Testosterone Replacement Therapy Overview

Testosterone replacement therapy (TRT), sometimes called androgen replacement therapy. TRT is primarily used to treat low testosterone (T) levels, which can occur with age or as a result of a medical condition.

But it’s becoming increasingly popular for non-medical uses, including:

  • Achieving higher energy levels
  • Building muscle mass for bodybuilding 
  • Enhancing sexual performance

Some research suggests that TRT may in fact help you achieve some of these goals. But there are some caveats. Let’s dive into what exactly happens to your T levels as you get older and what you can realistically expect from TRT.

TRT, or androgen replacement therapy (ART), is a treatment that doctors give to males with testosterone deficiency who show symptoms of hypogonadism.

Taking prescription testosterone helps restore the levels of this hormone in the blood, reversing the symptoms of low testosterone. Individuals who take testosterone may notice improvements in alertness, sexual function, energy, mood, and overall well-being.

Reasons for Decline of Testosterone with Age

Your body naturally produces less T as you age. According to an article in American Family Physician, the average male’s T production goes down by about 1 to 2 percent each year.

This is all part of a completely natural process that starts in your late 20s or early 30s:

  1. As you age, your testicles produce less testosterone.
  2. Lowered testicular T causes your hypothalamus to produce less gonadotropin-releasing hormone (GnRH). .
  3. Reduced GnRH causes your pituitary glad to makes less luteinizing hormone (LH).
  4. Lowered LH results in lowered overall testosterone production.

This gradual decrease in T often doesn’t cause any noticeable symptoms. A significant drop in testosterone levels may cause:

  • Fewer spontaneous erections
  • Erectile dysfunction
  • Low sex drive
  • Lowered sperm count or volume
  • Trouble sleeping
  • Unusual loss of muscle and bone density
  • Unexplained weight gain


Diagnosis of Low Testosterone

The only way to know whether you truly have low T is by seeing a healthcare provider for a testosterone level test. This is a simple blood test, and most providers require it before prescribing testosterone replacement therapy (TRT).

You may need to do the test several times because testosterone levels are affected by various factors, such as:

  • Certain medications, like anticonvulsants and steroids
  • Diet
  • Level of fitness
  • Time of day the test is done

Here’s the breakdown of typical testosterone levels  for adult males starting at age 20:

Age (in years) T levels in nanograms per milliliter (ng/ml)
20–25 5.25–20.7
25–30 5.05–19.8
30–35 4.85–19.0
35–40 4.65–18.1
40–45 4.46–17.1
45–50 4.26–16.4
50–55 4.06–15.6
55–60 3.87–14.7
60–65 3.67–13.9
65–70 3.47–13.0
70–75 3.28–12.2
75–80 3.08–11.3
80–85 2.88–10.5
85–90 2.69–9.61
90–95 2.49–8.76
95–100+ 2.29–7.91

If your testosterone levels are only slightly low for your age, you probably don’t need TRT. If the testosterone levels significantly low, your provider will likely do some additional testing before recommending TRT.

Types of Testosterone Replacement Therapy

There are several ways to administer testosterone:

Injectable

Injectable testosterone is an inexpensive and common form of TRT. A person can receive short-acting treatment, which involves a shot every 1 or 2 weeks, or long-acting treatment, in which the second shot is 4 weeks after the first, and all others are 10 weeks apart. The dosage and frequency of the treatment may vary depending on the person.

Doctors inject short-acting testosterone under the skin or into the muscle, while long-acting shots go in the gluteal muscles.

TRT can cause fluctuations in testosterone levels, which can affect energy levels, libido, mood, and the presence of symptoms such as breast tenderness.

Topical (Transdermal)

People usually apply gels and creams on a daily basis. Gradual absorption causes more stable testosterone levels in the blood.

However, people using topical treatments must be careful to avoid skin-on-skin contact with other people for at least 6 hours after application. It is important to prevent the risk of transferring the medication onto other people’s skin because it may be dangerous for pregnant people and children.

Topical patches stick to the skin and stay in place for 24 hours until the next dose. They typically come in doses of between 2 milligrams (mg) and 5 mg. The downsides to patches are that they are not cosmetically appealing and often cause skin irritations. In comparison with oral medications, topical patches may prove less toxic to the liver.

Topical gel dosage is usually between 40–100 mg per day but this will vary between products. A person should start at the lowest recommended dose and increase gradually, if necessary.

Cheek or Buccal Patches

A person places a buccal patch above the upper teeth, and it releases testosterone over 12 hours. These patches usually contain 30 mg. A person should apply them twice each day, around 12 hours apart. However, they can cause headaches and gum and mouth irritation.

Testosterone Implants or Pellets

Testosterone pellets are small plastic pellets that doctors implant under the skin. The implant goes into a person’s upper hip or buttock. The pellets dissolve slowly and can deliver TRT for 3–6 months. The dosage varies between individuals and a person should discuss this with their doctor prior to the first implantation.

Inserting implants is a minor inpatient surgical procedure. A doctor makes a small incision in the fatty tissue below the skin to insert the pellets. They perform the procedure under local anesthesia.

Oral Testosterone

Oral testosterone is a less common type of TRT that is more expensive and less practical. Its long-term use can potentially cause liver damage.

Most tablets also come with warnings about the drug causing hypertension and stroke. As a result, only individuals who cannot use other forms of TRT resort to taking testosterone by mouth.

A doctor will recommend a dosage ranging from 225–396 mg, and a person will typically take oral testosterone tablets twice daily.

Intranasal

A person applies nasal testosterone gel to the inside of the nose. They will need to do this three times a day at intervals of 6–8 hours, preferably at the same times every day. The dosage is usually 11 mg per application across both nostrils, resulting in a total dosage of 33 mg daily.

Some common reactions to this treatment include headaches, nosebleeds, a runny nose, and nasal discomfort.

Administration of Testosterone Replacement Therapy

There are several ways to do TRT. Your best option will depend on your medical needs as well as your lifestyle. Some methods require daily administration, while others only need to be done on a monthly basis.

TRT methods include:

  • Intramusculare injections
  • Oral medications
  • Transdermal patches
  • Topical creams

There’s also a form of TRT that involves rubbing testosterone on your gums twice daily.

Medical Uses of Testosterone Replacement Therapy

TRT is traditionally used to treat hypogonadism, which occurs when your testes (also called gonads) don’t produce enough testosterone.

There are two types of hypogonadism:

  • Primary hypogonadism. Low T results from issues with your gonads. They’re getting signals from your brain to make T but can’t produce them.
  • Central (secondary) hypogonadism. Low T results from issues in your hypothalamus or pituitary gland.

TRT works to make up for T that isn’t being produced by your testes.

If you have true hypogonadism, TRT can:

  • improve your sexual function
  • boost your sperm count and volume
  • increase levels of other hormones that interact with T, including prolactin

TRT can also help to balance unusual T levels caused by:

  • Autoimmune conditions
  • genetic disorders
  • infections that damage your sex organs
  • undescended testicles
  • radiation therapy for cancer
  • sex organ surgeries

Non Medical Uses of Testosterone Replacement Therapy

Many countries, including the United States, don’t allow people to legally purchase T supplements for TRT without a prescription.

Still, people seek out TRT for a range of non-medical reasons, such as:

  • Boosting sexual drive or performance 
  • Gaining extra muscle mass for body building
  • Increasing energy levels
  • Loosing weight
  • Raising endurance for athletic activities

TRT has indeed been shown to have some of these benefits. For example, a recent review concluded that it effectively increased muscle strength in middle-aged and older males.

But TRT has few proven benefits for people, especially younger males, with normal or high T levels. And the risks may outweigh the benefits. A small 2014 study found a link between high T levels and low sperm production.

Plus, using TRT to gain a competitive edge in a sport is considered “doping” by many professional organizations, and most consider it grounds for termination from the sport.

Costs of Testosterone Replacement Therapy

The costs of TRT varies based on what type you’re prescribed. If you have health insurance and need TRT to treat a health condition, you likely won’t pay the full cost. The actual cost may also vary based on your location and whether there’s a generic version available.

Generally, you can expect to pay anywhere from $20 to $1,000 per month. The actual cost depends on a range of factors, including:

  • Administration method
  • Type of medication
  • Whether there’s a generic version available
  • Your location

When considering the cost, keep in mind that TRT simply boosts your T levels. It won’t treat the underlying cause of your low T, so you may need life-long treatment.

Risks of Testosterone Replacement Therapy

Experts are still trying to fully understand the risks and side effects of TRT. According to Harvard Health, many existing studies have limitations, such as being small in size or using larger-than-usual doses of T.

As a result, there’s still some debate over the benefits and risks linked to TRT. For example, it’s been said to both increase and decrease the risk of certain types of cancer.

A 2016 article in the journal Therapeutic Advances in Urology suggests that some of these conflicting views are the result of overzealous media coverage, especially in the United States.

Before trying TRT, it’s important to sit down with your healthcare provider and go over all the potential side effects and risks. These may include:

  • Acne or similar skin breakouts
  • Benign prostatic hyperplasia (enlarged prostate)
  • Chest pain
  • Deep vein thrombosis
  • Difficulty breathing
  • Heart attack
  • Speech difficulties
  • Low sperm count
  • Polycythemia vera
  • Lowered HDL (“good”) cholesterol
  • Swelling in the hands or legs
  • Stroke
  • Sleep apnea
  • Pulmonary embolism

    You shouldn’t undergo TRT if you’re already at risk for any of the conditions listed above.


Benefits of Testosterone Replacement Therapy

According to a 2019 study, testosterone replacement therapy (TRT) can improve sexual function, including:

  • Libido
  • Symptoms of erectile dysfunction
  • Sexual satisfaction

Further 2019 research suggests that testosterone replacement therapy (TRT) can also maintain bone density, with a 2022 study also revealing that TRTs may improve cognitive function and attention span.

However, these benefits were quite modest and went away with the discontinuation of TRT. Around half of the participants in the 2019 study still had bone mineral density in the ranges of osteopenia or osteoporosis while on TRT.

Side Effects of Testosterone Replacement Therapy

The Food and Drug Administration (FDA) explains that the benefits and safety of TRT for treating low testosterone levels due to aging are not known. The organization requires that testosterone products carry warnings mentioning the possible risk of stroke and heart disease.

A 2019 review found that males undergoing TRT may have a higher risk for cardiovascular events such as stroke. However, further research will help to confirm this.

Other side effects of taking testosterone include:

  • Acne, rashes and itching
  • Anxiety 
  • Anger and aggressive behavior 
  • Breast soreness or enlargement (Gynecomastia)
  • Bladder irritability
  • Decreased sperm production
  • Deep vein thrombosis
  • High blood pressure (hypertension)
  • Hair loss or excessive hair growth 
  • High red blood cell count, which may lead to blood clots
  • Increase prostate size
  • Liver dysfunction
  • Male pattern baldness
  • Priapism
  • Shrinkage of testes
  • Worsening of prostate cancer

High cholesterol may also be a side effect. However, a 2021 study suggests that TRT may improve total cholesterol levels.

The current scientific literature suggests that TRT worsens breast and prostate cancer. However, TRT may offer benefits to people with early-stage prostate cancer without stimulating the recurrence or progression of cancer.

Summary

TRT has long been a treatment option for people with hypogonadism or conditions associated with reduced T production. But its benefits for those without an underlying condition aren’t as clear, despite all the hype.

Talk to your doctor before you take any T supplements or medications. They can help you determine whether your goals with TRT are safe and realistic.

It’s also important to be monitored by a medical professional as you take T supplements to note any unwanted symptoms or side effects that may occur during treatment.

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