Increased risk of autoimmune disorders in infertile men: analysis of US claims data

Aberrations in reproductive fitness may be a harbinger of medical diseases in men. Existing data suggest that female infertility is associated with autoimmune disorders; however, this has not been examined in men. As immune surveillance and hormonal factors can impact male fertility and autoimmunity, we sought to determine the association between male infertility and incident autoimmune disorders. We analyzed subjects from the Truven Health MarketScan claims database from 2001 to 2008. Infertile men were identified through diagnosis and treatment codes. We examined the most common immune disorders, which were identified by ICD9 diagnosis codes. Men diagnosed with an immune disorder at baseline or within 1year of follow-up were excluded. Infertile men were compared to vasectomized men (i.e., men who are likely fertile) and to age-matched control (10:1) group using Cox regression analysis. A total of 33,077 infertile men (mean age of 33years), 77,693 vasectomized men (mean age 35), and 330,770 age-matched control men (mean age 33) were assembled with a total follow-up of 1.49M person-years. Overall, immune disorders were rare in the group with the individual conditions occurring in <0.1% of men. However, infertile men displayed the highest risk of many conditions. Infertile men had a higher risk of developing rheumatoid arthritis compared to both vasectomized men (HR 1.56, 95% CI 1.19-2.05) and age-matched controls (HR 1.29, 95% CI 1.02-1.62). Additionally, this higher risk was seen in general immune disorders (under which systemic lupus erythematosus is categorized) compared to vasectomized men (HR 3.11, 95% CI 2.00-4.86) and age-matched men (HR 2.12, 95% CI 1.52-2.96). This same risk trend was seen in psoriasis, when compared to vasectomized men (HR 1.28, 95% CI 1.09-1.50) and age-matched controls (HR 1.20, 95% CI 1.04-1.37). A similar trend was seen in the analysis comparing infertile men and vasectomized men in developing multiple sclerosis (HR 1.91, 95% CI 1.10-3.31) and Grave's disease (HR 1.46, 95% CI 1.10-1.92), as well as the higher risk of infertile men compared to the age-matched group at developing thyroiditis (HR 1.60, 95% CI 1.02-2.52). The current analysis shows that infertile men have a higher risk of developing certain autoimmune disorders in the years following an infertility evaluation. Specifically, infertile men had higher rates of developing rheumatoid arthritis, multiple sclerosis, psoriasis, thyroiditis, and Grave's disease. Given these findings, further research should focus on confirmation of these associations and elucidation of the pathways between fertility and immunity.