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

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.