Early menopause is associated with higher disease activity independent of inflammation in postmenopausal-onset rheumatoid arthritis

Abstract

Objective

Early menopause (EM, age ≤ 45 years) is associated with an increased risk of developing rheumatoid arthritis (RA). We aimed to investigate its impact on disease characteristics in RA patients.

Methods

This cross-sectional study included natural post-menopausal RA patients from an observational RA cohort recruited between January 2015 and October 2023. Demographic characteristics and clinical data were collected. Patients were divided into EM and usual menopause (UM, menopause age > 45 years) groups. Patients-reported outcomes (PROs, included patient global assessment of disease activity [PtGA], pain visual analogue scale [VAS] and Stanford health assessment questionnaire disability index [HAQ-DI]), and PROs-associated indicators (included 28-joint tender joint count [TJC28] and provider global assessment of disease activity [PrGA]) were assessed.

Results

Among 1427 female RA patients, 557 natural post-menopausal RA patients were enrolled. The peak menopause age was between 46 and 50 years, with RA incidence peaking 5 years post-menopause. Compared with UM patients, RA patients with natural EM (n = 98,17.6%) exhibited more serious disease, including worse PROs and PROs-associated indicators, as well as higher C-reactive protein (CRP, all P < 0.05). Among 344 (61.8%) patients with RA onset after menopause, EM patients (n = 62, 18.0%) were characterized with worse PROs and PROs-associated indicators than those with UM patients (all P < 0.05), but no difference in inflammatory makers. Multivariate linear regression showed that menopause age was independently and negatively associated with PROs, including PtGA (β = -0.872, 95% CI -1.619, -0.125), HAQ-DI (β = -0.646, 95% CI -1.059, -0.233) in RA patients especially in those onset after menopause (PtGA [β = -1.028, 95% CI -2.022, -0.034]; HAQ-DI [β = -0.916, 95% CI -1.461, -0.370]).

Conclusion

Early menopause impacts on PROs independent of inflammation in patients with RA especially in those with postmenopausal-onset RA, which imply the importance of differentiation of non-inflammatory disease activity.