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.
Key Findings
Results
Testosterone gel 1.62% treatment was associated with a mean 1.9 mm Hg increase in 24-hour average systolic blood pressure, which narrowly failed to meet the non-inferiority threshold.
Primary endpoint: mean change in 24-h average SBP from baseline to week 16 (n=169)
Baseline 24-h average SBP was 123.5 mm Hg; week 16 value was 125.4 mm Hg
95% CI for change was 0.63–3.13 mm Hg, with the upper limit modestly exceeding the pre-specified non-inferiority margin of 3.0 mm Hg
Non-inferiority threshold required the two-sided 95% CI upper limit to be <3.0 mm Hg
Study was a single-arm non-inferiority trial conducted at 36 US sites over 16 weeks
Results
Serum testosterone concentration increased from a hypogonadal baseline level to within the physiologic range following 16 weeks of treatment.
Baseline mean ± SD serum testosterone: 244.4 ± 93.9 ng/dL
Target testosterone concentration range was 350–750 ng/dL
Starting dose was 40.5 mg/day with allowable range of 20.25–81.0 mg/day
Results
Non-inferiority for 24-hour average SBP was demonstrated in subgroups without hypertension or diabetes but not in those with hypertension or diabetes.
Subgroups without hypertension or diabetes achieved 95% CI upper limit <3.0 mm Hg, meeting the non-inferiority criterion
Subgroups with hypertension or diabetes did not meet the non-inferiority criterion
These subgroup findings suggest differential BP responses based on cardiometabolic comorbidity status
Results
Daytime systolic and diastolic blood pressure changes were larger compared with nighttime blood pressure changes.
Both SBP and DBP showed greater increases during daytime hours than nighttime hours
This pattern was observed across the ambulatory blood pressure monitoring period
The differential day/night response was noted as a secondary finding in the ambulatory BP analysis
Results
No clear cardiovascular adverse events or new safety signals were identified during 16 weeks of testosterone gel 1.62% treatment.
246 men with hypogonadism were enrolled (mean age 57.6 years; mean office SBP/DBP 129.8/79.5 mm Hg)
Safety was assessed over 16 weeks of once-daily testosterone gel treatment
The authors referenced the TRAVERSE study of testosterone gel 1.62% and major adverse cardiac events as contextual support for the minimal clinical relevance of the observed BP increase
Methods
The study enrolled men with hypogonadism who had elevated mean office blood pressure at baseline, in the high-normal to stage 1 hypertension range.
Mean age of enrolled participants was 57.6 years
Mean office SBP at baseline was 129.8 mm Hg; mean office DBP was 79.5 mm Hg
Mean 24-h ambulatory SBP at baseline was 123.5 mm Hg, lower than office measurements
246 men were enrolled across 36 US sites; 169 were included in the primary analysis
Weber M, Aslam S, Efros M, Chan A, Khan N, Li X, et al.. (2025). Single-arm study of testosterone gel replacement therapy and ambulatory blood pressure outcomes in men with hypogonadism.. Andrology. https://doi.org/10.1111/andr.13779