Association between antibiotic use and Graves' disease: A cohort study.

Objective

Graves' disease (GD) is the predominant cause of hyperthyroidism and a multifactorial autoimmune disorder in which genetic susceptibility interacts with environmental exposures. Although gut microbiota alterations have been reported in GD, the association between antibiotic exposure and GD risk remains unclear.

Design

This population-based retrospective cohort study used the Korean National Health Insurance Service database and included 311,911 adults aged ≥40 years who underwent health screening in 2005-2006.

Methods

Cumulative antibiotic prescriptions during the five years before the index date were categorized as none, 1-14, 15-60, and ≥61 days. The number of distinct antibiotic classes prescribed (0, 1, 2, 3, and ≥4) was also evaluated. Cox proportional hazards regression estimated adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) after adjustment for various covariates.

Results

Longer cumulative antibiotic exposure was associated with higher GD risk (P for trend <0.0001). Compared with non-users, aHRs (95% CIs) for 1-14, 15-60, and ≥61 days of antibiotic exposure were 1.23 (1.03-1.47), 1.43 (1.20-1.70), and 1.43 (1.18-1.73), respectively. Exposure to ≥4 antibiotic classes was also associated with higher GD risk (aHR, 1.50; 95% CI, 1.25-1.80; P for trend <0.0001). The incidence rate increased from 4.6 per 10,000 person-years among non-users to 6.3, 8.1, and 8.2 per 10,000 person-years for 1-14, 15-60, and ≥61 days, respectively.

Conclusion

Prolonged antibiotic exposure and exposure to a greater number of antibiotic classes were associated with a modest relative increase in subsequent GD risk, although absolute differences were small. These observational findings do not establish causality and warrant confirmation.