. Semin Reprod Med. 2017;35(3):263–70.PubMedCrossRefGoogle Scholar
  78. 78.
    Kvaskoff M, Mu F, Terry KL, Harris HR, Poole EM, Farland L, et al. Endometriosis: a high-risk population for major chronic diseases? Hum Reprod Update. 2015;21(4):500–16.PubMedPubMedCentralCrossRefGoogle Scholar
  79. 79.
    Pennell LM, Galligan CL, Fish EN. Sex affects immunity. J Autoimmun. 2012;38:J282–91.PubMedCrossRefGoogle Scholar
  80. 80.
    Falconer H, Mwenda JM, Chai DC, Wagner C, Song XY, Mihalyi A, et al. Treatment with anti-TNF monoclonal antibody (c5N) reduces the extent of induced endometriosis in the baboon. Hum Reprod. 2006;21(7):1856–62.PubMedCrossRefPubMedCentralGoogle Scholar
  81. 81.
    Nothnick WB. Treating endometriosis as an autoimmune disease. Fertil Steril. 2001;76:223–31.PubMedCrossRefPubMedCentralGoogle Scholar
  82. 82.
    Sundqvist J, Falconer H, Seddighzadeh M, Vodolazkaia A, Fassbender A, Kyama C, et al. Endometriosis and autoimmune disease: association of susceptibility to moderate/severe endometriosis with CCL21 and HLA-DRB1. Fertil Steril. 2011;95(1):437–40.PubMedCrossRefPubMedCentralGoogle Scholar
  83. 83.
    Bungum HF, Vestergaard C, Knudsen UB. Endometriosis and type 1 allergies/immediate type hypersensitivity: a systematic review. Eur J Obstet Gynecol Reprod Biol. 2014;179:209–15.PubMedCrossRefGoogle Scholar
  84. 84.
    Maggiore ULR, Ferrero S, Mangili G, Bergamini A, Inversetti A, Giorgione V, et al. A systematic review on endometriosis during pregnancy: diagnosis, misdiagnosis, complications and outcomes. Hum Reprod Update. 2016;22(1):70–103.CrossRefGoogle Scholar
  85. 85.
    Santulli P, Marcellin L, Menard S, Thubert T, Khoshnood B, Gayet V, et al. Increased rate of spontaneous miscarriages in endometriosis-affected women. Hum Reprod. 2016;31(5):1014–23.PubMedCrossRefGoogle Scholar
  86. 86.
    Zullo F, Spagnolo E, Saccone G, Acunzo M, Xodo S, Ceccaroni M, et al. Endometriosis and obstetrics complications: a systematic review and meta-analysis. Fertil Steril. 2017;108(4):667–672.e5.PubMedCrossRefGoogle Scholar
  87. 87.
    Vannuccini S, Clifton VL, Fraser IS, Taylor HS, Critchley H, Giudice LC, et al. Infertility and reproductive disorders: impact of hormonal and inflammatory mechanisms on pregnancy outcome. Hum Reprod Update. 2016;22(1):104–15.PubMedCrossRefGoogle Scholar
  88. 88.
    Pérez-López FR, Villagrasa-Boli P, Muñoz-Olarte M, Morera-Grau Á, Cruz-Andrés P, Hernandez AV. Association between endometriosis and preterm birth in women with spontaneous conception or using assisted reproductive technology: a systematic review and meta-analysis of cohort studies. Reprod Sci. 2018;25:311–9.PubMedCrossRefGoogle Scholar

Copyright information

© International Society of Gynecological Endocrinology 2019

Authors and Affiliations

  • Dora Pavone
    • 1
  • Irene Turrini
    • 1
  • Flavia Sorbi
    • 1
  • Silvia Vannuccini
    • 2
    • 3
  • Tommaso Capezzuoli
    • 1
  • Massimiliano Fambrini
    • 1
  • Felice Petraglia
    • 1
    Email author
  1. 1.Department of Biomedical, Experimental and Clinical Sciences “Mario Serio”Careggi University Hospital, University of FlorenceFlorenceItaly
  2. 2.Department of Health SciencesCareggi University Hospital, University of FlorenceFlorenceItaly
  3. 3.Department of Molecular and Developmental MedicineUniversity of SienaSienaItaly

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