An Overview of Testosterone Replacement Therapy

There can be a lot of confusion when it comes to hormone therapy. For example, with testosterone replacement therapy, there are a lot of important questions to answer. When is it necessary? Is it safe? What are the risks, and perhaps more importantly, can the benefits outweigh the potential side effects?

There are a variety of reasons why testosterone replacement therapy might be implemented on a patient. However, this hormone therapy isn't for everyone.

man and woman lie in bed, the woman is asleep the man is awake and thinking.
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What Is Testosterone?

Testosterone is considered a male sex hormone, and it is primarily produced in the testicles (although a very small amount comes from the adrenal glands).  Testosterone is responsible for the development of primary sexual characteristics: male genitalia. It is also responsible for secondary sexual characteristics including muscle bulk, deep voice, and hair pattern.

Testosterone helps regulate other physical factors that impact mood and energy levels and protect heart health. It is also responsible for maintaining a normal sex drive. Testosterone helps to influence or provides:

  • Cardiovascular protection
  • Red blood cell production
  • Mood and overall sense of well being
  • Vitality (energy level)
  • Bone density and strength
  • Sperm production

Conditions That Cause Low Testosterone

There are a number of conditions that could cause low testosterone levels, which include:

  • Primary hypogonadism (when testes do not properly function)
  • Secondary hypogonadism (when production of testosterone suppressed due to a tumor of the pituitary gland or hypothalamus)
  • Cancer (testicular, prostate, or male breast cancer)
  • Bilateral orchidectomy (removal of both testicles due to cancer or other conditions such as testicular torsion)
  • Injuries to the testicles
  • Delayed puberty
  • The normal aging process

Testosterone Replacement Therapy (TRT)

Testosterone replacement therapy is the process of replacing the testosterone that is lost as a result of an injury, a condition that is present at birth, or a disease that causes low testosterone levels. It can also be given to replace testosterone levels that have fallen as a result of an orchiectomy (removal of one or both testicles).


There are various options for the administration of TRT.

Patches (Transdermal)

The body is able to absorb testosterone through patches, which are easy to use. However, they may cause skin irritation and must be applied multiple times each day. Furthermore, not all patients absorb this medication well.

Topical Gels

These are convenient to apply, but precautions must be taken to make sure that the skin that has been exposed to the TRT gel does not inadvertently rub off on other body parts. Women and children should not be exposed to these gels.

Buccal Patch

This type of patch, which is not commonly used, is placed on the gums two times per day. It is convenient to use but may cause gum irritation.


Intramuscular njections are given every two to 10 weeks (depending on the prescribing physician). Injections are often the least expensive option, and provide more significant increase in testosterone levels with the greatest symptom improvement.


This method involves pellets that are placed under the skin every three to six months. Once they are administered, the pellets require the least amount of maintenance and a high level of continuous steady dosing. However, they do require minor surgery each time a new dosage is due. Further, pellets can extrude, and as with any procedure there is inconvenience and small risk of infection.


Jatenzo (testosterone undecanoate) capsules are a newer oral medication. Capsules are convenient and, unlike some previous oral testosterone formulations, not thought to cause liver damage.


Natesto is the first FDA-approved intranasal testosterone therapy. Typically, it is administered three times a day per nostril.

It is important for men interested in future fertility not to receive standard testostosterone replacement therapy since this can lead to low or no sperm count and infertility issues. If a man with low testosterone is interested in future fertility, he should seek counseling with a urologist focusing on male reproduction for alternative options.

What Is Hypogonadism?

Male hypogonadism is a condition in which the testicles do not produce enough testosterone, do not produce sperm or both. According to one study, 20% of men over age 60, 30% of men over age 70, and 50% of men over age 80 have hypogonadism. A man may be born with hypogonadism, or it may develop later in life. Testosterone declines by 1% per year, 10% per decade starting at age 30 years in all men.

Common symptoms of hypogonadism
Illustration by JR Bee, Verywell.


Symptoms of hypogonadism in adult males may include:

  • Erectile dysfunction
  • Infertility
  • Difficulty concentrating
  • Fatigue
  • A decrease in body and facial hair growth
  • A decrease in muscle mass
  • Development of breast tissue (gynecomastia)
  • Loss of bone mass (osteoporosis)

TRT for Hypogonadism

Testosterone replacement therapy is a common treatment option for men with low testosterone levels and symptoms of hypogonadism. TRT can produce very positive results and even cause a person to regain masculine qualities that were lost due to low testosterone production. 

Use of TRT for those with hypogonadism has been shown to be effective and generally safe, but additional clinical research data is needed to fully establish long-term safety.


TRT may not be recommended when a person has conditions such as:

  • Prostate cancer (but one may become a candidate after completion of successful treatment)
  • Male breast cancer
  • Sleep apnea
  • Urinary tract symptoms (such as urinary urgency or frequency, linked with an enlarged prostate)
  • Congestive heart failure or other cardiac issues
  • High red blood cell count
  • Low testosterone caused by aging

Testosterone and Aging

Testosterone levels naturally decrease as a man ages, starting at around age 30, and continue to decline throughout life.

Although TRT has become a popular treatment, many experts do not recommend TRT for age-related symptoms of low testosterone.

A primary reason is due to the many side effects of long-term testosterone replacement therapy, including a controversial increased risk of heart disease. While some studies support this, more have shown that there may not be detrimental effects of TRT on heart health. 

Another factor that poses a controversial issue in prescribing TRT to aging healthy men is that once a person begins to take it, the body will stop making testosterone. This makes a person dependent on taking the hormone replacement long-term.

Symptoms of Age-Related Low Testosterone

Due to aging, testosterone levels naturally decrease. There are several normal changes that may occur, including insomnia (or other sleep disturbances), low sex drive, an increase in body fat, a reduction in muscle mass, a decrease in motivation, and a low level of self-confidence.

Side Effects of TRT

Short term side effects of testosterone replacement therapy may include:

  • Acne or oily skin
  • Swelling or tenderness of breasts
  • Swelling of the ankles (fluid retention)
  • A decrease in the stream or frequency of urination
  • High blood cell counts (which could increase the risk of blood clots)
  • Sleep apnea or worsening of sleep apnea (difficulty breathing during sleep)
  • Shrinkage of the testicles
  • Hair loss
  • Mood swings
  • Increased aggression and irritability
  • Changes in cholesterol levels
  • Reduction in sperm count (which may adversely impact fertility)

Long term TRT side effects are known to be more problematic, including the possible risk of:

  • Cardiovascular problems (stroke and heart attack)
  • Increased risk of death from a heart attack
  • Polycythemia (an increased concentration of hemoglobin levels from a rise in red blood cells)
  • Worsening of urinary symptoms
  • Hip fracture (from osteoporosis)

Important Tests

There are some important recommendations that those receiving TRT should follow as precautionary measures. One should have baseline bone density testing (DEXA) and regular bone density tests (to rule out osteoepenia or osteoporosis). Regular lab tests to check testosterone levels, PSA (marker of prostate health/cancer), hematocrit, and sometimes liver enzymes are also important and should be done routinely while taking TRT.

In addition, it is important to get a physical exam every three to six months to evaluate blood pressure and check for other symptoms or side effects, such as insomnia.

When to Seek Care

Emergency medical attention is needed right away when serious side effects occur, and these include symptoms of a cardiovascular event.

Signs You Should Seek Medical Care

  • You are experiencing chest pain.
  • You have shortness of breath or difficulty breathing.
  • You feel weakness on one side of the body.
  • Your speech is slurred.

The Effectiveness of TRT

The many possible side effects of TRT should be strongly considered before you begin taking testosterone. Unfortunately, there is limited research on the long-term safety of TRT. Some studies have discovered serious risks that were linked with TRT — particularly with long-term use.  

Some significant findings from studies on TRT include the following:

  • Testosterone has been shown to increase the prostate size by 12 percent.
  • There was no link discovered between testosterone levels and prostate cancer development.
  • In a study involving 312 men with hypogonadism, testosterone replacement therapy did not worsen prostate symptom scores, nor did it negatively impact lower urinary symptoms (such as maximum urinary flow rates).
  • One study found that men taking testosterone had a 30% higher risk of death, heart attack, or stroke compared to those not taking TRT. However, many more studies have not demonstrated this cardiac risk.
  • Many experts feel that polycythemia (a condition where red blood cells are elevated) is a common side effect of TRT. Blood donation (phlebotomy) is solution for men with elevated hematocrit while taking TRT.

These research findings do need to be taken in moderation, however, due to the fact that more research needs to be done to definitively prove the long-term side effects of TRT.


There are many positive benefits of TRT that may enhance the overall quality of life for those with low testosterone levels. Before taking TRT, it’s important to examine all the pros and cons of its safe and effective use. In some instances, the benefits of TRT may outweigh the risks. Keep in mind that although TRT has been linked with BPH (prostate gland enlargement), polycythemia, and sleep apnea, the evidence is not substantial enough to fully back up many of the potential risks

Having an in-depth conversation with your healthcare provider before deciding on TRT is an important first step. 

With proper monitoring by the healthcare provider, including thorough health history, regular office visits, and frequent lab checks, TRT may be a safe and effective treatment for some people with low testosterone levels.

A Word From Verywell

Men are encouraged to seek medical advice and ask their doctors for advice on the effectiveness o testosterone replacement therapy in their particular situation.

1 Source
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  1. American Urological Society. Evaluation and Management of Testosterone Deficiency (2018).

Additional Reading