Levothyroxine is a widely prescribed medication for the treatment of an underactive thyroid. The relationship between levothyroxine use and cancer risk is largely underdetermined. To investigate the magnitude of the possible association between levothyroxine use and cancer risk, this retrospective case-control study was conducted using Taiwan’s Health and Welfare Data Science Center (HWDC) database. Cases were defined as all patients who were aged ≥20 years and had a first-time diagnosis of any site cancer for the period between 2001 and 2011. Multivariable conditional logistic regression models were used to calculate an adjusted odds ratio (AORs) to reduce potential confounding factors. A total of 601,733 cases and 2,406,932 controls were included in this current study. Levothyroxine users showed a 50% higher risk of any site cancer (AOR: 1.50, 95% CI: 1.46-1.54; p<0.0001) compared with non-users. Additionally, significant increased risks were also observed in brain cancer (AOR: 1.90, 95% CI: 1.48-2.44; p<0.0001), skin cancer (AOR: 1.42, 95% CI: 1.17-1.72; p<0.0001), pancreatic cancer (AOR: 1.27, 95% CI: 1.01-1.60; p=0.03), and female breast cancer (AOR: 1.24, 95% CI: 1.15-1.33; p<0.0001). Our study results showed that levothyroxine use was significantly associated with an increased risk of cancer, particularly brain, skin, pancreatic, and female breast cancers. Since levothyroxine still remains a highly effective therapy for hypothyroidism; therefore, physicians should carefully consider levothyroxine therapy, and monitor patients' condition timely for avoiding the unexpected consequence. Additional studies are needed to confirm these findings and to evaluate the potential biological mechanism.
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