Abstract
Systemic lupus erythematosus (SLE) has a high female predominance with a 9:1 female-to-male sex ratio, but males have poorer clinical outcomes than females. Gonadal hormones may mediate gender differences in SLE, but their role in SLE remains largely uncharacterised. We aimed to investigate a potential association between testicular hypofunction (TH), as a proxy for low testosterone levels, and SLE in males. A retrospective cohort study was conducted by analysing linked English national Hospital Episode Statistics (HES) and mortality data from 1999 to 2011. We calculated rates for SLE following TH, and TH following SLE, stratified and standardised by age, calendar year of first recorded admission, region of residence, and quintile of patients' Index of Deprivation score. The adjusted rate ratio (RR) of SLE following TH was 7.7 (95% confidence interval (95% CI) 2.5-18.1, p < 0.0001). The adjusted RR for TH following SLE was 6.5 (95% CI 2.1-15.1, p < 0.0001). The positive association between TH and SLE supports a hypothesis that low testosterone levels may influence the development of male SLE. Of clinical importance, it suggests that males with SLE are at increased risk of co-morbid TH (regardless of which precedes which) and this may warrant consideration in the management of patients.