Single-arm study of testosterone gel replacement therapy and ambulatory blood pressure outcomes in men with hypogonadism.

Background and objective: Studies examining ambulatory blood pressure (BP) response to testosterone replacement therapy are needed owing to inconsistent prior findings across formulations. This study assessed testosterone gel 1.62% and 24-h ambulatory BP.

Materials and methods: Single-arm non-inferiority trial (NCT04274894) conducted at 36 US sites enrolled 246 men with hypogonadism (mean age, 57.6 years; mean office systolic/diastolic BP [SBP/DBP], 129.8/79.5 mm Hg) who were treated for 16 weeks with once-daily testosterone gel treatment (starting dose, 40.5 mg/day; min, max dose, 20.25, 81.0 mg/day) to achieve testosterone concentration of 350-750 ng/dL. Main outcome measures included mean change in 24-h average SBP (primary endpoint) and DBP from baseline to week 16. The non-inferiority threshold was a two-sided 95% confidence interval (CI) upper limit <3.0 mm Hg for 24-h average SBP.

Results: Increase in mean ± SD serum testosterone concentration to a physiologic level (baseline, 244.4 ± 93.9 ng/dL; week 16, 502.5 ± 394.4 ng/dL) was associated with a 1.9-mm Hg mean change in 24-h average SBP observed in the primary analysis (baseline, 123.5 mm Hg; week 16, 125.4 mm Hg; 95% CI, 0.63-3.13 mm Hg; n = 169). As the upper CI limit modestly exceeded the non-inferiority margin (3 mm Hg), study drug effect on SBP could not be ruled out. Non-inferiority was observed in subgroups without hypertension or diabetes (95% CI, upper limit <3.0 mm Hg) and was not observed in those with hypertension or diabetes. Daytime SBP and DBP changes were larger compared with nighttime. No clear cardiovascular adverse events or new safety signals were identified.

Discussion and conclusions: While the effect of testosterone gel 1.62% on 24-h average SBP could not be ruled out based on the study's non-inferiority margin, the clinical relevance of the small-magnitude mean increase of 1.9 mm Hg is anticipated to be minimal considering the results of the TRAVERSE study of testosterone gel 1.62% and major adverse cardiac events.

Clinical trial information: ClinicalTrials.gov identifier: NCT04274894 (registered February 17, 2020).