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Connection between SHBG, chronic inflammation, and rheumatoid arthritis outcomes

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Created On: 30/05/2026

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Key take away

Higher serum SHBG levels significantly increase rheumatoid arthritis risk and are associated with greater frailty, inflammation, and reduced survival outcomes.

Background

Rheumatoid arthritis (RA) is a chronic autoimmune disorder associated with progressive joint damage, cartilage degeneration, bone erosion, systemic inflammation, and increased cardiovascular (CV) risk. Emerging evidence suggests that sex hormone-binding globulin (SHBG), a key regulator of sex hormone bioavailability, may play an important role in RA pathogenesis, disease progression, inflammation, frailty, and long-term survival outcomes. This study investigated the link between serum SHBG levels, RA risk, frailty, inflammatory biomarkers, and CV complications.

Method

Data was analyzed from 25,051 adults enrolled in the National Health and Nutrition Examination Survey between 2013 and 2023. Frailty status was evaluated using a validated 49-item frailty index, while medical history and RA diagnosis were collected through participant questionnaires. Statistical analyses, including logistic regression, mediation analysis, and Kaplan–Meier survival analysis, were performed to assess the relationship between SHBG concentrations, RA prevalence, inflammation, frailty, and survival probability.

Result

Higher serum SHBG concentrations were linked with heightened risk of RA. Both elevated frailty index scores and increased levels of C-reactive protein exhibited strong positive correlations with RA prevalence and disease burden.

The study also revealed that frailty partially mediates the relationship between SHBG and RA, accounting for nearly 24.47% of the association. In addition, RA patients with elevated SHBG levels illustrated considerably lower survival rates, particularly among male patients, highlighting a potential link between SHBG, systemic inflammation, frailty progression, and mortality risk.

Conclusion

Elevated serum SHBG levels may serve as a potential biomarker for RA severity, frailty, CV complications, and reduced survival outcomes. Routine monitoring of SHBG concentrations in RA patients could improve early risk stratification, prognosis evaluation, and personalized disease management strategies. These findings also support the growing role of hormone-related biomarkers in advancing RA diagnosis, prognosis, and long-term patient care.