# Sex differences in primary Sjögren’s disease: prognostic impact on mortality and cancer

## TL;DR

Men with primary Sjögren’s disease face higher risks of death and cancer than women, requiring tailored medical approaches.

## Contribution

This study identifies sex-specific risk factors and outcomes in primary Sjögren’s disease, emphasizing the need for sex-based clinical management.

## Key findings

- Men with primary Sjögren’s disease had a 25.5% mortality rate compared to 8.3% in women.
- Male sex was independently linked to higher cancer incidence (HR = 3.799) and mortality (HR = 1.998).
- Sex-stratified analyses revealed distinct risk profiles for death and cancer in men and women.

## Abstract

To assess the impact of sex on mortality and malignancy in patients with primary Sjögren’s disease (pSD).

This ambispective cohort study included 1,182 pSD patients (1,025 women and 157 men) from the China–Japan Friendship Hospital between 2014–2023 and followed through 2024. Survival outcomes were estimated via Kaplan–Meier curves, and SMRs were calculated. Independent risk factors were identified via multivariate Cox regression, followed by stepwise Cox, sex-stratified and interaction analyses.

During follow-up, 125 deaths (10.6%) and 33 malignancies (2.8%) occurred, both of which were more common in men (log–rank tests, P < 0.001). Overall mortality was markedly higher in men (25.5%, SMR = 4.79) than in women (8.3%, SMR = 2.42). Male sex was independently associated with higher risk of mortality (HR = 1.998, P = 0.004) and cancer incidence (HR = 3.799, P = 0.001). Sex-stratified analyses revealed distinct death–associated factors: interstitial lung disease (ILD), pulmonary infection and ischemic stroke were independently associated with mortality in men, whereas older age, low C3, elevated C-reactive protein and total bilirubin (TBIL) levels were associated with mortality in women. With respect to cancer, longer disease duration, lymphadenopathy, lymphocytopenia, elevated TBIL and hypochloremia were independently associated with cancer risk in women, whereas no variables showed an independent association with cancer risk among men. Interaction analyses demonstrated additive interactions between male sex and elevated ESSDAI scores, as well as male sex and concomitant ILD, in relation to mortality.

Compared with women, men with pSD presented greater risks and distinct risk profiles of death and malignancy. Moreover, male sex was independently associated with adverse outcomes and acted as an important effect modifier, highlighting the need for sex-specific risk stratification and clinical management.

This ambispective cohort study was registered in the Clinical Trial Registry (ID: NCT06528197) on June 27, 2024 and conducted in accordance with the Declaration of Helsinki.

The online version contains supplementary material available at 10.1186/s13293-026-00827-7.

Primary Sjögren’s disease (pSD) is an autoimmune disorder that causes dryness of the eyes and mouth, fatigue, and damage to multiple organs. While pSD mainly affects women, men with the disease tend to experience more severe complications. We enrolled 1,182 patients in China (1,025 women and 157 men) and compared disease features, mortality, and cancer outcomes between male and female patients. During follow-up, about 25% of the men died, compared to about 8% of the women. Sex-stratified analyses revealed distinct prognostic profiles, such as ILD, infections, and ischemic stroke, were particularly dangerous for men, whereas age, inflammation, and low complement levels associated with poor outcomes in women. Male sex remained independently associated with increased risk even after accounting for these factors. These results show that men with pSD represent a distinct, high-risk subgroup who require closer monitoring and tailored treatment strategies. Underscoring the need for sex-specific risk stratification, vigilant monitoring, and tailored management.

The online version contains supplementary material available at 10.1186/s13293-026-00827-7.

Male patients with primary Sjögren’s disease (pSD) exhibited markedly higher mortality (25.5%) and cancer incidence (6.4%) than females (8.3% and 2.2%, respectively).Male sex was independently associated with a higher risk of mortality (HR = 1.998) and cancer incidence (HR = 3.799) after multivariable adjustment, confirming its robust prognostic value.Sex-stratified analyses revealed distinct prognostic profiles: ILD, infection, and ischemic stroke were associated with death in men, whereas older age, low C3, elevated CRP and TBIL were associated with death in women.Interaction analysis demonstrated significant additive interactions between male sex and high ESSDAI scores or concomitant ILD in relation to death. Our findings establish male sex is independently associated with adverse outcomes and acts as a significant effect modifier in pSD, underscoring the need for sex-specific risk stratification, vigilant monitoring, and tailored management.

Male patients with primary Sjögren’s disease (pSD) exhibited markedly higher mortality (25.5%) and cancer incidence (6.4%) than females (8.3% and 2.2%, respectively).

Male sex was independently associated with a higher risk of mortality (HR = 1.998) and cancer incidence (HR = 3.799) after multivariable adjustment, confirming its robust prognostic value.

Sex-stratified analyses revealed distinct prognostic profiles: ILD, infection, and ischemic stroke were associated with death in men, whereas older age, low C3, elevated CRP and TBIL were associated with death in women.

Interaction analysis demonstrated significant additive interactions between male sex and high ESSDAI scores or concomitant ILD in relation to death. Our findings establish male sex is independently associated with adverse outcomes and acts as a significant effect modifier in pSD, underscoring the need for sex-specific risk stratification, vigilant monitoring, and tailored management.

The online version contains supplementary material available at 10.1186/s13293-026-00827-7.