Sex and gender differences in rheumatology: clinical impact and future directions

Volkmann, E. R. & Feghali-Bostwick, C. Sex- and gender-based personalized medicine in rheumatology. Nat. Rev. Rheumatol. 21, 251–252 (2025).

Article  PubMed  PubMed Central  Google Scholar 

Ngo, S. T., Steyn, F. J. & McCombe, P. A. Gender differences in autoimmune disease. Front. Neuroendocrinol. 35, 347–369 (2014).

Article  CAS  PubMed  Google Scholar 

Zhang, Q. et al. Epidemiological considerations in transgender health: a systematic review with focus on higher quality data. Int. J. Transgender Heal. 21, 125–137 (2020).

Article  Google Scholar 

Salgado, E. et al. Inmune-mediated inflammatory rheumatic diseases in transgender people: a scoping review. Semin. Arthritis Rheum. 52, 151920 (2022).

Article  PubMed  Google Scholar 

Mathias, K. et al. Challenges of caring for transgender and gender diverse patients with rheumatic disease: presentation of seven patients and review of the literature. Curr. Opin. Rheumatol. 35, 117–127 (2023).

Article  PubMed  Google Scholar 

Sax, L. How common is intersex? A response to Anne Fausto-Sterling. J. Sex. Res. 39, 174–178 (2002).

Article  PubMed  Google Scholar 

Sawalha, A. H., Harley, J. B. & Scofield, R. H. Autoimmunity and Klinefelter’s syndrome: when men have two X chromosomes. J. Autoimmun. 33, 31–34 (2009).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Aletaha, D. & Smolen, J. S. Diagnosis and management of rheumatoid arthritis: a review. JAMA 320, 1360–1372 (2018).

Article  PubMed  Google Scholar 

GBD 2021 Rheumatoid Arthritis Collaborators. Global, regional, and national burden of rheumatoid arthritis, 1990–2020, and projections to 2050: a systematic analysis of the Global Burden of Disease Study 2021. Lancet Rheumatol. 5, e594–e610 (2023).

Article  Google Scholar 

Finckh, A. The epidemiology of RA. Nat. Rev. Rheumatol. 21, 701–702 (2025).

Article  PubMed  Google Scholar 

Palm, O. & Purinszky, E. Women with early rheumatoid arthritis are referred later than men. Ann. Rheum. Dis. 64, 1227–1228 (2005).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Coffey, C. M., Davis, J. M. III & Crowson, C. S. The impact of gender on time to rheumatoid arthritis classification: a retrospective analysis of a population-based cohort. Rheumatol. Int. 39, 2025–2030 (2019).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Stack, R. J. et al. Delays between the onset of symptoms and first rheumatology consultation in patients with rheumatoid arthritis in the UK: an observational study. BMJ Open 9, e024361 (2019).

Article  PubMed  PubMed Central  Google Scholar 

Lard, L. R., Huizinga, T. W., Hazes, J. M. & Vliet Vlieland, T. P. Delayed referral of female patients with rheumatoid arthritis. J. Rheumatol. 28, 2190–2192 (2001).

CAS  PubMed  Google Scholar 

van Dijk, B. T. & van der Helm-van Mil, A. H. M. Delayed referral of female patients with rheumatoid arthritis: where are we now? A study spanning 3 decades. J. Rheumatol. 49, 1402–1403 (2022).

Article  PubMed  PubMed Central  Google Scholar 

Tarannum, S. et al. Understanding sex-related differences in healthcare utilisation among patients with inflammatory arthritis: a population-based study. Ann. Rheum. Dis. 82, 283–291 (2023).

Article  PubMed  Google Scholar 

Favalli, E. G. et al. Sex and management of rheumatoid arthritis. Clin. Rev. Allergy Immunol. 56, 333–345 (2019).

Article  PubMed  Google Scholar 

Ifesemen, O. S. et al. Fatigue in early rheumatoid arthritis: data from the early rheumatoid arthritis network. Rheumatol 61, 3737–3745 (2022).

Article  CAS  Google Scholar 

Goulden, B. et al. The impact of pregnancy on future health in rheumatoid arthritis: a systematic review of the literature. Autoimmun. Rev. 24, 103808 (2025).

Article  PubMed  Google Scholar 

Namavari, N., Jokar, M., Ghodsian, A., Jahromi, H. K. & Rahmanian, V. Menopausal state and rheumatoid arthritis: a systematic review and meta-analysis. BMC Rheumatol. 8, 48 (2024).

Article  PubMed  PubMed Central  Google Scholar 

Guimarães, C. et al. Hormone therapy in menopause increases rheumatoid arthritis risk: a systematic review and meta-analysis. Semin. Arthritis Rheum. 77, 152935 (2026).

Article  PubMed  Google Scholar 

Marino, A. et al. Association between the use of oral contraceptives and the development of rheumatoid arthritis: a systematic review and meta-analysis. J. Clin. Med. 14, 2710 (2025).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Steffen, A., Holstiege, J., Klimke, K., Akmatov, M. K. & Bätzing, J. Patterns of the initiation of disease-modifying antirheumatic drugs in incident rheumatoid arthritis: a German perspective based on nationwide ambulatory drug prescription data. Rheumatol. Int. 38, 2111–2120 (2018).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Vela-Casasempere, P. et al. Gender differences in clinical and prescribing characteristics of biologic and targeted synthetic drugs in naïve patients with rheumatoid arthritis: data from BIOBADASER III registry. Arthritis Res. Ther. 27, 103 (2025).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Bécède, M. et al. Risk profiling for a refractory course of rheumatoid arthritis. Semin. Arthritis Rheum. 49, 211–217 (2019).

Article  PubMed  Google Scholar 

Capelusnik, D. & Aletaha, D. Baseline predictors of different types of treatment success in rheumatoid arthritis. Ann. Rheum. Dis. 81, 153–158 (2022).

Article  CAS  PubMed  Google Scholar 

Fang, L. et al. Impact of sex on clinical response in rheumatoid arthritis patients treated with biologics at approved dosing regimens. J. Clin. Pharmacol. 60 (Suppl 2), S103–S109 (2020).

CAS  PubMed  Google Scholar 

Lend, K. et al. Sex differences in remission rates over 24 weeks among three different biological treatments compared to conventional therapy in patients with early rheumatoid arthritis (NORD-STAR): a post-hoc analysis of a randomised controlled trial. Lancet Rheumatol. 4, e688–e698 (2022).

Article  CAS  PubMed  Google Scholar 

Lauridsen, K. B. et al. Sex differences in treatment response in patients with rheumatoid arthritis treated with tumour necrosis factor inhibitor: a cohort study from the DANBIO registry. Scand. J. Rheumatol. 54, 252–262 (2025).

Article  CAS  PubMed  Google Scholar 

Ahlmén, M., Svensson, B., Albertsson, K., Forslind, K. & Hafström, I. Influence of gender on assessments of disease activity and function in early rheumatoid arthritis in relation to radiographic joint damage. Ann. Rheum. Dis. 69, 230–233 (2010).

Article  PubMed  Google Scholar 

Barnabe, C. et al. Sex differences in pain scores and localization in inflammatory arthritis: a systematic review and metaanalysis. J. Rheumatol. 39, 1221–1230 (2012).

Article  PubMed  Google Scholar 

Nishino, T., Hashimoto, A., Tohma, S. & Matsui, T. Comprehensive evaluation of the influence of sex differences on composite disease activity indices for rheumatoid arthritis: results from a nationwide observational cohort study. BMC Rheumatol. 7, 4 (2023).

Article  PubMed  PubMed Central  Google Scholar 

Koc, G. H., Looijen, A. E. M., van der Horst-Bruinsma, I. E. & de Jong, P. H. P. Sex differences in rheumatoid arthritis: new insights from clinical and patient-reported outcome perspectives. J. Rheumatol. 52, 553–562 (2025).

Article  PubMed 

Comments (0)

No login
gif