Testosterone Inhibition and Risk of Laryngeal and Hypopharyngeal Squamous Cell Carcinoma in Men

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Importance Laryngeal and hypopharyngeal squamous cell carcinoma most commonly occur in men. It has been hypothesized that testosterone explains this sex difference, but there is a lack of research on the topic. 5α-Reductase inhibitors (5-ARIs) are common medications used for men with benign hyperplasia that inhibit the conversion of testosterone to the bioactive form dihydrotestosterone and, thus, have anti-androgenic properties. Objective To examine whether use of 5-ARIs is associated with lower risk of laryngeal and hypopharyngeal squamous cell carcinoma in men. Design, Setting, and Participants This population-based cohort study included men in the Swedish Prescribed Drugs and Health Cohort from July 1, 2005, to December 31, 2022, with follow-up until December 31, 2023. Exposure At least 2 dispensations of 5-ARIs within 2 years during the study period. Users of 5-ARIs were compared with 5 times as many age- and date-matched men without history of 5-ARI use. Main Outcome and Measures The main outcome was a new diagnosis of laryngeal or hypopharyngeal squamous cell carcinoma during follow-up. Multivariable Cox regression provided hazard ratios with 95% CIs, adjusted for alcohol overconsumption, tobacco smoking, hypertension, hyperlipidemia, and diabetes. Results A total of 253 010 users of 5-ARIs and 1 265 050 nonusers were included (median [IQR] age, 74 [67-80] years). The median (IQR) follow-up time was 5.8 (2.7-10.1) years among the 5-ARI users and 4.7 (1.0-9.4) years among the nonusers. Laryngeal or hypopharyngeal squamous cell carcinoma was diagnosed in 215 (0.1%) of the 5-ARI users and 1131 (0.1%) of the nonusers. Use of 5-ARIs was associated with a 17% lower risk of laryngeal or hypopharyngeal squamous cell carcinoma compared to nonusers (adjusted hazard ratio, 0.83; 95% CI, 0.72-0.96). Conclusions and Relevance In this cohort study, use of 5-ARIs was associated with a decreased relative risk of hypopharyngeal and laryngeal squamous cell carcinoma. This supports a possible partial role of testosterone in the origin and male predominance of these tumors.