Testosterone Undecanoate

Mechanism of Action: Kyzatrex (oral testosterone undecanoate) is a prodrug absorbed via the lymphatic system and converted to testosterone, which binds androgen receptors to regulate gene expression for male secondary sexual traits, muscle, bone, libido, mood, and erythropoiesis.

Indications & Off-Label Uses: FDA-approved for adult male hypogonadism. Off-label use includes body composition improvement, performance enhancement, and “anti-aging,” though benefits and risks are uncertain.

FDA Status: Approved in 2022 as an oral testosterone replacement for hypogonadal men.

Clinical Evidence: Shown to restore serum testosterone to physiologic range, improving lean mass, sexual function, mood, bone density, and strength. Trials confirm efficacy without injections or gels. Evidence for use in eugonadal men is limited, and long-term safety (cardiovascular, prostate) remains under study.

Safety & Monitoring: Requires monitoring hematocrit, PSA, liver function, and lipids. Risks include polycythemia, hypertension, acne, fluid retention, gynecomastia, sleep apnea exacerbation, fertility suppression, and possible cardiovascular concerns. Oral dosing may cause GI side effects. Unlike older oral formulations, hepatotoxicity risk is low.