Oral testosterone undecanoate (Kyzatrex) is a capsule taken with food. It was approved by the FDA in 2022 for men with testosterone deficiency. The evidence is one six-month phase 3 study, reviewed by the FDA, and a separate blood-pressure study.
How it is taken
The FDA review lists the applicant's proposed dosing: a starting dose of 200 mg twice daily, taken in the morning and evening with food, with a minimum of 100 mg once in the morning and a maximum of 400 mg twice daily. Doses are adjusted to blood levels.
The pivotal study
The phase 3 study, MRS-TU-2019EXT, ran for six months. In the efficacy analysis of 139 men, 122 (87.8%) had average testosterone in the normal range at day 90. The FDA review gives the 95% confidence lower bound as 82.3% for that group, which is above the 65% bound the FDA required.
Among the 90-day completers, 96.1% reached normal levels, and the average exposure over the study was 452 ng/dL (Bernstein and Dhingra, 2024).
The peak-level criteria
The FDA also reviewed peak (Cmax) criteria. With all 155 men included, the Cmax targets were not met. After one site was excluded, because its plasma and serum samples disagreed, the targets were met: 87.7% of men stayed below 1,200 ng/dL (target above 85%), and 0% exceeded 2,000 ng/dL (target 0%).
This is why the approval depends on the exclusion. Readers should weigh it with that in mind.
Blood pressure
In a study of 155 men with hypogonadism (mean age 50.5 years), average 24-hour systolic pressure rose 1.7 mmHg at day 120 (95% CI 0.3 to 3.1). In men taking blood-pressure medicines the rise was 3.4 mmHg, against 0.7 mmHg in men not taking them (White et al., J Clin Hypertens 2021). Diastolic pressure and heart rate changed by less than 1 unit.
What this does not say
- The pivotal study had one treatment arm and no placebo. It cannot separate the drug's effect from what would have happened anyway.
- The study lasted six months. Outcomes beyond that, including heart, prostate, fertility and bone effects, are not established for this product.
- Averages describe the group. Each man's dose is set by his own blood levels, and the study does not predict his result.
How we use this
If oral testosterone is considered, we check blood pressure and testosterone levels during treatment, and we discuss fertility beforehand. We compare it with gels and injections for each man rather than assuming it is better or worse.
We do not promise outcomes from the single study. We use the data to explain what is known and what is not.
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- 1.Bernstein JS, Dhingra OP. A phase III, single-arm, 6-month trial of a wide-dose range oral testosterone undecanoate product. Ther Adv Urol 2024. Therapeutic Advances in Urology
- 2.FDA review, NDA 213953 (testosterone undecanoate, Kyzatrex), 2022. U.S. Food and Drug Administration
- 3.White WB, Bernstein JS, Rittmaster R, Dhingra O. Effects of the oral testosterone undecanoate Kyzatrex on ambulatory blood pressure in hypogonadal men. J Clin Hypertens 2021. Journal of Clinical Hypertension
- 4.Snyder PJ et al. Lessons from the Testosterone Trials. Endocr Rev 2018 (testosterone treatment increases the risk of erythrocytosis). Endocrine Reviews