Effects of Oral Testosterone Undecanoate (Kyzatrex) Versus Testosterone Gel (Androgel) on Long-Term (to 12 Months) Blood Pressure Levels

Purpose: Oral and injectable testosterone replacement therapies have been reported to increase blood pressure (BP) in hypogonadal men. Less is known about the effects of topical testosterone formulations on BP. Materials and Methods: We studied the effects of a new oral testosterone undecanoate (TU) (Kyzatrex™) and a topical testosterone gel (Androgel™) on BP and heart rate, in a 2:1 randomized trial of men with hypogonadism. Digital BPs and clinical assessments were obtained at baseline and at 90, 180 and 365 days. Results: There were 314 men randomized (mean age 49.7 years, 82% white, and 35% with treated hypertension). The mean changes from baseline in systolic BP were 2.2 mmHg (95% confidence interval [CI] 0.6–3.7) on the oral TU and 3.1 mmHg (95% CI 1.0–5.1) on the topical testosterone at 90 days. Similar findings were seen after 180 and 365 days. Heart rate increased by 4.3 and 2.7 beats/min at 90 days on oral and topical testosterone, respectively. For those men with treated hypertension, changes in systolic BP in the oral TU group were higher compared with those without hypertension, whereas those on topical testosterone had similar increases in systolic BP regardless of hypertension status. Outlier analyses for systolic BP at 90 days demonstrated a higher proportions of subjects with increases of 5 and 10 mmHg postbaseline on topical testosterone gel versus this oral TU. Conclusions: These data demonstrate that the overall effects of the oral TU on BP were comparable with a topical testosterone. In men without hypertension, the oral TU induced smaller changes in BP compared with topical testosterone. Clinical Trial Registration (https://www.clinicaltrials.gov/): NCT04467697.