How does Testosterone Replacement Therapy (TRT) Work?

Clock 13 mins
30th Mar 2021
By: Project Alpha Team

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Testosterone is a male sex hormone that regulates sperm count and sex drive. It also affects other aspects of your health, including muscle mass, body fat, mood, red blood cell count and bone density. Normal testosterone levels range between 300 ng/dL and 1,000 ng/dL. If your blood test reveals your testosterone levels are below the norm, your healthcare provider may suggest Testosterone Replacement Therapy (TRT) – a treatment option for low testosterone.


Why does Testosterone Decrease with Age?

Testosterone is produced naturally in your body, but this process slows down as you age. In a recent study, researchers found that the average male’s testosterone production declines by about 1% to 2% every year. This is part of the natural process that begins in a man’s 30s or 40s.

Your testicles will produce less testosterone as you age. Low T levels cause your hypothalamus to produce less GnRH (Gonadotropin-releasing hormone), which in turn, will cause your pituitary gland to secrete less LH (Luteinizing Hormone). Low LH will cause low levels of testosterone production. It’s important to mention that LH binds with receptors in Leydig cells (certain cells in your testes). This leads to the release of testosterone.


Symptoms of Low Testosterone

Men naturally begin losing part of their testosterone at the age of 30 or 40. A rapid decline in T-levels may indicate a health problem referred to as low testosterone (Low T). The common symptoms of low testosterone include:

  • Low libido or sex drive
  • Erectile dysfunction
  • Low energy levels and fatigue
  • A decrease in muscle mass
  • Difficulty in concentrating
  • Facial and body hair loss
  • Irritability
  • Depression
  • Low sense of general wellbeing

Some men try to diagnose themselves with low testosterone. The challenge with self-diagnosis is that most symptoms of Low T are normal to ageing, which is why self-diagnosis is not reliable. A testosterone level test ordered by a doctor is an effective way to determine your T-levels. If the exam process reveals that you have low testosterone, your doctor will recommend a treatment option.


Testosterone Replacement Therapy (TRT)

Men who are testosterone deficient should get replacement therapy as a treatment option. According to the Institute of Medicine, approximately 4-5 million men are in this category, but only 5 percent of them are getting testosterone in the United States.

If you have been diagnosed with Low T, testosterone replacement therapy could be the answer to your sexual health woes. TRT is also known as androgen replacement therapy, and it is majorly used to treat Low T levels. Research suggests that TRT can be helpful in enhancing sexual performance, building muscle mass, and achieving higher energy levels. But how does TRT work? Are there some caveats?


Can TRT make you feel more energetic?

Suppose you have abnormally low levels of testosterone; boosting the level of this hormone with TRT can help cure some of the symptoms of low-T. One of those symptoms is low energy or fatigue. So, it is accurate to say that TRT can potentially bring your energy levels back to normal and increase your libido or sex drive. You may also notice a significant drop in body fat and an increase in muscle mass after TRT.


Forms of TRT

TRT is available in different forms, but all can help improve your T-levels. The common forms of TRT include:


TRT injections are an effective way to get bioidentical hormones. These injections work similarly to your body’s naturally produced testosterone. Injections have been studied and proved to be clinically useful, giving you control over your TRT dosage along with the chance to track how the therapy is impacting you.

Testosterone injections are administered to your muscle tissues, which means they’re instantly absorbed into your bloodstream, giving the quickest result of all forms of TRT. Additionally, TRT injections give the provider better control of the TRT dosage they are administering to you. With other forms of TRT, it is impossible to get an exact dosage. Alternatives like pellets, for instance, are generally difficult to adjust. However, with injections, the doctor can modify your dose with ease as you get an injection after every number of days. This ensures the doctor has extra control to help you regain healthy testosterone levels.

Testosterone injections are particularly effective on men with actual low T levels. After the blood test, we will be able to ascertain your testosterone levels and give the proper dosage.


Testosterone pellets or implants like Testopel are small. They are implanted under your skin to slowly release testosterone for three to six months. The advantage of implants as the hypogonadism treatment method is that you only need to go into a healthcare facility for the procedure four times a year. This is because the implants last at least three months before being entirely absorbed into your body.

Transdermal (Skin Patch) Testosterone

Transdermal or skin patch testosterone comes as a patch that you apply to your skin. It is usually applied at night, between 8:00 PM and midnight. Before using these patches, carefully read and follow the directions in the prescription label and ask the pharmacist or doctor to explain parts that you do not understand.

If you wear too many patches or longer than recommended, too much testosterone will be absorbed into the bloodstream. There is a good chance you will experience symptoms of testosterone overdose, which include shortness of breath, dizziness, chest pain, nausea, vomiting, itching, and more. Call your doctor if you experience such symptoms after using the testosterone skin patches.

Testosterone Gels

This is one of the different forms of TRT for the treatment of hypogonadism (abnormally low levels of testosterone) in men. It is administered via the skin and belongs to a category of drugs known as androgens. Some of the common testosterone gels include Testim and AndroGel, which come in packets of clear gel. The gel should be applied according to the doctor’s instructions to ensure effective absorption and avoid an overdose.

Mouth Patch Testosterone

Another form of TRT is the mouth patch. Striant is a testosterone tablet that sticks to the upper gum above the incisors. It provides sustained and controlled testosterone release through the buccal mucosa (tissues that line your mouth) as your buccal system hydrates gradually. Applying Striant twice daily, in the morning and evening, offers sustained delivery of testosterone.


Testosterone transdermal patches interact with other medications, herbs, and vitamins you may be taking. An interaction is when a drug or substance changes how another drug works. This can prevent the drug from working well or cause unanticipated side effects. To prevent drug interactions, you must consult with your doctor before you start your testosterone replacement therapy. The doctor will analyse your medications carefully and determine whether or not you can safely take replacement testosterone.

Taking testosterone with some drugs raises your risk of experiencing side effects. For example, taking testosterone alongside corticosteroids or adrenocorticotropic hormone might increase fluid build-up in your body.

Other drug interactions may necessitate dosage changes. For instance, taking testosterone could decrease your overall blood sugar level. So, if you’re taking insulin, your doctor may need to reduce your insulin dosage. Taking testosterone also changes how you are blood clots. Your doctor should monitor how dabigatran, apixaban, warfarin, or any other blood-thinning medication you’re taking is performing or changing your blood clotting.


TRT Warnings

Before you start taking testosterone, it is essential to know how this drug can impact men with the following health conditions:

Liver disease: For people with liver disease, taking testosterone could cause their bodies to retain excessive fluid. This could cause swelling or oedema.

Heart disease: People with heart disease are likely to experience water and salt retention if they take testosterone. This may lead to oedema (swelling) with or without heart failure.

Kidney disease: Men with kidney disease or a history of kidney disease in the family are likely to retain more body fluid if they take testosterone. This could cause oedema or swelling.

Breast cancer: Did you know that men also suffer from breast cancer? You shouldn’t use testosterone if you have breast cancer because this drug can make your health condition worse.

Overweight or obese: Testosterone intake can make it difficult for you to breathe well while you sleep, particularly if you are overweight. It can also cause sleep apnea.

Prostate cancer: You shouldn’t use testosterone replacement therapy if you are suffering from prostate cancer. This drug can make your health condition worse.

Diabetes: Taking testosterone decreases your blood sugar levels. That means patients who treat diabetes with insulin may need to reduce their insulin dosage.

Enlarged prostate: Testosterone may make the symptoms of enlarged prostate worse. If you must take this drug, your doctor should monitor you for worsening symptoms.

It is essential to mention that different men react differently to testosterone replacement therapy. For this reason, it is crucial to consult with your doctor before you start taking testosterone, particularly if you have the health conditions mentioned above. Depending on your health, your doctor may recommend a limited dosage of testosterone or advise you not to take it if it could affect you negatively.


Potential Benefits of TRT

Restoring testosterone level to the normal range using TRT can alleviate the symptoms of hypogonadism. Here are the benefits of TRT.

Improved Sexual Drive, Performance, and Function

The prevalence of ED (erectile dysfunction) increases with age. A recent study revealed that serum-free testosterone correlated significantly with erectile and orgasmic function domains of the IIEF (International Index of Erectile Function) questionnaire. Men with higher levels of sexual activity have higher bioavailable testosterone levels compared to men with low sexual activity and androgen deficiency. Correspondingly, low levels of bioavailable testosterone are associated with low sex drive and no sexual activity.

Men battling erectile dysfunction, low sex drive, and documented testosterone deficiency are candidates for TRT. Sufficient testosterone treatment can successfully restore venous leakage in the corpus cavernous, a frequent factor in erectile dysfunction in older men. Overviews of random controlled clinical trials revealed some benefits of TRT on sexual health-related outcomes. But a further study in this area is needed, particularly in older men who are not hypogonadal.

In addition to better sexual performance and function, TRT can improve the symptoms of lower urinary tract infections and bladder function by increasing your bladder capacity and decreasing the detrusor pressure at maximal flow in males with SLOH (Symptomatic Late-Onset Hypogonadism). It is crucial to mention that the role of testosterone supplementation in males with erectile dysfunction but not deficient in androgen needs further investigation to determine if TRT can improve erectile function.

Bone Mineral Density

Most men with osteoporosis, osteopenia, and fracture prevalence rate have low testosterone levels. The prevalence of osteoporosis in androgen-deficient men is double that of men with normal testosterone levels. A recent study revealed that bone density in males battling low testosterone levels increases with testosterone supplementation or substitution, provided the dose is sufficient. While the normal adult bone mass may not be achieved, testosterone produces this impact by increased osteoblastic activity and through aromatization to oestrogen, reducing osteoclast activity.

Healthy Heart and Proper Blood Circulation

A healthy heart pumps sufficient blood to the rest of your body, providing your organs and muscles with the oxygen necessary for an excellent performance. Testosterone facilitates the production of red blood cells in your bone marrow. This could be the reason low levels of testosterone are associated with various cardiovascular risks.

However, it is important to investigate whether TRT can help lower the risk of heart disease. An in-depth review of various studies in 2000 revealed that men with heart disease who took supplemental testosterone saw only slight improvements. Some study participants increased their walking distance by about 33%. Another review found that testosterone hormone therapy widened healthy arteries but didn’t have an impact on angina pain.

In a more recent study that involved 83000 males, researchers found that males whose T-levels normalized are 24% less likely to suffer from a heart attack. They were also 36% less likely to experience a stroke.

More Muscle and Less Body Fat

Generally, testosterone is responsible for a higher amount of body muscle mass. A lean body mass can help increase energy and control weight. For males with low T-levels, studies reveal that effective treatment can increase muscle strength and size while decreasing your body fat mass. Some men reported a significant change in lean body muscle & mass but no positive change in strength. It is likely that you will see the benefits of TRT when you combine this treatment option with exercise and strength training.

Improved Mood

Low T-levels are linked to poor quality of life. As mentioned earlier, the common symptoms of low T-levels include fatigue, irritability, and depression. However, a recent study revealed that these symptoms are common in men with hypogonadism. Males whose bodies experience a normal, gradual decrease in T-levels don’t experience depression.

The overall impact of TRT on mood varies widely. Males with hypogonadism reported better mood, overall wellbeing, reduced irritability, and fatigue. Some researchers also believe that TRT could also be a reliable anti-depressant treatment.

Better Mental Health

Sufficient testosterone levels in your body are associated with spatial abilities, better verbal memory, and effective mathematical reasoning. Medical research has revealed that men with higher ratios of overall testosterone in their bodies have a lower risk of Alzheimer’s disease. If you do not have sufficient T hormone in your body, medical researchers suggest that testosterone replacement therapy could be an effective way of getting enough levels of this hormone.

There is also sufficient evidence for a strong correlation between mental abilities like faster processing speed and higher levels of testosterone. In various studies, testosterone treatment for older males, particularly 34 years to 70 years old, showed an improvement in spatial memory.

Keep in mind that taking extremely high doses of testosterone will not make you a genius. The reality is that excessive testosterone can affect you negatively. So, it is recommended to stick two prescription doses and take the prescribed drugs according to the doctor’s instructions.


Side Effects of TRT

Medical scientists and researchers are still trying to fully understand the side effects and risks of testosterone replacement therapy. According to Harvard Health, most existing studies have limits such as using larger than usual doses of testosterone or paying small in size. As a result, there is still heated debate over the risks and benefits of testosterone supplements. For instance, it has been said to both decrease and increases the risk of some types of cancer.

An article published in the journal Therapeutic Advances in Urology in 2016 suggests that some of the conflicting opinions are a result of overzealous media coverage, particularly in the US. There are risks and side effects of testosterone replacement therapy that you should know. These include:

Infertility: Men who take supplemental testosterone without clear medical indication unknowingly set themselves up for severe medical conditions such as infertility. This is because your brain stops instructing your body to naturally produce testosterone when it senses there is enough level of this hormone in your body. Over time, this can result in testicular cell damage and visible shrinkage of testicles which inhibits sperm production.

Heart-related problems: If you carefully read the prescription labels or listen to most commercials to combat low testosterone, you will hear or realize that testosterone hormone therapy is associated with a higher risk for cardiovascular conditions such as heart attacks, strokes, and blood clots. In one study, researchers found that older men undergoing testosterone replacement therapy had a higher risk of developing plaque build-up in arteries over the course of 12 months compared to those who didn’t.

Impact on the prostate: For many years, urologists believed that TRT could cause prostate cancer. However, that link has been debunked, but medical scientists believe that this therapy can have a negative impact on the prostate gland in men who have health conditions such as benign prostatic hypertrophy. This is why it is essential for men with an enlarged prostate to receive appropriate screening before they undergo testosterone replacement therapy.

Mood-related issues: If you are looking to boost your bodybuilding efforts by turning to extremely high doses of supplemental testosterone sold in the black market, think twice. Extremely high T-levels can cause roid rage, which will make you angry. However, when dosed appropriately, testosterone supplements can offer some relief from depressive symptoms associated with low-T.

Other risks include:

  • Difficulty in breathing
  • Chest pain
  • Low sperm count
  • Swelling in the legs or hands
  • Speech difficulties
  • Lower HDL (good) cholesterol
  • Sleep apnea
  • Acne and other similar skin breakouts
  • Pulmonary embolism
  • Stroke
  • Deep vein thrombosis

It is essential to mention that TRT may have different side effects on different users. Besides, some of the health risks mentioned may be caused by other health conditions. Therefore, it is best to discuss any possible side effects with your doctor if you’re already undergoing TRT.


The Effectiveness of Testosterone Replacement Therapy

Before you undergo TRT, it is recommended to consider the side effects of this therapy, drug interactions, and other essential factors. Unfortunately, there’s limited research on the short-term and long-term impact and safety of TRT. So, it is best to consult with your doctor to determine whether or not TRT is the best treatment option for your declining testosterone levels. Here are essential facts about the effectiveness of TRT.

  • Supplemental testosterone has been shown to enhance the prostate size by 12%.
  • There is no known link (but speculation) between T-levels and the development of prostate cancer.
  • One study showed that males undergoing TRT had a higher risk of heart attack and stroke than those who didn’t undergo TRT.
  • Most experts believe that polycythaemia is a common side effect of TRT. So, phlebotomy is a reliable solution for men with high haematocrit while undergoing TRT.

Further research is necessary to understand the full spectrum of benefits of TRT and its effectiveness. The research findings discussed in this article should be taken in moderation. So, talk to your doctor before you start taking supplemental testosterone.



Testosterone replacement therapy (TRT) has long been a reliable treatment option for men with hypogonadism or health conditions associated with low testosterone hormone production. Its benefits for people without an underlying condition are not as clear, despite all the marketing hype in the hormone replacement therapy industry.

If you must undergo TRT, it is recommended to get the necessary screenings, including a blood test from your doctor, who will also help you determine the best testosterone medications. This can help you regain the recommended T-levels in your body. This medical expert can also monitor your testosterone link and not any unwanted symptoms or side effects that might occur during the treatment. Some of the immediate symptoms to watch out for include slurred speech, chest pains, trouble breathing, weakness in one side of your body, and shortness of breath.

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