Female reproductive status and exogenous sex hormone use in rheumatoid arthritis patients treated with tocilizumab and csDMARDs

Rheumatology (Oxford). 2023 Feb 1;62(2):583-595. doi: 10.1093/rheumatology/keac357.


Objectives: Sex is well known to influence risk, severity and treatment outcomes of RA, although the underlying causes are uncertain. The aim of this research was to examine whether factors influencing female sex hormones (reproductive status and exogenous sex hormone use) are associated with the efficacy of DMARDs.

Methods: Individual participant data were pooled from five phase 3 clinical trials where RA patients were treated with tocilizumab and/or conventional synthetic DMARDs. The primary outcome was the time to first remission according to the Simplified Disease Activity Index. The relationship between menopausal status or use of exogenous sex hormones and the time of first remission was assessed via Cox proportional analysis. Analysed data included sex, baseline menopausal status (premenopausal, perimenopausal, early postmenopausal and postmenopausal), participant age, body mass index, race, number of previous DMARDs and baseline disease activity.

Results: Analysis included 4474 female patients, of whom 2817 (62.9%) were postmenopausal, 202 (4.5%) were early postmenopausal, 1021 (22.8%) were premenopausal and 414 (9.2%) were perimenopausal. Of these, 221 (7.8%), 13 (6.4%), 255 (25%) and 47 (11.4%), respectively, were taking exogenous sex hormones. In the pooled analysis, perimenopausal status was associated with reduced remission compared with premenopausal status [adjusted HR 0.78 (95% CI 0.61, 0.99)]. Sex hormone use was associated with significantly higher remission [adjusted HR 1.20 (95% CI 1.01, 1.43)].

Conclusion: Perimenopausal women were less likely to achieve remission compared with premenopausal RA patients. The use of exogenous sex hormones appeared to be associated with more frequent remission in female RA patients, particularly those who were perimenopausal and early postmenopausal, although further research is required to confirm and identify the drivers for this observation and how it interacts with menopausal status.

Keywords: RA; csDMARDs; early post-menopausal; exogenous sex hormone; perimenopausal; remission; tocilizumab.

MeSH terms

  • Antibodies, Monoclonal, Humanized / adverse effects
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Antirheumatic Agents* / adverse effects
  • Antirheumatic Agents* / therapeutic use
  • Arthritis, Rheumatoid* / drug therapy
  • Female
  • Gonadal Steroid Hormones* / adverse effects
  • Humans
  • Perimenopause / drug effects
  • Postmenopause / drug effects


  • Antibodies, Monoclonal, Humanized
  • Antirheumatic Agents
  • Gonadal Steroid Hormones
  • tocilizumab