A new generation of FDA-approved testosterone pills is reshaping testosterone replacement therapy (TRT), yet most U.S. patients continue using injections and topical gels. Oral testosterone undecanoate—available as Jatenzo (2019), Tlando (2022), and Kyzatrex (2022)—offers a needle-free, transferable-risk–free alternative, but has not displaced older delivery methods in clinical practice.
Irwin Goldstein, MD, director of San Diego Sexual Medicine, is among the clinicians who prefer the oral formulations. After using nearly every form of TRT over two decades, he now shifts most patients to pills. “All you have to do is swallow,” he says, calling the new orals “game changing.”
A Long Road Back for Testosterone Pills
Early oral testosterone, methyltestosterone, introduced in the 1930s, caused liver toxicity and left a lasting stigma around pill-based therapy. As a result, injections and topical products became standard practice for men with symptomatic low testosterone—typically defined as levels below 300 ng/dL with fatigue, low libido, and reduced energy.
Modern oral formulations avoid the liver entirely. They use testosterone undecanoate, which is absorbed through the lymphatic system rather than the liver, sidestepping the safety concerns that sidelined earlier pills.
How Pills, Injections, and Topicals Differ
All TRT forms raise circulating testosterone, but their pharmacologic profiles vary.
Pills: Taken twice daily, they provide steady hormone levels but require adherence. Oral formulations uniquely lower sex hormone-binding globulin (SHBG), increasing “free testosterone”—the biologically active form. Men with normal total testosterone but high SHBG may particularly benefit.
Injections: Intramuscular shots, typically given every 1–2 weeks, create rapid peaks and troughs in testosterone levels. A newer subcutaneous autoinjector, Xyosted, delivers smoother, more consistent levels.
Gels, patches, and pellets: Gels are applied daily but risk inadvertent transfer to others, including children. Patches avoid transfer but may irritate the skin. Implanted pellets release testosterone for roughly four months and appeal to patients seeking less frequent dosing.
“No one method is perfect,” says Stanton Honig, MD, chief of Reproductive and Sexual Medicine at Yale. “The orals are working well, but each option has its advantages.”
Evaluating Risks
Current evidence suggests oral TRT is not riskier than other delivery systems. Men pursuing fertility should avoid any form of TRT because exogenous testosterone suppresses sperm production; alternatives such as clomiphene citrate or human chorionic gonadotropin may boost testosterone while preserving fertility.
Cardiovascular concerns have also eased. In 2025, the FDA removed its boxed warning about heart-related risks after a large 2023 study found no increased rates of heart attack, stroke, or cardiovascular death among TRT users over roughly two years of follow-up.
A minority of patients experience mild increases in blood pressure. William B. White, MD, of the University of Connecticut, recommends monitoring blood pressure 4–6 weeks after initiating therapy, especially in men with hypertension.
Why Many Doctors Still Favor Older Options
Cost remains the major barrier to widespread adoption. While older gels and injectable testosterone cypionate are inexpensive generics, the newer oral products remain under patent and typically cost $150–$175 per month. Insurers often require patients to “fail” cheaper options before approving pills.
Limited marketing reach also slowed awareness. Smaller companies launched these products just before or during the COVID-19 pandemic, hampering physician-education efforts. One early manufacturer, Clarus Therapeutics, filed for bankruptcy in 2022.
Some patients and clinicians also prefer the dramatic testosterone peaks seen with injections, which can push levels above 800 or 1,000 ng/dL, even though symptom improvement—not numerical targets—drives clinical decision-making.
Choosing the Right Therapy
“The best form of testosterone is the one that fits the patient’s lifestyle, goals, and medical profile,” says Dr. Honig. He reviews the indications, risks, and costs of each delivery system and allows patients to select the option they can use consistently.
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