Oral testosterone undecanoate significantly improved serum testosterone levels and sexual activity among men with hypogonadism, according to a subanalysis of the inTUne phase 3 trial presented at the Androgen Society annual meeting. The findings provide crucial efficacy data for oral testosterone therapy, which has emerged as a new treatment option in the United States after more than 60 years without FDA-approved oral formulations.
Trial Design and Patient Population
The inTUne phase 3 trial enrolled 222 men with hypogonadism to assess the safety and efficacy of oral testosterone undecanoate (Jatenzo, Tolmar) compared with topical testosterone. Participants were randomly assigned 3:1 to receive twice-daily Jatenzo (n = 166) or once-daily topical testosterone (n = 56) for 105 days.
"In the United States, oral testosterone is a relatively new phenomenon," said Mohit Khera, MD, MBA, MPH, the F. Brantley Scott Chair in Urology and director of the Laboratory for Andrology Research at Baylor College of Medicine. "While we have very good data on oral testosterone undecanoate injectables, we have very little data on oral testosterone undecanoate in terms of sexual function."
Testosterone Level Achievements
Among 154 men who received Jatenzo and had complete serum testosterone data, the therapy demonstrated robust efficacy in normalizing testosterone levels. At day 21, 93% of participants achieved serum testosterone levels of 300 ng/dL or higher, with this proportion increasing to 99% by day 105.
More notably, 68% of men reached the higher threshold of 450 ng/dL or greater at day 21, with 92% achieving this level by day 105. Testosterone levels were measured 4 hours post-dose at days 21, 56, and 105 throughout the study period.
Sexual Function Improvements
The study utilized the Psychosexual Daily Questionnaire-4 (PDQ-4) to assess sexual function at baseline and day 105, analyzing eight individual domains including sexual desire, pleasure, erection quality, and mood parameters.
Mean sexual activity scores increased from 2.43 points at baseline to 4.28 points at day 105, representing a 1.85-point improvement. "Just to put this in perspective, when we look at the TRAVERSE trial, that change [in sexual activity score] was about 1 [point]," Khera noted. "This is significantly higher."
Comprehensive Sexual Health Benefits
All individual sexual activity domains showed significant improvements during the 105-day treatment period. Participants experienced a 1.7-point increase in sexual desire and a 1.13-point rise in highest sexual pleasure without a partner. Sexual pleasure with a partner improved by 1.1 points, while the ability to maintain an erection increased by 1.32 points.
Mood-related parameters also improved, with positive mood scores rising by 0.62 points and negative mood decreasing by 0.52 points, indicating fewer negative mood symptoms. The percentage of time participants experienced full erections improved significantly from 59% at baseline to 74% at day 105.
Comparative Treatment Outcomes
Men receiving topical testosterone in the study demonstrated similar improvements across all eight PDQ domains as those receiving oral testosterone undecanoate, suggesting comparable efficacy between the two formulations for sexual function parameters.
The FDA approved Jatenzo in March 2019 as the first oral testosterone to receive approval in more than 60 years. Since then, additional oral testosterone products have entered the market, including Tlando (Verity Pharmaceuticals) and Kyzatrex (Marius Pharmaceuticals), both approved in 2022.
