Effects of cumulative lifetime estrogen exposure on the clinical characteristics and courses in postmenopausal women with rheumatoid arthritis

Objectives

To assess the effect of cumulative lifetime estrogen exposure (CLEE) on the course of rheumatoid arthritis (RA).

Methods

A total of 2878 postmenopausal women with RA from the Korean Observational Study Network for Arthritis Cohort were investigated at baseline and followed for 5 years. CLEEs were calculated by combining the reproductive span and duration of postmenopausal hormone replacement therapy. Patients with RA were classified into higher and lower CLEE groups using a median of 34 years.

Results

Patients with RA and a lower CLEE (n = 1602) showed significantly higher disease activity and more radiographic erosion than those with a higher CLEE (n = 1179) at baseline. The lower CLEE group demonstrated worse patient-reported outcomes (PROs) for pain, fatigue, sleep disturbance, functional disability, health-related quality of life, and global assessment of RA than the higher CLEE group at baseline (all P < 0.01). The lower CLEE group showed increased Simplified Disease Activity Index (SDAI) and Health Assessment Questionnaire-Disability Index scores and decreased EQ-5D-utility values over 5 years after adjusting for confounders. Among patients with RA and an SDAI>11 at baseline, the lower CLEE group was significantly less likely to achieve remission after adjusting for confounders (HR, 0.597 [95% CI 0.421–0.848], p = 0.004).

Conclusions

Patients with RA and lower CLEE had higher disease activity, more erosive disease, and worse PROs than those with a higher CLEE. Lower CLEE adversely affects longitudinal changes in disease activity and PROs and is associated with a lower likelihood of achieving clinical remission in RA.