Skip to main content
SpringerLink
Log in

Influence of Gender on Autoimmune Rheumatic Diseases

  • Chapter
  • First Online:
Women's Health in Autoimmune Diseases

  • 439 Accesses

Abstract

Females, while enjoying the advantage of being protected from infections due to their immunoreactivity, are at a higher risk of autoimmune diseases due to the same mechanism. This sexual dimorphism of the immune response in the background of a skewed prevalence of autoimmune diseases in females and the knowledge of the immunomodulatory function of sex steroids indicate a major role of sex hormones as important mediators of the observed clinical gender differences. Recent studies also point toward the reciprocal influence of the sex hormones and microbiome composition in the human body, contributing to the differences in the immune response between females and males. Based on available data, it appears that sex is an important variable to address in future research which may eventually lead to more sex-specific therapy for patients with these diseases. In this narrative review, we appraise how gender has an impact on various autoimmune rheumatic diseases with regard to incidence, disease course, severity, response to treatment, and pathogenesis.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Whitcare CC (2001) Sex differences in autoimmune diseases. Nat Immunol 2:777–780

    Article  CAS  Google Scholar 

  2. Moroni L, Bianchi I, Lleo A (2012) Geoepidemiology, gender and autoimmune diseases. Autoimmun Rev 11:A386–A392

    Article  PubMed  Google Scholar 

  3. Cincinelli G, Generali E, Dudam R, Ravindran V, Selmi C (2018) Why women or why not men? Sex and autoimmune diseases. Indian J Rheumatol 13:44–50

    Article  Google Scholar 

  4. Karlson EW et al (2004) Do breast feeding and other reproductive factors influence future risk of rheumatoid arthritis? Results from the Nurses Health Study. Arthritis Rheum 50:3458–3467

    Article  PubMed  Google Scholar 

  5. Nelson JL et al (1993) Fecundity before disease onset in women with rheumatoid arthritis. Arthritis Rheum 36:7–14

    Article  CAS  PubMed  Google Scholar 

  6. Nelson JL, Ostensen M (1997) Pregnancy and rheumatoid arthritis. Rheum Dis Clin N Am 23:195–212

    Article  CAS  Google Scholar 

  7. Jawaheer D, Olsen J, Hetland ML (2012) Sex differences in response to anti-tumor necrosis factor therapy in early and established rheumatoid arthritis, results from the DANBIO registry. J Rheumatol 39:46–53

    Article  PubMed  Google Scholar 

  8. Sokka T et al (2009) Women men and rheumatoid arthritis: analyses of disease activity, disease characteristics and treatments in the QUEST-RA study. Arthritis Res Ther 11:R7

    PubMed  PubMed Central  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  10. Cutolo M (2009) Androgens in rheumatoid arthritis: when are they effectors? Arthritis Res Ther 11:126

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  11. Tengstrand B, Carlstorm K, Tsai F et al (2003) Abnormal levels of serum DHEA, estrone and estradiol in men with rheumatoid arthritis: high correlation between serum estradiol and current degree of inflammation. J Rheumatol 30:2338–2343

    CAS  PubMed  Google Scholar 

  12. Hughes GC (2012) Progesterone and autoimmune diseases. Autoimmun Rev 11:A502–A514

    Article  CAS  PubMed  Google Scholar 

  13. Burkhardt J et al (2009) Association of the X chromosomal genes TIMP1 and ILR 9 with rheumatoid arthritis. J Rheumatol 36:2149–2157

    Article  CAS  PubMed  Google Scholar 

  14. Somers EC et al (2013) Paternal history of lupus and rheumatoid arthritis and risk in offspring in a nationwide cohort study: does sex matter? Ann Rheum Dis 72:525–529

    Article  CAS  PubMed  Google Scholar 

  15. Costenbader KH, Feskanich D, Stampfer MJ, Karlson EW (2007) Reproductive and menopausal factors and risk of systemic lupus erythematosus in women. Arthritis Rheum 56:1251–1262

    Article  PubMed  Google Scholar 

  16. Clowse ME et al (2005) The impact of increased lupus activity on obstetric outcomes. Arthritis Rheum 52:514–521

    Article  PubMed  Google Scholar 

  17. Mohan MC, Ravindran V (2016) Lupus pregnancies: an Indian perspective. Indian J Rheumatol 11:S2135–S2138

    Google Scholar 

  18. Cooper GS, Dooley MA, Treadwell EL, St Clair EW, Gilkeson GS (2002) Hormonal and reproductive risk factors for the development of systemic lupus erythematosus—results of a population based case-control study. Arthritis Rheum 46:1830–1839

    Article  CAS  PubMed  Google Scholar 

  19. Grimaldi CM, Hill L, Xu X, Peeva E, Diamond B (2005) Hormonal modulation of B cell development and repertoire selection. Mol Immunol 42:811–820

    Article  CAS  PubMed  Google Scholar 

  20. Roubinian J, Talal N, Greenspan J, Goodman J, Siiteri P (1978) Effect of castration and sex hormone treatment on survival, anti nucleic acid antibodies, and glomeruolonephritis in NZB/NZW F1 mice. J Exp Med 147:1568–1583

    Article  CAS  PubMed  Google Scholar 

  21. Ben-Chetrit A, Ben-Chetrit E (1994) Systemic lupus erythematosus induced by ovulation induction treatment. Arthritis Rheum 37:1614–1617

    Article  CAS  PubMed  Google Scholar 

  22. Peeva E, Michael D, Cleary J et al (2003) Prolactin modulates the naïve B cell repertoire. J Clin Invest 111:275–283

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Cohen-Solal JF et al (2008) Hormonal regulation of B cell function and systemic lupus erythematosus. Lupus 17:528–532

    Article  CAS  PubMed  Google Scholar 

  24. Chtinis S et al (2000) The role of X chromosome inactivation in female predisposition to autoimmunity. Arthritis Res 2:399–406

    Article  Google Scholar 

  25. Costenbader KH, Bermas B, Tedesch SK (2013) Sexual disparities in the incidence and course of SLE and RA. Clin Immunol 149:211–218

    Article  PubMed  CAS  Google Scholar 

  26. Dillon S et al (2011) Klinefelter syndrome among men with SLE. Acta Paediatr 100:819–823

    Article  PubMed  PubMed Central  Google Scholar 

  27. Scofield RH et al (2008) Klinefelters syndrome (46 XXY) in male SLE patients: support for the notion of a gene-dose effect from the X chromosome. Arthritis Rheum 58:2511–2517

    Article  PubMed  PubMed Central  Google Scholar 

  28. Sawalha AH et al (2012) Sex specific differences in the relationship between genetic susceptibility, T cell DNA demethylation and Lupus flare activity. J Autoimmun 38:216–222

    Article  CAS  Google Scholar 

  29. Santiago-Raber ML, Kikuchi S, Borel P et al (2008) Evidence for genes in addition to TLR7 in the Yaa translocation linked with acceleration of SLE. J Immunol 181:1556–1562

    Article  CAS  PubMed  Google Scholar 

  30. Christine P, Thomas AM, Maryl L, Bedda LR, Carol AFB (2016) Gender differences in systemic sclerosis: relationship to clinical features, serologic status and outcomes. J Scleroderma Relat Disord 1:177–240

    Article  Google Scholar 

  31. Lambe M, Bjornadal L, Neregard P, Nyren O, Cooper GS (2004) Childbearing and the risk of scleroderma: a population based study in Sweden. Am J Epidemiol 159:162–166

    Article  PubMed  Google Scholar 

  32. Pisa FE, Bovenzi M, Romeo L, Tonello A, Biasi D, Bambara LM, Betta A, Barbone F (2002) Reproductive factors and the risk of scleroderma: an Italian case control study. Arthritis Rheum 46:451–456

    Article  PubMed  Google Scholar 

  33. Arlett CM, Rasheed M, Russo KE, Sawaya HH, Jimenez SA (2002) Influence of prior pregnancies on disease course and cause of death in systemic sclerosis. Ann Rheum Dis 61:346–350

    Article  Google Scholar 

  34. Aida-Yasuoka K, Peoples C, Yasuoka H et al (2013) Estradiol promotes the development of a fibrotic phenotype and is increased in the serum of patients with systemic sclerosis. Arthritis Res Ther 15:R10

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Vermeulen A, Kaufmann JM et al (2002) Estradiol in elderly men. Aging Male 5:98–102

    Article  CAS  PubMed  Google Scholar 

  36. Straub RH, Zeuner M, Lock G, Scholmerich J, Lang B (1997) High prolactin and low DHEA sulphate serum levels in patients with severe systemic sclerosis. Br J Rheumatol 36:426–432

    Article  CAS  PubMed  Google Scholar 

  37. Invernizzi P, Miozzi M, Selmi C, Persani L, Battezzati PM, Zuin M et al (2005) X-chromosome monosomy: a common mechanism for autoimmune diseases. J Immunol 175:575–578

    Article  CAS  PubMed  Google Scholar 

  38. Velasco G, Savarese V, Sandorfi N, Jimenez SA, Jabbour S (2011) 46XX SRY positive male syndrome presenting with primary hypogonadism in the setting of scleroderma. Endocr Pract 17:95–98

    Article  PubMed  Google Scholar 

  39. Ramírez Sepúlveda JI, Kvarnström M, Brauner S, Baldini C, Wahren-Herlenius M (2017) Difference in clinical presentation between women and men in incident primary Sjögren’s syndrome. Biol Sex Differ 8:16

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  40. Landi M, Maldonado-Ficco H, Perez-Alamino R et al (2016) Gender differences among patients with primary ankylosing spondylitis and spondylitis associated with psoriasis and inflammatory bowel disease in an iberoamerican spondyloarthritis cohort. Medicine (Baltimore) 95:e5652

    Article  CAS  Google Scholar 

  41. Ostensen M, Fuhrer L, Mathieu R, Seitz M, Villiger PM (2004) A prospective study of pregnant patients with rheumatoid arthritis and ankylosing spondylitis using validated clinical instruments. Ann Rheum Dis 63:1212–1217

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Wallenius M, Skomsvoll JF, Irgens LM, Salvesen KA et al (2011) Pregnancy and delivery in women with chronic inflammatory arthritides with a specific focus on the first birth. Arthritis Rheum 63:1534–1542

    Article  PubMed  Google Scholar 

  43. Katz PP (2006) Childbearing decisions and family size among women with rheumatoid arthritis. Arthritis Rheum 55:217–223

    Article  PubMed  Google Scholar 

  44. Tsui HW et al (2005) ANKH variants associated with ankylosing spondylitis: gender differences. Arthritis Res Ther 7:513–525

    Article  CAS  Google Scholar 

  45. Elena G, Carlo A et al (2016) Sex differences in the treatment of psoriatic arthritis: a systematic literature review IMAJ. Vol 18:203–208

    Google Scholar 

  46. Chiu HY, Wang TS, Chan CC et al (2014) Human leukocyte antigen Cw06 as a predictor for clinical response to ustekinumab, an interleukin-12/23 blocker in Chinese patients with psoriasis: a retrospective analysis. Br J Dermatol 171:1181–1188

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Lifeworth Hospital, Raipur, Chhattisgarh, India

    Arun Kumar Kedia

  2. Centre for Rheumatology, Calicut, Kerala, India

    Vinod Ravindran

Authors
  1. Arun Kumar Kedia
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Vinod Ravindran
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Department of Internal Medicine, PGIMER, Chandigarh, India

    Shefali Khanna Sharma

Ethics declarations

Funding

None.

Conflict of Interest

Arun Kumar Kedia declares that he has no conflict of interest. Vinod Ravindran declares that he has no conflict of interest.

Ethical Approval

This article does not contain any studies with human participants performed by any of the authors.

Rights and permissions

Reprints and permissions

Copyright information

© 2020 Springer Nature Singapore Pte Ltd.

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Kedia, A.K., Ravindran, V. (2020). Influence of Gender on Autoimmune Rheumatic Diseases. In: Sharma, S. (eds) Women's Health in Autoimmune Diseases. Springer, Singapore. https://doi.org/10.1007/978-981-15-0114-2_2

Download citation

  • DOI: https://doi.org/10.1007/978-981-15-0114-2_2

  • Published:

  • Publisher Name: Springer, Singapore

  • Print ISBN: 978-981-15-0113-5

  • Online ISBN: 978-981-15-0114-2

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation