Testosterone plays a vital role in the human body. Its effects increase muscle and bone strength and density, induce hematopoiesis, and drive libido and sexual function. Testicular production of testosterone typically declines with age, which can result in its beneficial effects being diminished. Testosterone replacement therapy (TRT) has been used as a treatment method to address low levels of testosterone in men, but what are the benefits and peculiarities?

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 is 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).

Treatment

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.

Injections

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

Subcutaneous

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 an inconvenience and a small risk of infection.

Oral

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.

Nasal

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 testosterone 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.

Symptoms

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.

The 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.

Contraindications

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.

What is Testosterone Replacement Therapy?

Testosterone replacement therapy (TRT) is approved by the United States Food and Drug Administration as a treatment method for men who lack or have low levels of testosterone alongside an associated medical condition. Late-onset hypogonadism (LOH) is one such condition that necessitates the use of TRT and due to an increasingly aged population, has increased in prevalence in recent years.

Late-onset hypogonadism is classified as a clinical and biochemical syndrome whereby there is a decrease in serum testosterone produced by the testes. Men with LOH can experience a range of symptoms including an increase in body fat, depressive or low mood, a decrease in libido, a reduction in muscle mass and strength, and a decrease in bone density which can lead to the onset of osteoporosis.

The administration of TRT is used to restore serum testosterone levels to an appropriate physiological range for the patient’s age, and to improve symptoms in hypogonadal men. TRT is currently classified by route of administration which includes intramuscular, transdermal, nasal, buccal, and subdermal. Like all prescription medications, TRT is considered to have a range of beneficial effects alongside adverse effects which should be communicated to patients seeking to undergo treatment.

What are the Benefits of TRT?

Research has highlighted a range of health benefits that can develop by increasing levels of testosterone through TRT.

Cardiac Health

Research has found a link between the onset of cardiovascular disease and testosterone levels. A longitudinal study following 3,518 men over 17 years, found that men with low levels of testosterone were twice as likely to die due to cardiovascular disease than those with normal or expected levels of serum testosterone.

Subsequent research has found that even in middle-aged patients, having higher levels of testosterone was linked to good cardiovascular health profiles; higher levels of high-density lipoprotein cholesterol, and low levels of insulin, systolic blood pressure, and triglycerides.

Based on this body of literature, it could be suggested that men with low testosterone levels may be more at risk of developing cardiovascular problems, and as a result, may improve their cardiac health by undergoing TRT.

Increase in Muscle Mass

One of the well-researched adverse effects of low serum testosterone is a decrease in muscle mass and strength, which can negatively affect mobility. Research investigating the impact of TRT in a group of hypogonadal men found that TRT administration was able to reverse some of the aforementioned effects to some extent.

An increase in lipid oxidation and muscle mass was observed and resulted in an improvement in overall lean body mass. Many patients reported that these effects boosted their quality of life, especially those that had limited mobility.

Increase in Mood

The relationship between mood disorders such as depression and low levels of testosterone has been found to be significant in older men. One study found that up to two-thirds of men with treatment-resistant depressive symptoms also had low testosterone. Furthermore, an analysis of depressive symptom scores in men from the general population found that those with testosterone deficiency reported higher symptom scores, especially with regard to anxiety.

The use of TRT could, therefore, be beneficial in reducing the prevalence or severity of mood disorders such as depression which may have gone on to develop in men with low testosterone without TRT as an intervention.

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