Could testosterone be fueling certain throat cancers?

Clinical takeaway: Men taking 5α-reductase inhibitors for benign prostatic hyperplasia had a modestly lower risk of developing laryngeal or hypopharyngeal squamous cell carcinoma than nonusers in a large observational study. The findings are not sufficient to support use of these drugs for cancer prevention but may provide insight into the biologic role of testosterone in these malignancies.

Head and neck cancers, including laryngeal and hypopharyngeal cancers, occur roughly four times as often in men as in women. While tobacco and alcohol remain the major risk factors, evidence of androgen receptor expression in these tumors has fueled interest in a possible role for testosterone signaling.

Researchers analyzed data from more than 1.5 million Swedish men (median age, 74 years), including 253,010 users of 5α-reductase inhibitors (5-ARIs) and 1.27 million matched nonusers. Participants were followed for up to 17 years. Median follow-up among users was 5.8 years.

During follow-up, laryngeal or hypopharyngeal squamous cell carcinoma developed in 215 men taking 5-ARIs and 1,131 nonusers. After adjustment for smoking- and alcohol-related diagnoses, hypertension, hyperlipidemia, and diabetes, 5-ARI use was associated with a 17% lower relative risk of developing either cancer.

The association appeared to be driven largely by hypopharyngeal cancer. Men taking 5-ARIs experienced a 31% lower relative risk of hypopharyngeal squamous cell carcinoma, based on 32 cases among users versus 212 among nonusers. A separate analysis of laryngeal cancer showed a 14% lower relative risk, although the finding did not reach statistical significance.

The absolute difference in hypopharyngeal cancer risk was less than 0.1%, reflecting the rarity of these cancers. The findings support further research into whether 5-ARIs could have a role in prevention.

“This large-scale and population-based cohort study suggests that use of 5-ARIs is associated with a lower relative risk of developing laryngeal and hypopharyngeal squamous cell carcinoma...This finding points toward a role of testosterone in the origin of these cancers,” the authors wrote.

Source: Gottlieb-Vedi E, et al. (2026 Oct 1) JAMA Otolaryngol Head Neck Surg. Testosterone Inhibition and Risk of Laryngeal and Hypopharyngeal Squamous Cell Carcinoma in Men