Background/Purpose: Lifetime exposure to female sex hormones may play a role in the development and severity of rheumatoid arthritis (RA). These same hormones have also been found to play a role in the development of cardiovascular disease (CVD) in women. Since RA is associated with an increased risk of CVD, the purpose of this study was to determine if early menopause, representing a surrogate for lower lifetime exposure to female sex hormones, affects the risk of developing CVD in women with RA.

Methods: A population-based inception cohort of 600 women with RA who first fulfilled 1987 ACR criteria for RA between 1955 and 2007 was assembled and followed until death, migration or 12/31/2008. Age at menarche, gravidity, parity, age at menopause, and duration, if any, of hormone replacement therapy (HRT), along with occurrence of CVD (including coronary artery disease, heart failure, cerebrovascular disease and peripheral vascular disease) was ascertained by review of medical records. Cox proportional hazard models were used to compare women within this cohort who underwent early menopause, defined as natural or artificial menopause at age ≤ 45 years, to those within the cohort who did not undergo early menopause.

Results: This study included 600 women with RA age ≥ 45 years at diagnosis, of whom 199 experienced early menopause (mean age ± SD: 64.3 ± 12.0 years; 67.x % rheumatoid factor (RF) positive) and 401 did not (mean age: 62.8 ± 11.4 years; 64.9% RF positive). The mean age at menopause in those who experienced early menopause was 40.9 ± 5.0 years, while in those who did not the mean age at menopause was 50.7 ± 2.8 years. Among women without prior CVD, 73 with early menopause and 132 without early menopause developed CVD during a mean follow-up of 11.8 years. Women who underwent early menopause were at significantly higher risk for developing CVD when compared to women who did not experience early menopause (hazard ratio (HR): 1.41; 95% CI: 1.05-1.91, adjusted for age, calendar year of RA diagnosis and cardiovascular risk factors including smoking status, body mass index at RA diagnosis, diabetes mellitus and hypertension). This difference remained significant when age of menopause was defined as the end of HRT for women with artificial menopause who started HRT therapy at the time of artificial menopause (HR: 1.40; 95% CI: 1.03-1.88). CVD risk was increased in women with higher gravidity and parity (HR 1.06 per pregnancy increase; 95% CI 1.004-1.12 and HR 1.07 per 1 birth increase, 95% CI 1.01-1.14 respectively). There was a strong non-linear relationship between gravidity and parity and cardiovascular outcomes, whereby the increase risk of CVD was detected only at very high values (>7) of gravidity and parity. No associations were found between the development of CVD and cause of early menopause (natural vs. artificial), the use of HRT or the length of time on HRT.

Conclusion: The risk of CVD in women with RA was significantly higher in those who experience early menopause, and like other known risk factors should increase clinician concern for development of CVD in these patients. Further investigation is needed to determine the role that female sex hormones play in the development of CVD in women with RA.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/the-influence-of-early-menopause-on-cardiovascular-risk-in-women-with-rheumatoid-arthritis/