Search IconSearch
February 27, 2024/Urology & Nephrology/Urology

Oral Medication Offers New Option for Testosterone Replacement

Unlike earlier pills, new drugs do not cause liver toxicity

Man examining prescription bottle in kitchen

For patients with testosterone deficiency, intramuscular injection and topical gel have been first-line therapies for decades. Now, a new generation of medications has made oral testosterone a safe option as well.


Cleveland Clinic is a non-profit academic medical center. Advertising on our site helps support our mission. We do not endorse non-Cleveland Clinic products or services. Policy

While cost and lack of insurance coverage present a barrier for some patients, the new oral drugs could be good alternatives for people who have contraindications to other treatments. There are early indications that the oral drugs cause fewer side effects than injections and other long-lasting forms of testosterone replacement therapy, says urologist Petar Bajic, MD, Director of the Center for Men’s Health at Cleveland Clinic.

“Testosterone deficiency is one of the only conditions for which first-line treatment is not a pill,” he says. “But most patients prefer oral medication, and these newer drugs provide that option.”

An older type of oral testosterone was prescribed to patients in the 1980s but fell out of favor because of liver toxicity, he notes. The three new drugs, Jatenzo®, Tlando® and Kyzatrex™, avoid that problem because they bypass the liver to be metabolized through the lymphatic system.

“These new drugs are not dangerous to the liver,” stresses Dr. Bajic.

All three drugs must be taken with food to be effective, he notes. Jatenzo and Tlando should be taken with a meal to ensure proper absorption.

Upside and downside

The current first-line therapies for testosterone replacement have some significant downsides. Intramuscular injection can be painful, and topical treatments carry the risk of transference to the patient’s partner or children. Pellet implantation, another treatment option, also can cause pain.

In addition, these therapies seem to have a higher risk of side effects including erythrocytosis, possibly because they are delivered at higher doses and designed to be long-lasting.

“Patients who have tried other forms of testosterone and had a rise in their blood count, particularly with high-duration therapies like injections or testosterone pellets, might see less of that side effect with a shorter-acting oral testosterone,” says Dr. Bajic.

On the other hand, oral testosterone may not be right for all patients, adds urologist Neel Parekh, MD, a male infertility and men’s health specialist at Cleveland Clinic. For example, patients who don’t eat breakfast may not have adequate absorption with certain formulations, and patients who do not already take twice-daily medication may forget to take a dose.

Making oral drugs more affordable

According to Drs. Bajic and Parekh, testosterone replacement therapy should be used for patients who are experiencing symptoms of testosterone deficiency, not to boost testosterone in patients with normal levels.

While most insurance plans don’t cover oral testosterone as a first-line treatment, patients do have some options to make the oral medication more affordable.

For example, insurance coverage may be approved if the patient is not able to use other forms of testosterone replacement therapy or has tried other therapies and experienced side effects.


“If a patient is, let’s say, afraid of needles and not able to have injection therapy, and maybe they have small children and are worried about transferring the topical treatment to their kids, then sometimes that justifies insurance coverage,” says Dr. Bajic.

For patients without insurance coverage, all three medications are available as cash-pay options at specialty pharmacies. Some manufacturers offer rebates to help reduce out-of-pocket costs.

Helping patients choose the right treatment

Physicians prescribing testosterone replacement therapy should counsel patients about different options and help them choose the best treatment for them.

“Educating patients about the benefits, risks and proper administration of testosterone replacement therapy is essential for promoting treatment adherence and ensuring patient safety,” says Dr. Parekh. “While the newer generation of oral testosterone does not cause liver toxicity, monitoring patients’ lab work and symptoms in accordance with American Urological Association guidelines is necessary to ensure safe and effective treatment.”


Related Articles

Urologist talking with patient
1-Minute Consult: Does My Patient Have Testosterone Deficiency?

Testosterone deficiency can prove challenging to diagnose and treat

x-ray of bone fracture in a forearm
TRAVERSE Substudy Links Testosterone Therapy to Increased Fracture Risk in Older Men With Hypogonadism

Surprise findings argue for caution about testosterone use in men at risk for fracture

UTI bacteria and artificial intelligence
AI Algorithms Accurately Predict Antibiotic Resistance in UTI

Up to 3 days faster than waiting for urine culture results

Enlarged prostate
Benign Prostatic Hyperplasia: Alternatives to Transurethral Resection

Review the advantages and disadvantages of newer interventions

Drawing of surgeon's fingers pressing into a patient's body
Low Anterior Access Enhances Outcomes in Single-Port Robotic Urologic Surgeries

Pioneering and refining the approach in pyeloplasty, nephrectomy and more

URL_Pavelko_3777858_Urology_Dr. Lundy in Clinic_04-26-23_LDJ
January 30, 2024/Urology & Nephrology/Urology
Starting the Conversation About Male Infertility

Male factors play a role in about half of all infertility cases, yet men often are not evaluated

URL_Mould_3793308_Dr. Hadley Wood with patient at Q8_04-07-23_LD
December 1, 2023/Urology & Nephrology/Urology
Cleveland Clinic Urologist To Lead Esteemed Medical Journal

Hadley Wood, MD, shares her vision as the new editor-in-chief of Urology