Comparison of Intratesticular Testosterone between Men Receiving Nasal, Intramuscular, and Subcutaneous Pellet Testosterone Therapy: Evaluation of Data from Two Single-Center Randomized Clinical Trials.
Level 2 - randomized trial
Comparative analysis of data from two randomized clinical trials
PubMed 35791295 · doi:10.5534/wjmh.210261
What was done
Data were analyzed from two ongoing single-center, open-label randomized clinical trials comparing three testosterone replacement formulations in 75 symptomatic hypogonadal men (serum testosterone <300 ng/dL, median age 45 years). Interventions included subcutaneous testosterone pellets (TP, 800 mg), intranasal testosterone (NT, 11 mg three times daily), or intramuscular testosterone cypionate (TC, 200 mg every 2 weeks). Serum 17-hydroxyprogesterone (17-OHP, evaluated as a surrogate for intratesticular testosterone) and total serum testosterone were measured at baseline and follow-up.
What was found
Baseline median serum testosterone was 223.5 ng/dL and baseline 17-OHP was 46. At 4-month follow-up, 17-OHP suppression was significantly lower in the NT group (-33.3% from baseline) compared to the TP group (-44%) and the TC group (-65.3%) (p=0.005). Serum testosterone increased across all groups (p=0.005): TC (+157.6%), NT (+114.3%), and TP (+79.6%).
Why it matters
Short-acting nasal testosterone appears to preserve the intratesticular testosterone surrogate 17-OHP better than long-acting formulations. This suggests nasal delivery may offer a fertility-sparing alternative for hypogonadal men desiring to maintain spermatogenesis while on testosterone therapy.
Limits
The total sample size was small (n=75) and combined data across two separate open-label trials rather than a single direct three-arm trial. Intratesticular testosterone was not measured directly, and clinical fertility endpoints (sperm counts, semen analysis, or pregnancy rates) were not evaluated.
Cited by
- supports Intratesticular testosterone is the primary mediator of spermatogenesis in the testes.