Background/Purpose: RA-associated lung diseases (RA-LD) such as RA-associated interstitial lung disease (RA-ILD) and RA-associated bronchiectasis (RA-BR) are more common in men, but risk rises with age for both men and women. However, no studies have examined the role of reproductive factors, such as time since menopause, in RA-LD risk among women.

Methods: We performed a case-control study of reproductive factors and RA-LD risk in women from two established US prospective RA cohorts (an institutional registry and a health care system biobank) who had clinically indicated high-resolution chest computed tomography (CT) imaging. All women had RA by 2010 ACR/EULAR criteria. RA-LD cases were identified using research review of chest CT images by thoracic radiologists and detailed medical record review confirming that participants met criteria for RA-LD. Controls had RA and no evidence of lung disease based on medical record review and were matched to cases by age and RA duration. The index date for cases was the date of RA-LD diagnosis and the index date was assigned to RA-noLD controls. We analyzed women who answered surveys about reproductive health. The primary analysis investigated years since menopause for RA-LD risk. Secondary analyses included age at menarche, pregnancies, ovulatory-years, type of menopause, and age at menopause as well as RA-ILD and RA-BR risk. We used logistic regression to estimate odds ratios for RA-LD, adjusting for chronological age, smoking, and serostatus.

Results: We analyzed 99 RA-LD cases (mean age 65.5 years) and 170 RA-noLD controls (mean age 63.4 years) who answered surveys about female reproductive factors. RA-LD cases had shorter duration of ovulatory-years (mean 33.8 vs. 35.4 years, p=0.037), younger age at menopause (mean 47.0 vs. 48.5 years, p=0.038), and longer time since menopause (mean 18.4 years vs. 14.8 years, p=0.013) than RA-noLD controls (Table 1). In the primary analysis, time since menopause was significantly associated with RA-LD (adjusted OR 1.05 per year, 95%CI 1.004 to 1.10; p=0.034) (Table 2). In the secondary analyses, menarche at age 10 years or younger was associated with higher RA-LD risk than menarche at age 11 to 14 years (adjusted OR 2.54, 95%CI 1.15 to 5.60). Higher ovulatory-years had a trend towards lower RA-LD risk but was not statistically significant after adjustment (OR 0.96 per year, 95%CI 0.92 to 1.003). Younger age at menopause was associated with RA-LD risk (adjusted OR 2.06, 95%CI 1.03 to 4.11 for onset < 45 years vs. 50 to 54 years). There was no association of iatrogenic menopause (surgical, radiation, or chemotherapy) with RA-LD risk. When analyzing RA-ILD and RA-BR separately, results for RA-ILD risk were similar to RA-LD risk (Table 3).

Conclusion: In this first study examining reproductive factors and RA-LD risk in women, longer time since menopause was associated with higher RA-LD risk. Younger ages at menarche and at menopause were each associated with higher RA-LD risk, and results were similar for RA-ILD. Results were not explained by chronological age, RA duration, serostatus, or smoking. These findings suggest that menopausal factors, such as lack of estrogen, may place older women with RA at risk for LD.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/reproductive-factors-and-risk-of-rheumatoid-arthritis-associated-interstitial-lung-disease-or-bronchiectasis-in-women/