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Environmental factors and hormones in the development of rheumatoid arthritis

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Abstract

The etiopathogenesis of rheumatoid arthritis (RA) is partially understood. Genetic, environmental, and hormonal factors and their interactions are considered to play an important role on disease development. The relative contribution of environmental factors to RA development is probably larger than previously thought. The aim of this review is to appraise robust evidence about the role of environmental and hormonal risk factors for RA. We will discuss inhaled pollutants, nutritional habits, infectious, hormonal, and reproductive factors. As some of these factors are potentially modifiable, understanding their impact on RA development opens new opportunities for potential interventions and disease prevention.

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References

  1. Furer V, Greenberg JD, Attur M, Abramson SB, Pillinger MH (2010) The role of microRNA in rheumatoid arthritis and other autoimmune diseases. Clin Immunol 136(1):1–15

    Article  CAS  PubMed  Google Scholar 

  2. Klareskog L, Stolt P, Lundberg K et al (2006) A new model for an etiology of rheumatoid arthritis: smoking may trigger HLA-DR (shared epitope)-restricted immune reactions to autoantigens modified by citrullination. Arthritis Rheum 54(1):38–46

    Article  CAS  PubMed  Google Scholar 

  3. Mankia K, Emery P (2016) Preclinical rheumatoid arthritis: progress toward prevention. Arthritis Rheumatol. 68(4):779–788

    Article  PubMed  Google Scholar 

  4. Silman AJ, Hennessy E, Ollier B (1992) Incidence of rheumatoid arthritis in a genetically predisposed population. Br J Rheumatol 31(6):365–368

    Article  CAS  PubMed  Google Scholar 

  5. Frisell T, Holmqvist M, Kallberg H et al (2013) Familial risks and heritability of rheumatoid arthritis: role of rheumatoid factor/anti-citrullinated protein antibody status, number and type of affected relatives, sex, and age. Arthritis Rheum 65(11):2773–2782

    Article  CAS  PubMed  Google Scholar 

  6. Sparks JA, Chen CY, Hiraki LT et al (2014) Contributions of familial rheumatoid arthritis or lupus and environmental factors to risk of rheumatoid arthritis in women: a prospective cohort study. Arthritis Care Res (Hoboken). 66(10):1438–1446

    Article  PubMed  PubMed Central  Google Scholar 

  7. Karlson EW, Watts J, Signorovitch J et al (2007) Effect of glutathione S-transferase polymorphisms and proximity to hazardous waste sites on time to systemic lupus erythematosus diagnosis: results from the Roxbury lupus project. Arthritis Rheum 56(1):244–254

    Article  CAS  PubMed  Google Scholar 

  8. Kallberg H, Padyukov L, Plenge RM et al (2007) Gene-gene and gene-environment interactions involving HLA-DRB1, PTPN22, and smoking in two subsets of rheumatoid arthritis. Am J Hum Genet 80(5):867–875

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  9. Costenbader KH, Karlson EW (2006) Epstein-Barr virus and rheumatoid arthritis: is there a link? Arthritis Res Ther. 8(1):204

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  10. Hart JE, Laden F, Puett RC, Costenbader KH, Karlson EW (2009) Exposure to traffic pollution and increased risk of rheumatoid arthritis. Environ Health Perspect 117(7):1065–1069

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Lu B, Solomon DH, Costenbader KH et al (2010) Alcohol consumption and markers of inflammation in women with preclinical rheumatoid arthritis. Arthritis Rheum 62(12):3554–3559

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Kallberg H, Jacobsen S, Bengtsson C et al (2009) Alcohol consumption is associated with decreased risk of rheumatoid arthritis: results from two Scandinavian case-control studies. Ann Rheum Dis 68(2):222–227

    Article  CAS  PubMed  Google Scholar 

  13. Karlson EW, Mandl LA, Hankinson SE, Grodstein F (2004) Do breast-feeding and other reproductive factors influence future risk of rheumatoid arthritis? Results from the Nurses’ Health Study. Arthritis Rheum 50(11):3458–3467

    Article  PubMed  Google Scholar 

  14. Sugiyama D, Nishimura K, Tamaki K et al (2010) Impact of smoking as a risk factor for developing rheumatoid arthritis: a meta-analysis of observational studies. Ann Rheum Dis 69(1):70–81

    Article  CAS  PubMed  Google Scholar 

  15. Jiang X, Alfredsson L, Klareskog L, Bengtsson C (2014) Smokeless tobacco (moist snuff) use and the risk of developing rheumatoid arthritis: results from a case-control study. Arthritis Care Res (Hoboken) 66(10):1582–1586

    Article  Google Scholar 

  16. Demoruelle MK, Weisman M, Simonian P (2011) Airways abnormalities and rheumatoid arthritis-related autoantibodies in subjects without arthritis: early injury or initiating site of autoimmunity? Arthritis Rheum 64:1756–1761

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  17. Hill JA, Bell DA, Brintnell W et al (2008) Arthritis induced by posttranslationally modified (citrullinated) fibrinogen in DR4-IE transgenic mice. J Exp Med 205(4):967–979

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Lundström E, Hartshorne T, Li K et al (2011) Effects of GSTM1 in rheumatoid arthritis; results from the Swedish EIRA study. PLoS One 6(3):e17880

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  19. Criswell LA, Saag KG, Mikuls TR, et al. Smoking interacts with genetic risk factors in the development of rheumatoid arthritis among older Caucasian women. Ann Rheum Dis. 2006

  20. Mikuls T, LeVan T, Gould K et al (2012) Impact of interactions of cigarette smoking with NAT2 polymorphisms on rheumatoid arthritis risk in African Americans. Arthr Rheum 64(3):655–664

    Article  CAS  Google Scholar 

  21. De Roos A, Koehoorn M, Tamburic L, Davies H, Brauer M (2014) Proximity to traffic, ambient air pollution, and community noise in relation to incident rheumatoid arthritis. Environ Health Perspect 122(10):1075–1080

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Chang K, Hsu C, Muo C et al (2016) Air pollution exposure increases the risk of rheumatoid arthritis: a longitudinal and nationwide study. Environ Int 94:495–499

    Article  CAS  PubMed  Google Scholar 

  23. Hart J, Källberg H, Laden F et al (2013) Ambient air pollution exposures and risk of rheumatoid arthritis: results from the Swedish EIRA case-control study. Ann Rheum Dis 72(6):888–894

    Article  CAS  PubMed  Google Scholar 

  24. Farhata SCL, Silva CA, Orione M et al (2011) Air pollution in autoimmune rheumatic diseases: a review. Autoimmun Rev 11(1):14–21

    Article  CAS  Google Scholar 

  25. Caplan A (1953) Certain unusual radiological appearances in the chest of coal-miners suffering from rheumatoid arthritis. Thorax 8:29–35

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Sluis-Cremer G, Hessel P, Hnizdo E, Churchill A (1986) Relationship between silicosis and rheumatoid arthritis. Thorax 41:596–601

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Klockars M, Koskela R, Jarvinen E, Kolari P, Rossi A (1987) Silica exposure and rheumatoid arthritis: a follow up study of granite workers 1940–81. Br Med J (Clin Res Ed) 294:997–1000

    Article  CAS  Google Scholar 

  28. Blanc P, Järvholm B, Toren K (2015) Prospective risk of rheumatologic disease associated with occupational exposure in a cohort of male construction workers. Am J Med 128(10):1094–1101

    Article  PubMed  Google Scholar 

  29. Turner S, Cherry N (2000) Rheumatoid arthritis in workers exposed to silica in the pottery industry. Occup Environ Med 57:443–447

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Stolt P, Yahya A, Bengtsson C et al (2010) Silica exposure among male current smokers is associated with a high risk of developing ACPA-positive rheumatoid arthritis. Ann Rheum Dis 69(6):1072–1076

    Article  CAS  PubMed  Google Scholar 

  31. Yahya A, Bengtsson C, Larsson P, et al (2014) Silica exposure is associated with an increased risk of developing ACPA-positive rheumatoid arthritis in an Asian population: evidence from the Malaysian MyEIRA case-control study. Mod Rheumatol.24(2)

  32. Pollard K (2016) Silica, silicosis, and autoimmunity. Front Immunol 7:97

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  33. Too C, Muhamad N, Lar A et al (2016) Occupational exposure to textile dust increases the risk of rheumatoid arthritis: results from a Malaysian population-based case-control study. Ann Rheum Dis 75(6):997–1002

    Article  CAS  PubMed  Google Scholar 

  34. Meyer A, Sandler D, Beane-Freeman L, Hoffman J, Parks C, editors (2016) Pesticide exposure and risk of rheumatoid arthritis in licensed male pesticide applicators in the Agricultural Health Study [abstract]. ACR annual scientific conference. Washington, DC: Arthritis Rheumatol

  35. Parks C, Hoppin J, De Roos A et al (2016) Rheumatoid arthritis in agricultural health study spouses: associations with pesticides and other farm exposures. Environ Health Perspect 124:1728–1734

    PubMed  PubMed Central  Google Scholar 

  36. Jonsson IM, Verdrengh M, Brisslert M et al (2007) Ethanol prevents development of destructive arthritis. Proc Natl Acad Sci U S A 104(1):258–263

    Article  CAS  PubMed  Google Scholar 

  37. Scott I, Tan R, Stahl D et al (2013) The protective effect of alcohol on developing rheumatoid arthritis: a systematic review and meta-analysis. Rheumatology (Oxford) 52(5):856–867

    Article  CAS  Google Scholar 

  38. Nissen MJ, Gabay C, Scherer A, Finckh A (2010) The effect of alcohol on radiographic progression in rheumatoid arthritis. Arthritis Rheum 62(5):1265–1272

    Article  CAS  PubMed  Google Scholar 

  39. Gan R, Young K, Zerbe G et al (2016) Lower omega-3 fatty acids are associated with the presence of anti-cyclic citrullinated peptide autoantibodies in a population at risk for future rheumatoid arthritis: a nested case-control study. Rheumatology (Oxford) 55(2):367–376

    Article  Google Scholar 

  40. Di Giuseppe D, Wallin A, Bottai M, Askling J, Wolk A (2014) Long-term intake of dietary long-chain n-3 polyunsaturated fatty acids and risk of rheumatoid arthritis: a prospective cohort study of women. Ann Rheum Dis 73(11):1949–1953

    Article  CAS  PubMed  Google Scholar 

  41. Di Giuseppe D, Crippa A, Orsini N, Wolk A (2014) Fish consumption and risk of rheumatoid arthritis: a dose-response meta-analysis. Arthritis Res Ther. 16(5):446

    Article  PubMed  PubMed Central  Google Scholar 

  42. Proudman SM, James MJ, Spargo LD, Metcalf RG, Sullivan TR, Rischmueller M, Flabouris K, Wechalekar MD, Lee AT, Cleland LG (2015) Fish oil in recent onset rheumatoid arthritis: a randomised, double-blind controlled trial within algorithm-based drug use. Ann Rheum Dis 74(1):89–95

    Article  CAS  PubMed  Google Scholar 

  43. Sundström B, Johansson I, Rantapää DS (2015) Interaction between dietary sodium and smoking increases the risk for rheumatoid arthritis: results from a nested case-control study. Rheumatology (Oxford) 54(3):487–493

    Article  Google Scholar 

  44. Hu Y, Costenbader KH, Gao X et al (2014) Sugar-sweetened soda consumption and risk of developing rheumatoid arthritis in women. Am J Clin Nutr 100(3):959–967

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Finckh A, Turesson C (2014) Impact of obesity in rheumatoid arthritis. Ann Rheum Dis. (in press)

  46. Lu B, Hiraki L, Sparks JA, et al (2014) Being overweight or obese and risk of developing rheumatoid arthritis among women: a prospective cohort study. Ann Rheum Dis

  47. Wesley A, Bengtsson C, Elkan AC et al (2013) Association between body mass index and anti-citrullinated protein antibody-positive and anti-citrullinated protein antibody-negative rheumatoid arthritis: results from a population-based case-control study. Arthritis Care Res (Hoboken) 65(1):107–112

    Article  Google Scholar 

  48. Turesson C, Bergström U, Pikwer M, Nilsson J, Jacobsson L (2016) A high body mass index is associated with reduced risk of rheumatoid arthritis in men, but not in women. Rheumatology (Oxford) 55(2):307–314

    Article  Google Scholar 

  49. Caliskan R, Masatlioglu S, Aslan M et al (2005) The relationship between arthritis and human parvovirus B19 infection. Rheumatol Int 26(1):7–11

    Article  CAS  PubMed  Google Scholar 

  50. Sepulveda-Delgado J, Vera-Lastra OL, Trujillo-Murillo K et al (2016) Inflammatory biomarkers, disease activity index, and self-reported disability may be predictors of chronic arthritis after chikungunya infection: brief report. Clin Rheumatol. doi:10.1007/s10067-016-3419-2

    PubMed  Google Scholar 

  51. Bouquillard E, Combe B (2009) Rheumatoid arthritis after chikungunya fever: a prospective follow-up study of 21 cases. Ann Rheum Dis 68(9):1505–1506

    Article  CAS  PubMed  Google Scholar 

  52. Su FH, Wu CS, Sung FC et al (2014) Chronic hepatitis C virus infection is associated with the development of rheumatoid arthritis: a nationwide population-based study in Taiwan. PLoS One 9(11):e113579

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  53. Liu FC, Chao YC, Hou TY et al (2008) Usefulness of anti-CCP antibodies in patients with hepatitis C virus infection with or without arthritis, rheumatoid factor, or cryoglobulinemia. Clin Rheumatol 27(4):463–467

    Article  PubMed  Google Scholar 

  54. Hsieh YF, Liu HW, Hsu TC et al (2007) Serum reactivity against Borrelia burgdorferi OspA in patients with rheumatoid arthritis. Clin Vaccine Immunol 14(11):1437–1441

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Arvikar SL, Crowley JT, Sulka KB, Steere AC (2017) Autoimmune arthritides, rheumatoid arthritis, psoriatic arthritis, or peripheral spondyloarthritis following Lyme disease. Arthritis Rheumatol. 69(1):194–202

    Article  CAS  PubMed  Google Scholar 

  56. Sandberg ME, Bengtsson C, Klareskog L, Alfredsson L, Saevarsdottir S (2015) Recent infections are associated with decreased risk of rheumatoid arthritis: a population-based case-control study. Ann Rheum Dis 74(5):904–907

    Article  PubMed  Google Scholar 

  57. de Pablo P, Dietrich T, McAlindon TE (2008) Association of periodontal disease and tooth loss with rheumatoid arthritis in the US population. J Rheumatol 35(1):70–76

    PubMed  Google Scholar 

  58. de Pablo P, Chapple ILC, Buckley CD, Dietrich T (2009) Periodontitis in the systemic rheumatic diseases. Nat Rev Rheumatol 5:218–224

    Article  PubMed  Google Scholar 

  59. Demmer RT, Molitor JA, Jacobs DR Jr, Michalowicz BS (2011) Periodontal disease, tooth loss and incident rheumatoid arthritis: results from the First National Health and Nutrition Examination Survey and its epidemiological follow-up study. J Clin Periodontol 38(11):998–1006

    Article  PubMed  PubMed Central  Google Scholar 

  60. McGraw WT, Potempa J, Farley D, Travis J (1999) Purification, characterization, and sequence analysis of a potential virulence factor from Porphyromonas gingivalis, peptidylarginine deiminase. Infect Immun 67(7):3248–3256

    CAS  PubMed  PubMed Central  Google Scholar 

  61. Janssen KM, Vissink A, de Smit MJ, Westra J, Brouwer E (2013) Lessons to be learned from periodontitis. Curr Opin Rheumatol 25(2):241–247

    Article  PubMed  Google Scholar 

  62. Nesse W, Westra J, van der Wal JE et al (2012) The periodontium of periodontitis patients contains citrullinated proteins which may play a role in ACPA (anti-citrullinated protein antibody) formation. J Clin Periodontol 39(7):599–607

    Article  CAS  PubMed  Google Scholar 

  63. Goh CE, Kopp J, Papapanou PN, Molitor JA, Demmer RT (2016) Association between serum antibodies to periodontal bacteria and rheumatoid factor in the Third National Health and Nutrition Examination Survey. Arthritis Rheumatol. 68(10):2384–2393

    Article  CAS  PubMed  Google Scholar 

  64. Kharlamova N, Jiang X, Sherina N et al (2016) Antibodies to Porphyromonas gingivalis indicate interaction between oral infection, smoking, and risk genes in rheumatoid arthritis etiology. Arthritis Rheumatol 68(3):604–613

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Fisher BA, Cartwright AJ, Quirke AM et al (2015) Smoking, Porphyromonas gingivalis and the immune response to citrullinated autoantigens before the clinical onset of rheumatoid arthritis in a Southern European nested case-control study. BMC Musculoskelet Disord 16:331

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  66. Konig MF, Abusleme L, Reinholdt J et al (2016) Aggregatibacter actinomycetemcomitans-induced hypercitrullination links periodontal infection to autoimmunity in rheumatoid arthritis. Sci Transl Med 8(369):369ra176

    Article  PubMed  Google Scholar 

  67. da Silva AP, Bissada NF (2016) Arthritis and periodontitis: an association debated for over two centuries. Curr Rheumatol Rev 12(3):202–207

    Article  PubMed  Google Scholar 

  68. McLean MH, Dieguez D Jr, Miller LM, Young HA (2015) Does the microbiota play a role in the pathogenesis of autoimmune diseases? Gut 64(2):332–341

    Article  CAS  PubMed  Google Scholar 

  69. Erickson AR, Cantarel BL, Lamendella R et al (2012) Integrated metagenomics/metaproteomics reveals human host-microbiota signatures of Crohn’s disease. PLoS One 7(11):e49138

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Vaahtovuo J, Munukka E, Korkeamaki M, Luukkainen R, Toivanen P (2008) Fecal microbiota in early rheumatoid arthritis. J Rheumatol 35(8):1500–1505

    CAS  PubMed  Google Scholar 

  71. Zhang X, Zhang D, Jia H et al (2015) The oral and gut microbiomes are perturbed in rheumatoid arthritis and partly normalized after treatment. Nat Med 21(8):895–905

    Article  CAS  PubMed  Google Scholar 

  72. Scher JU, Sczesnak A, Longman RS et al (2013) Expansion of intestinal Prevotella copri correlates with enhanced susceptibility to arthritis. Elife 2:e01202

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  73. Pianta A, Arvikar S, Strle K et al (2016) Evidence for immune relevance of Prevotella copri, a gut microbe, in patients with rheumatoid arthritis. Arthritis Rheumatol. doi:10.1002/art.40003

    Google Scholar 

  74. Gomez A, Luckey D, Yeoman CJ et al (2012) Loss of sex and age driven differences in the gut microbiome characterize arthritis-susceptible 0401 mice but not arthritis-resistant 0402 mice. PLoS One 7(4):e36095

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. de Hair MJ, Lehmann KA, van de Sande MG et al (2012) The clinical picture of rheumatoid arthritis according to the 2010 American College of Rheumatology/European League Against Rheumatism criteria: is this still the same disease? Arthritis Rheum 64(2):389–393

    Article  PubMed  Google Scholar 

  76. Kvien TK, Uhlig T, Odegard S, Heiberg MS (2006) Epidemiological aspects of rheumatoid arthritis: the sex ratio. Ann N Y Acad Sci 1069:212–222

    Article  PubMed  Google Scholar 

  77. Kovacs WJ, Olsen NJ (2011) Sexual dimorphism of RA manifestations: genes, hormones and behavior. Nat Rev Rheumatol 7(5):307–310

    Article  CAS  PubMed  Google Scholar 

  78. Hughes GC, Choubey D (2014) Modulation of autoimmune rheumatic diseases by oestrogen and progesterone. Nat Rev Rheumatol 10(12):740–751

    Article  CAS  PubMed  Google Scholar 

  79. Frisell T, Saevarsdottir S, Askling J (2016) Family history of rheumatoid arthritis: an old concept with new developments. Nat Rev Rheumatol 12(6):335–343

    Article  CAS  PubMed  Google Scholar 

  80. Straub RH (2007) The complex role of estrogens in inflammation. Endocr Rev 28(5):521–574

    Article  CAS  PubMed  Google Scholar 

  81. Bengtsson CMS, Sparks JA, Costenbader KH, Karlson EW (2014) Post-menopausal factors and the risk of seropositive and seronegative rheumatoid arthritis phenotypes: results from the Nurses’ Health Study. Arthritis and Rheumatology 66(11 (supplement)):S1261

    Google Scholar 

  82. Beydoun HA, el-Amin R, McNeal M, Perry C, Archer DF (2013) Reproductive history and postmenopausal rheumatoid arthritis among women 60 years or older: Third National Health and Nutrition Examination Survey. Menopause 20(9):930–935

    Article  PubMed  Google Scholar 

  83. Pikwer M, Bergstrom U, Nilsson JA, Jacobsson L, Turesson C (2012) Early menopause is an independent predictor of rheumatoid arthritis. Ann Rheum Dis 71(3):378–381

    Article  PubMed  Google Scholar 

  84. Chen JY, Ballou SP (2015) The effect of antiestrogen agents on risk of autoimmune disorders in patients with breast cancer. J Rheumatol 42(1):55–59

    Article  PubMed  CAS  Google Scholar 

  85. Pedersen M, Jacobsen S, Klarlund M et al (2006) Environmental risk factors differ between rheumatoid arthritis with and without auto-antibodies against cyclic citrullinated peptides. Arthritis Res Ther. 8(4):R133

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  86. Pedersen M, Jacobsen S, Garred P et al (2007) Strong combined gene-environment effects in anti-cyclic citrullinated peptide-positive rheumatoid arthritis: a nationwide case-control study in Denmark. Arthritis Rheum 56(5):1446–1453

    Article  PubMed  Google Scholar 

  87. Chen Q, Jin Z, Xiang C et al (2014) Absence of protective effect of oral contraceptive use on the development of rheumatoid arthritis: a meta-analysis of observational studies. Int J Rheum Dis 17(7):725–737

    Article  PubMed  Google Scholar 

  88. Pladevall-Vila M, Delclos GL, Varas C et al (1996) Controversy of oral contraceptives and risk of rheumatoid arthritis: meta-analysis of conflicting studies and review of conflicting meta-analyses with special emphasis on analysis of heterogeneity. Am J Epidemiol 144(1):1–14

    Article  CAS  PubMed  Google Scholar 

  89. Alpizar-Rodriguez D, Pluchino N, Canny G, Gabay C, Finckh A (2016) The role of female hormonal factors in the development of rheumatoid arthritis. Rheumatology (Oxford). doi:10.1093/rheumatology/kew318

    Google Scholar 

  90. Berglin E, Kokkonen H, Einarsdottir E, Agren A, Rantapaa DS (2010) Influence of female hormonal factors, in relation to autoantibodies and genetic markers, on the development of rheumatoid arthritis in northern Sweden: a case-control study. Scand J Rheumatol 39(6):454–460

    Article  CAS  PubMed  Google Scholar 

  91. Orellana CKL, Alfredsson, L Bengtsson, C (2015) Breastfeeding, oral contraceptive and the risk of rheumatoid arthritis: results from the Swedish Epidemiological Investigation of RA Study [abstract]. Arthritis Rheumatol 67(supp 10)

  92. Orellana C, Saevarsdottir S, Klareskog L et al (2015) Postmenopausal hormone therapy and the risk of rheumatoid arthritis: results from the Swedish EIRA population-based case-control study. Eur J Epidemiol. doi:10.1007/s10654-015-0004-y

    PubMed  PubMed Central  Google Scholar 

  93. Peschken CA, Robinson DB, Hitchon CA et al (2012) Pregnancy and the risk of rheumatoid arthritis in a highly predisposed north American native population. J Rheumatol 39(12):2253–2260

    Article  PubMed  Google Scholar 

  94. Silman A, Kay A, Brennan P (1992) Timing of pregnancy in relation to the onset of rheumatoid arthritis. Arthritis Rheum 35(2):152–155

    Article  CAS  PubMed  Google Scholar 

  95. Guthrie KA, Dugowson CE, Voigt LF, Koepsell TD, Nelson JL (2010) Does pregnancy provide vaccine-like protection against rheumatoid arthritis? Arthritis Rheum 62(7):1842–1848

    PubMed  PubMed Central  Google Scholar 

  96. Adab P, Jiang CQ, Rankin E et al (2014) Breastfeeding practice, oral contraceptive use and risk of rheumatoid arthritis among Chinese women: the Guangzhou biobank cohort study. Rheumatology (Oxford) 53(5):860–866

    Article  Google Scholar 

  97. Chen H, Wang J, Zhou W, Yin H, Wang M (2015) Breastfeeding and risk of rheumatoid arthritis: a systematic review and metaanalysis. J Rheumatol. doi:10.3899/jrheum.150195

    Google Scholar 

  98. Wallenius M, Skomsvoll JF, Irgens LM et al (2010) Postpartum onset of rheumatoid arthritis and other chronic arthritides: results from a patient register linked to a medical birth registry. Ann Rheum Dis 69(2):332–336

    Article  CAS  PubMed  Google Scholar 

  99. Heikkila R, Aho K, Heliovaara M et al (1998) Serum androgen-anabolic hormones and the risk of rheumatoid arthritis. Ann Rheum Dis 57(5):281–285

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Tengstrand B, Carlstrom K, Hafstrom I (2009) Gonadal hormones in men with rheumatoid arthritis—from onset through 2 years. J Rheumatol 36(5):887–892

    Article  CAS  PubMed  Google Scholar 

  101. Pikwer M, Giwercman A, Bergstrom U et al (2014) Association between testosterone levels and risk of future rheumatoid arthritis in men: a population-based case-control study. Ann Rheum Dis 73(3):573–579

    Article  CAS  PubMed  Google Scholar 

  102. Cutolo M, Seriolo B, Villaggio B et al (2002) Androgens and estrogens modulate the immune and inflammatory responses in rheumatoid arthritis. Ann N Y Acad Sci 966:131–142

    Article  CAS  PubMed  Google Scholar 

  103. Schmidt M, Weidler C, Naumann H et al (2005) Androgen conversion in osteoarthritis and rheumatoid arthritis synoviocytes—androstenedione and testosterone inhibit estrogen formation and favor production of more potent 5alpha-reduced androgens. Arthritis Res Ther. 7(5):R938–R948

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Castagnetta LA, Carruba G, Granata OM et al (2003) Increased estrogen formation and estrogen to androgen ratio in the synovial fluid of patients with rheumatoid arthritis. J Rheumatol 30(12):2597–2605

    CAS  PubMed  Google Scholar 

  105. Capellino S, Straub RH, Cutolo M (2014) Aromatase and regulation of the estrogen-to-androgen ratio in synovial tissue inflammation: common pathway in both sexes. Ann N Y Acad Sci 1317:24–31

    Article  CAS  PubMed  Google Scholar 

  106. Baillargeon J, Al Snih S, Raji MA et al (2016) Hypogonadism and the risk of rheumatic autoimmune disease. Clin Rheumatol 35(12):2983–2987

    Article  PubMed  Google Scholar 

  107. Karlson EW, Chibnik LB, McGrath M et al (2009) A prospective study of androgen levels, hormone-related genes and risk of rheumatoid arthritis. Arthritis Res Ther 11(3):R97

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  108. Masi AT, Elmore KB, Rehman AA et al (2013) Lower serum androstenedione levels in pre-rheumatoid arthritis versus normal control women: correlations with lower serum cortisol levels. Autoimmune Dis 2013:593493

    PubMed  PubMed Central  Google Scholar 

  109. Jorgensen KT, Pedersen BV, Jacobsen S, Biggar RJ, Frisch M (2010) National cohort study of reproductive risk factors for rheumatoid arthritis in Denmark: a role for hyperemesis, gestational hypertension and pre-eclampsia? Ann Rheum Dis 69(2):358–363

    Article  CAS  PubMed  Google Scholar 

  110. Jorgensen KT, Harpsoe MC, Jacobsen S, Jess T, Frisch M (2014) Increased risk of rheumatoid arthritis in women with pregnancy complications and poor self-rated health: a study within the Danish National Birth Cohort. Rheumatology (Oxford) 53(8):1513–1519

    Article  Google Scholar 

  111. Nelson JL (2009) Naturally acquired microchimerism: for better or for worse. Arthritis Rheum 60(1):5–7

    Article  PubMed  Google Scholar 

  112. Wolfberg AJ, Lee-Parritz A, Peller AJ, Lieberman ES (2004) Association of rheumatologic disease with preeclampsia. Obstet Gynecol 103(6):1190–1193

    Article  PubMed  Google Scholar 

  113. Rak JM, Maestroni L, Balandraud N et al (2009) Transfer of the shared epitope through microchimerism in women with rheumatoid arthritis. Arthritis Rheum 60(1):73–80

    Article  CAS  PubMed  Google Scholar 

  114. Svendsen AJ, Kyvik KO, Houen G et al (2013) On the origin of rheumatoid arthritis: the impact of environment and genes—a population based twin study. PLoS One 8(2):e57304

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Correspondence to Axel Finckh.

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This article is a contribution to the special issue on Immunopathology of Rheumatoid Arthritis - Guest Editors: Cem Gabay and Paul Hasler

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Alpízar-Rodríguez, D., Finckh, A. Environmental factors and hormones in the development of rheumatoid arthritis. Semin Immunopathol 39, 461–468 (2017). https://doi.org/10.1007/s00281-017-0624-2

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