Menopause and Risk of Seronegative Rheumatoid Arthritis
Genetic and environmental risk factors have been long identified as promoting the occurrence and development of rheumatoid arthritis (RA) phenotypes associated with anti-citrullinated peptide (ACPA) or rheumatoid factor (RF) antibodies. Those favoring seronegative RA are less well known.
However, menopause and its impact on the risk of RA: hormonal fluctuations related to this period of life may be involved in the pathogenesis of the disease. For the time being, the data linking the occurrence of RA with menopause reveal rather contrasting results and have not described its association in light of the disease phenotype. A study has just been published as a result of collecting the information of two large cohorts.
Methodology
- The analysis wasconducted from the Nurses' Health Studies cohort of 1976-2010 (NHS) and 1989-2011 (NHS II), with 120,700 nurses aged 30 to 55 and 116,430 nurses aged 25 to 42 years respectively.
- These women were asked to complete questionnaires on their lifestyle and health status every two years.Incident cases of RA were investigated and prevalent cases excluded from the analysis. Pre-menopausal periods, age of onset and nature of menopause (natural or not) were used to classify women as part of the analysis. The use of hormone replacement therapy (HRT) was also identified.
- Women who had a diagnosis of RA were given a complete questionnaire on Connective Tissue Disease Screening Questionnaire, which was analyzed by two rheumatologists to confirm the diagnosis. Data from the biological tests were collected and analyzed. RA was considered seropositive when participants had a positive RF and/or ACPA.
- Multivariate statistical analysis was carried out taking into account potential confounding factors: age, median income, BMI, smoking and pack-years, parity and lactation.
Results
- The study population consisted of 109,443 women (2,498,323 patient-years) from the NHS study and 112,523 women (1,987,756 patient-years) from the NHS II study.Among these, 1,096 cases of RA were identified (including 401 seronegative and 695 seropositive cases).
- The well-known age distribution of the disease was observed: women aged 45 and older possessed an increased RA risk compared with those aged 25 to 44. Between ages 45 and 49, pooled hazard ratio [HR] was 1.5 (95% CI, 1.2-1.9), increasing to 2.0 at ages 50 to 54 and 2.3 at ages 55 to 59 (95% CI, 1.6-2.5 and 1.7-3.2, respectively). Patterns were similar among seronegative RA cases.
- Postmenopausal women had an increased risk of seronegative RA vs premenopausal women (NHS HR: 1.8; 95% CI, 1.1-3.0; NHSII HR: 2.4; 95% CI, 1.4-3.9). Regardless of the age at menopause onset, menopause was associated with an increased seronegative RA risk. However the highest risk had women with natural menopause occurrence at age ≤ 44 years (NHS HR: 2.7; 95% CI, 1.4-5.3; NHSII HR, 2.6; 95% CI, 1.1-6.2).
- No association was observed between HRT use and the risk of seronegative or seropositive RA, except that HRT use of more than eight years was associated with increased risk of seropositive RA (pooled HR 1.4, 95% CI 1.1-1.9).
Why is this important?
This new data shed light on the potentially different risk factors of both seronegative and seropositive rheumatoid arthritis. The authors of the study emphasized on that there could be potential differences in the etiology of those RA subtypes.
Reference
Tags: rheumatoid arthritis, menopause, antibodies