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Last updated October 24, 2019. 8 minute read

Testosterone replacement therapy (TRT)

Testosterone replacement therapy aims to restore your testosterone to normal, healthy levels. Also called androgen replacement therapy, TRT can come in many different forms.

Dr Jefferson Chen Md Written by Dr. Jefferson Chen, MD
Reviewed by Dr. Mike Bohl, MD, MPH

You might have heard testosterone replacement therapy, or TRT, bandied about as a cure-all for the broadest of symptoms. “Tired? Stressed? Low sex drive? Moody? Ask your doctor about low-T!” The truth of testosterone is more complex than that, and there are real risks associated with testosterone replacement. It’s not a panacea for everything wrong in men’s health. Let’s learn all about testosterone replacement so that you don’t have to join the 7,000 men who sued pharma companies for not disclosing the risks of TRT (Elejalde-Ruiz, 2018).

Vitals

  • Vitamin K is a group of fat-soluble compounds.
  • Our bodies have vitamin K-dependent proteins that cannot do their jobs without the Ks.
  • These proteins are involved in vital functions, like blood clotting and bone metabolism.
  • MK-7, one form of vitamin K2, combats oxidative stress.
  • There are many food sources of the Ks: K1 comes mostly from green vegetables, while K2 is found mostly in animal products.

What is testosterone?

Testosterone is a sex hormone responsible for many functions across the body. It’s present in both men and women and contributes to muscle growth and development, bone health, libido (sex drive), maintaining red blood cell levels, and may play roles in improving mood and cognitive function. Testosterone gives males their characteristic traits: deeper voices, facial hair, penis and testicle development, and sperm production.

What happens if I have low testosterone/low-T?

Commonly, problems with low testosterone (or testosterone deficiency) crop up as males get older. One large study from the National Institutes of Health (NIH) reported that low testosterone affected 20% of men in their 60s, 30% of men in their 70s, and 50% of men over 80 (Harman, 2001). Males with low testosterone levels in adulthood experience decreased sex drive, erectile dysfunction (including decreased morning erections), fatigue, loss of muscle mass, increased fat gain, anemia (low blood cell count), and osteoporosis (weak bones). Before you jump out of your chair screaming, “That’s me!”, please keep in mind that a bunch of other health conditions can cause these symptoms, ranging from depression to iron deficiency. 

The FDA estimated that 1 in 5 men who received testosterone replacement never had their testosterone tested (FDA, 2018). To receive the benefits of testosterone replacement, you need to actually have low testosterone. Why expose yourself to all the risks without any upside? Testosterone is usually tested twice, early in the morning, when your levels are highest. Two low readings (<300 ng/dL), along with clinical symptoms, are usually required for a diagnosis. 

Your healthcare provider may also test your levels of follicle-stimulating hormone (FSH) and luteinizing hormone (LH), among others, to figure out whether or not another medical condition is causing your low testosterone. And some men with low-T will need special imaging tests so that your healthcare provider can get a full picture of what is going on. 

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What is TRT?

Once you’ve been diagnosed with hypogonadism or “low T,” your healthcare provider will be able to prescribe testosterone replacement therapy (TRT) for you. Testosterone replacement therapy aims to restore your testosterone to normal, healthy levels. Also called androgen replacement therapy, TRT can come in many different forms. 

How can you get TRT?

Here are the main ways to receive the testosterone used in TRT:

  • Topical: One way to get testosterone is through the skin. Gels (brand names AndroGel, Testim, and Fortesta), patches (brand name AndroDerm), and solutions (brand name Axiron) are all approved and available in the United States. The main advantage of receiving testosterone topically is that it is usually absorbed slowly, and levels in the blood are more stable. The disadvantages vary from product to product. Gels and solutions can have an unpleasant odor and could transfer to other people (including women or children) if touched after application. Patches can cause skin irritation and rashes. 
  • Injections: There are several injection formulations of testosterone available. Some of these are injected deep into the muscle, while others are injected just under the skin. Depending on the formulation, an injection lasts for a week to a couple of months before you have to go back to the doctor’s office to get it again. Other than the pain and inconvenience, the main drawback of injections is that the levels of testosterone fluctuate a lot, resulting in fluctuating mood, sex drive, and energy levels. Additionally, it’s more difficult for your healthcare provider to change your dose if it’s too high or too low. 
  • Buccal (cheek): A buccal testosterone system (brand name Striant) is also available. It’s a medication designed to stick to your gums. The main disadvantage is that it can irritate your gums and mouth. 
  • Pellets: Testosterone pellets (brand name Testopel) are plastic pellets that are placed implanted under the skin in the hips. There, they slowly release testosterone for 3 to 6 months. The main disadvantage here is the obvious need for implantation of the pellets in a healthcare provider’s office.
  • Oral tablets: Testosterone tablets (brand name Andriol, Restandol) are available but are usually not recommended by healthcare providers. There have been case reports of liver damage associated with long-term use (Westaby, 1977). Oral tablets also come with a warning about possibly causing high blood pressure and cardiovascular events (heart attacks or strokes).
  • Nasal gel: A new product is a nasal testosterone gel (brand name Natesto). You apply this gel to the inside of your nose. The advantage of the nasal gel is that the risk of transferring it to someone else is low, unlike other gels. The disadvantage is that you need to apply it three times a day in each nostril. Also, some people get runny noses, and nose bleeds. More concerning is that in mouse studies, the level of testosterone in the brain was twice as high with nasal testosterone as IV testosterone (Banks, 2009). Many healthcare providers are waiting for long term safety data to be available before recommending this to their patients. 

Most healthcare providers will typically suggest using topical gels first because they give you stable, normal levels of testosterone while being relatively easy to use and convenient. A study looking at patient satisfaction with TRT showed that there wasn’t a big difference between gels, injections, or pellets and that people were happy with any of those options (Kovac, 2014).

What are the benefits of TRT?

After taking TRT, what potential benefits can you expect to see? To answer this question, the National Institutes of Health (NIH) sponsored a series of coordinated trials to evaluate TRT, running for the course of a year. Testosterone treatment of 1 year for older men with low testosterone improved all aspects of sexual function.

So what did they come up with? They found that testosterone was helpful for mood and depressive symptoms, mild to moderate anemia and that it increased bone density and bone strength, and improved all measures of sexual function (Snyder, 2018). They also found that testosterone gave participants the ability to walk slightly further (a measure of exercise tolerance). Other, earlier studies have found that TRT can decrease body fat and increase lean muscle mass (Skinner, 2018) (Fui, 2016).

Notably, TRT did not improve energy or cognitive function.

Who shouldn’t get TRT?

Some men should not be prescribed TRT because the risks of therapy are too high. The Endocrine Society, a group of experts in this field, recommend against TRT in these men (Bhasin, 2018):

  • People with a history of prostate or breast cancer. Testosterone can theoretically cause prostate cancers to grow. Prostate cancer treatment is sometimes based on androgen deprivation, where testosterone is depleted from the body. Testosterone can also be converted to estradiol, which can theoretically cause breast cancers to grow.
  • People with a prostate node, PSA >4, or PSA >3 and a high risk for prostate cancer. Based on the same concept as above, testosterone can theoretically cause the prostate to grow, and people at high risk of prostate cancer should avoid taking TRT. 
  • People with severe lower urinary tract symptoms (LUTS). Lower urinary tract symptoms include frequently having urgent needs to urinate, feeling the need to urinate more often, producing less urine than usual, feeling pain or burning when urinating, difficulty starting to urinate, straining during urinating, having difficulty emptying your bladder, pain with ejaculation, discharge from the urethra, and discomfort in the genitals, groin, lower abdomen or lower back. These symptoms are frequently the result of having an enlarged prostate. Again, TRT can cause the prostate to grow, making these symptoms worse. 
  • People with severe and untreated sleep apnea. Testosterone can worsen obstructive sleep apnea. If your sleep apnea is treated, you can get TRT. 
  • People with erythrocytosis, a condition where you have too many red blood cells. Testosterone can encourage more red blood cells to be produced. If you have too many red blood cells, your risk of having a blood clot is increased.
  • People with thrombophilia, a condition where you’re at higher risk for blood clots. Testosterone can possibly further increase your risk of blood clots.
  • People with uncontrolled heart failure. Testosterone can cause more fluid to be retained in your body and can worsen heart failure. 
  • People with a recent heart attack or stroke in the last six months. Testosterone has possible cardiovascular risks, including risks of heart attacks or strokes. 
  • People who want to have a child in the near term. TRT suppresses spermatogenesis, the process of creating new sperm, which can cause you to lose your fertility. 

What are some potential risks and side effects of testosterone therapy?

Receiving TRT is not risk-free. Its side effects mirror the reasons why certain people shouldn’t get testosterone listed above. TRT can cause infertility and can shrink your testicles. It can cause acne and oily skin, increases in breast size, and calcification of your blood vessels. There is a theoretical increased risk of prostate cancer, and benign prostatic hyperplasia (BPH) as testosterone can drive prostate growth and increased prostate-specific antigen (PSA). Clinical trials haven’t proved this, but it’s possible that longer-term studies would show this effect. Other theoretical risks include cardiovascular problems, including heart attacks or strokes, but this has yet to be definitively proven in clinical trials (Fernández-Balsells, 2010).

Importantly, TRT also suppresses your body’s ability to make testosterone, which can make you feel worse if you stop taking TRT.