HORMONAL transitions across the lifespan may play a critical role in shaping susceptibility to Sjogren’s disease, offering new insight into its well-known female predominance. A large-scale analysis of electronic health records suggests that fluctuations in sex hormones, rather than abnormal hormone levels, may align with shifts in disease risk across different life stages.
Hormonal Transitions and Sjogren’s Disease Risk
Sjogren’s disease has long been characterized by a strong female predominance, often cited as a 9:1 female-to-male ratio. However, this study challenges that static view by demonstrating that sex-specific prevalence varies significantly with age.
Analysis of over 100,000 patients with Sjogren’s disease and more than 1.3 million controls revealed distinct, non-linear patterns in male prevalence. Rates were highest in early childhood at 30.1%, declined sharply during late puberty and adulthood to 9.8%, and increased again in older age to 13.5%. These shifts closely mirrored natural changes in testosterone and estradiol levels across the lifespan.
Age-Dependent Hormonal Dynamics
To better understand these patterns, researchers integrated population-level hormone data and evaluated associations between hormone fluctuations and disease prevalence. Notably, hormone concentrations themselves did not significantly differ between patients and controls.
This finding suggests that the timing of hormonal transitions, rather than absolute hormone levels, may influence autoimmune susceptibility. Periods such as puberty and aging, which involve significant endocrine changes, appear to correspond with key inflection points in Sjogren’s disease risk.
Rethinking Sex Bias in Autoimmune Disease
These findings challenge the traditional perception of Sjogren’s disease as uniformly female-dominated and instead support a more dynamic model of risk. The evolving sex distribution across age groups highlights the importance of considering hormonal context when evaluating autoimmune disease susceptibility.
By linking physiological hormonal transitions to disease patterns, this study provides a new framework for understanding how immune responses may be modulated across the lifespan. It also underscores the need for age- and sex-specific approaches in both research and clinical management of Sjogren’s disease.
Reference
Diggins EC et al. Hormonal transitions across the lifespan shape susceptibility to Sjogren’s disease. Rheumatology. 2026;65(3).
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