Is Testosterone Replacement Therapy (TRT) Safe? Side Effects and Risks Reviewed

If you’ve been prescribed testosterone recently, many people are right there with you. In the U.S., more and more prescriptions for testosterone replacement therapy (TRT) have been issued in recent years. TRT — sometimes called a testosterone supplement — can be used to boost the amount of testosterone in your body. 

TRT is a helpful option for many people, primarily men with low testosterone levels and symptoms of deficiency. But no matter if you’re just starting testosterone or have been taking TRT for some time, it's important to be aware of the potential risks of your treatment. 

Here, we’ll discuss the potential risks and side effects of TRT. 

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What is testosterone replacement therapy used for?

As we get older, our body's natural supply of certain hormones can go down. TRT may be given to people when testosterone levels become too low. This is similar to when estrogen therapy is given to women with symptoms of menopause.

A blood test can tell you when testosterone levels get too low. But symptoms tend to appear when your body’s testosterone levels drop below 300 ng/dL. You might have low testosterone levels if you experience one or more of the following symptoms: 

• Lower sex drive than normal

• Fewer morning erections

• Loss of body hair

• Low bone mineral density

• Gynecomastia

• Smaller testes

• Erectile dysfunction

Forms of TRT

You can take testosterone in several ways. You and your healthcare provider may choose one option over another based on your preferences, treatment goals, and insurance coverage status. Available options include: 

• Injections

• Oral pills

• Gels that you place on your skin

• Gels that you put in your nose 

• Patches that you place on your skin

• Pellets that are placed under your skin

What are common TRT side effects?

Like with most other medications, TRT can cause side effects. But the specific side effects that you experience will depend on the type of testosterone that you’re taking. Each kind of testosterone is more likely to cause certain side effects than others.

This isn’t an exhaustive list, but here are some of the most common considerations to keep in mind.

Are there any serious risks with testosterone replacement therapy?

Yes. More serious risks are also possible. Heart-related (cardiovascular) risks are a common concern, but other risks are also important to know about. 

Heart risks

In 2015, the FDA released a statement saying that only people with low testosterone levels due to hypogonadism should use TRT. Hypogonadism is when your body doesn’t make enough testosterone because of a problem with your pituitary gland, brain, or testicles. In their statement, the FDA mentioned that men taking TRT for low testosterone due to aging (rather than hypogonadism) have a higher risk of heart-related problems. These include heart attack, stroke, and different types of blood clots.

The FDA was prompted to release this statement based on a variety of data, including a 2013 study. In this study, researchers found that certain men taking TRT were associated with a 30% higher risk of heart attack, stroke, or death than men who weren’t taking TRT. 

In another study, researchers found that men ages 65 and older were associated with a two-fold risk of having a heart attack. Additionally, men taking TRT who were younger than 65 — but had a heart condition — were at almost a three-fold risk of having a heart attack. 

Changes in red blood cell levels

Testosterone has many jobs in your body. One of them is helping to create red blood cells. 

For the most part, TRT shouldn’t cause a significant jump in your red blood cell levels. But in some cases, TRT can make your red blood cell count too high. 

There’s a theoretical risk that this could lead to a higher risk of blood clots and heart attacks. But it’s important to note that higher red blood cell levels caused by TRT haven’t led to significantly more heart attacks or blood clots in clinical studies. 

Prostate cancer and BPH

There’s been a long-standing, hypothetical connection between TRT and prostate cancer. In the 1940s, researchers discovered a link between testosterone levels and prostate cancer in men. For a long time, experts believed that taking TRT raises a man’s risk of developing prostate cancer.

However, a newer meta analysis didn’t show a higher risk of prostate cancer in men who use TRT. PSA levels can go up after starting TRT, but it isn’t thought to lead to a higher risk of developing prostate cancer.

Plus, if you have undergone treatment for prostate cancer, you may still be able to take TRT. One study found that people who recovered from prostate cancer and were taking TRT didn’t have a higher chance of their cancer coming back. If this is your situation, you and your healthcare provider can discuss if TRT is appropriate for you. 

Prostate cancer aside, TRT may worsen symptoms of benign prostate hyperplasia (BPH). If you have BPH, make sure to let your provider know if there are any changes in your symptoms after starting TRT.

What is the safest testosterone product?

There’s not necessarily one form of testosterone that’s considered the safest. Every TRT product may have different side effects and risks based on how it’s administered, as discussed above. But there are certain situations where you may have a higher risk of serious health problems from TRT in general.

Who shouldn’t take testosterone?

Testosterone isn’t safe for everyone. Due to the potential for serious side effects, some people shouldn't use TRT at all. The following situations are testosterone contraindications, or reasons that make it unsafe to take TRT:

• Uncontrolled heart failure

• Having a previous heart condition

• Actively trying to father a child

• Active prostate or breast cancer

• Uncontrolled obstructive sleep apnea

• Liver failure 

• Polycythemia vera

When should I talk to a healthcare provider about side effects from TRT?

If you’re experiencing any side effects from TRT, it’s a safe bet to contact the healthcare provider who prescribed the medicine to you. They can walk you through potential ways to prevent or manage them. And depending on your symptoms, they may also decide to switch which form of TRT you’re using. For example, if you’re having significant pain from TRT injections, they may switch you to a topical gel or patch. 

If you’re experiencing side effects that feel severe, seek medical care immediately. You should also seek emergency treatment if you feel like you’re experiencing symptoms of a heart attack or stroke. Symptoms of a heart attack include chest pain, difficulty breathing, or feeling weak or lightheaded. Signs that you may be having a stroke include sudden weakness or numbness in the face, arm, or leg (especially on one side of the body), trouble seeing, or sudden confusion or coordination issues.

Why trust our experts?

Written by:

Austin Ulrich, PharmD, BCACP

Austin Ulrich, PharmD, BCACP, is a board-certified ambulatory care clinical pharmacist. In his early career, he provided direct patient care in a variety of settings, including hospital and community pharmacies, and in a primary care clinic as a clinical pharmacist.

Edited by:

Joshua Murdock, PharmD, BCBBS

Joshua Murdock, PharmD, BCBBS, is a licensed pharmacist in Arizona, Colorado, and Rhode Island. He has worked in the pharmacy industry for more than 10 years and currently serves as a pharmacy editor for GoodRx.

Reviewed by:

Sanjai Sinha, MD

Sanjai Sinha, MD, is a board-certified physician with over 20 years of experience. He specializes in internal medicine.

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