Age-dependent sex disparities in Sjogren's disease prevalence align with natural hormone fluctuations

Sjogrens Disease (SjD), like many autoimmune diseases, shows a strong female-to-male sex bias, raising the possibility of a hormone-mediated mechanism. However, specific hormonal drivers and the underlying mechanisms remain unclear. In this study, we analyze a electronic health record dataset containing >100,000 SjD patients, allowing for a comprehensive statistical investigation into sex bias and serum hormone levels associated with SjD susceptibility. Focusing on testosterone, estradiol, and sex hormone-binding globulin (SHBG), our analysis reveals an age-dependent trend in SjDs sex bias, with a substantially reduced female bias observed in pediatric cases. This finding, alongside statistical modeling, suggests that testosterone or estradiol may influence the sex disparity in SjD prevalence, with distinct effects at different life stages. Specifically, we observe a higher percentage of male SjD patients in early childhood (30.06%, [CI: 26.16-34.11]), declining sharply in late pubescence into adulthood (9.85% [CI: 9.51-10.16]), followed by a secondary steady increase in male prevalence among older adults (13.50% [CI: 13.25-13.76]). Our models indicate that these shifts in sex bias align with typical age-related hormonal changes rather than abnormal levels, suggesting that natural hormone fluctuations may play a significant role in modulating disease susceptibility. This research not only refines our understanding of SjD but also underscores the importance of hormone-level monitoring in future SjD studies and potential therapeutic strategies. Advanced studies are required to further clarify whether testosterone or estradiol is the primary mediator of these trends, promising new insights into hormone-linked pathways and autoimmune disease pathogenesis.