Is Testosterone Replacement Therapy Safe? Myths vs. Facts

Low testosterone levels can lead to significant side effects in men — such as weight gain, muscle loss, loss of libido, and much more.

Many men are turning to testosterone replacement therapy (TRT) as a solution.

TRT works, but there are some risks and potential side effects you should be aware of before you start. There are also a lot of misconceptions about what TRT can achieve — with advertisers claiming it increases energy, strength, and youthfulness.

In this article, you’ll learn everything you need to know about testosterone replacement therapy.

We cover how it works and what the benefits are, along with information on the risks and limitations of this advanced health treatment.

What is Testosterone Replacement Therapy?

Testosterone replacement therapy — TRT — is a prescription preparation of testosterone. It’s used to restore normal levels of the hormone in men suffering from testosterone deficiencies.

Marketers are claiming T injections or T supplements can increase energy, libido, strength, and youthfulness. While some of these benefits exist, TRT isn’t the miracle cure many expect.

Medically speaking, TRT is used for treating male hypogonadism — which refers to clinically deficient testosterone concentrations. The diagnosis of this condition is made through a blood test. Anybody with total testosterone levels below 10 nmol/L (300 ng/dL) is considered deficient and could be diagnosed with hypogonadism.

Most doctors won’t prescribe TRT without first identifying the cause of the condition and attempting to fix the underlying issue through other means first. The benefits of TRT are controversial at best and bring a high risk of side effects — some of which can be severe. Heart disease, stroke, and prostate cancer are all much more prevalent in men taking TRT compared to baseline.

How Does Testosterone Replacement Therapy Work?

There are a few different compounds used in testosterone replacement therapy. Synthetic androgens (male hormones) can be integrated into capsules, topical gels, or injected to boost overall testosterone or androgen levels.

Compounds that are similar to testosterone, but consist of a different chemical altogether are called anabolic steroids or anabolic-androgenic steroids (AAS).

These compounds work by binding to the same receptors testosterone normally binds to. Depending on the androgen used, the strength of the effects can vary a lot. Some compounds, such as dimethyltrienolone (no longer used) are exceptionally strong and therefore bring an increased risk of side effects. Only a few milligrams are needed for powerful testosterone receptor activation.

Other compounds, such as nandrolone are much milder and tend to have fewer side effects.

There are multiple ways of using testosterone replacement:

1. Anabolic Steroids: Injections

Intramuscular injections (injections in the thigh or butt muscles) are the most common form of TRT used today. A single dose of testosterone delivered by injection can last several days or weeks, depending on the molecule used.

The most common TRT injection prescribed in the US is depo-testosterone [2]. This form of testosterone is made by Pfizer and has been on the market since 1979. Despite how common this form of testosterone is and how much data we have available on its effectiveness, the results remain inconclusive.

The second most common injectable testosterone option is Delatestryl, which contains testosterone enanthate. This medication is made by Endo Pharmaceuticals. It also has a long duration of effects and only requires dosing every 2 weeks.

The advantages of injectable testosterone come from the fast onset of effects (instant) and long duration of effects (several days or weeks).

The disadvantage is that testosterone injections result in fluctuations in hormone levels throughout the month. Testosterone levels increase dramatically after the injection and decrease gradually over the following days or weeks leading up to the next dose.

Examples of injectable testosterone and anabolic steroids & their dose:

Delatestryl (Testosterone Enanthate) — 50 – 400 mg (twice/month)
Depo-Testosterone (Testosterone cypionate) — 100 – 200 mg (twice/month)
Drostanolone propionate — 100 mg 3 times per week (injection)
Methenolone enanthate — 25 – 100 mg/week (injection)
Nandrolone decanoate — 12.5 – 200 mg/week (injection)
Nandrolone phenylpropionate — 6 – 200 mg/week (injection)
Stanozolol — 50 mg (every two weeks)
Testosterone — 25 – 100 mg/day (three times weekly)
Testosterone propionate — 25 – 50 mg (3 times/week)
Testosterone undecanoate — 750 – 1000 mg (every 10 weeks)
Trenbolone HBC — 75 mg (every 10 days)

2. Anabolic Steroids: Patches or Gels

Patches or gels are another common form of TRT. The advantage of this method is that it provides a sustained dose of testosterone throughout the day — rather than the weekly fluctuations brought on from injectable testosterone or anabolic steroids. This form of TRT also brings a much lower risk of side effects compared to injection or oral forms.

The downside to patches or gels includes the cost (up to 10 times more expensive than injections), and the frequency of application (some need to be applied 2 or 3 times per day).

The most popular topical medication used is Natesto — manufactured by AYTO Bioscience.

Examples of topical testosterone gels or patches and the dose:

Androderm — one patch per day
AndroGel — one pack per day
Testim — on pack per day
Natesto — applied once per day

3. Anabolic Steroids: Oral Tablets

Oral tablets aren’t that common these days as a source of testosterone-replacement therapy. They tend to have a poor bioavailability and bring a higher risk of side effects.

This form of androgen replacement therapy is still used in some parts of the world and is common on the anabolic steroid black market.

The exception to this is Striant — which is a buccal tablet made by Endo Pharmaceuticals. It consists of a small tablet applied on the gums in the top row of teeth. The testosterone in this tablet is slowly absorbed throughout the day to provide sustained doses of testosterone.

Examples of oral anabolic steroids and the dose:

Danazol — 100 – 800 mg/day (oral)
Ethylestrenol — 2 – 8 mg/day (oral)
Dluoxymesterone — 2 – 8 mg/day (oral)
Mesterolone — 25 – 150 mg/day (oral)
Metandienone — 2.5 – 15 mg/day (oral)
Methenolone acetate — 10 – 150 mg/day (oral)
Methyltestosterone — 1.5 – 200 mg/day (oral)
Nandrolone phenylpropionate — 20 – 30 mg/day (oral)
Norethandrolone — 20 – 30 mg/day
Oxymetholone — 50 – 150 mg/day
Stanozolol — 2 – 6 mg/day
Striant (buccal tablet) — two per day
Testosterone — 400–800 mg/day
Testosterone undecanoate — 80 – 240 mg/day

Risks & Side Effects of Testosterone Replacement Therapy

There are a lot of risks that come along with testosterone-replacement therapy. Before you decide to try TRT, it’s important for you to weigh the risk-to-benefit ratio for your condition.

In many cases, your doctor will prescribe other treatments first and reserve TRT only as a last resort.

The immediate side effects are usually mild, involving digestive discomfort and acne formation. However, TRT is a long-term treatment — often spanning several years or for the remainder of a man’s life. The most dangerous side effects of the treatment develop several months or years after the treatment begins.

Long-term, TRT can increase a man’s chances of developing prostate or breast cancer, stroke or heart disease, and worsen symptoms of benign prostatic hyperplasia, sleep apnea, and lower sperm cell production [4].

Short-Term Side Effects of TRT

Acne formation
Digestive discomfort
Sleep apnea

Long-Term Side-Effects of TRT

Benign prostatic hyperplasia
Congestive heart failure
Increased risk of blood clots & stroke
Increased risk of prostate cancer
Reduced sperm production & testicle shrinkage

How Much Does Testosterone Replacement Therapy Cost?

TRT is a long-term treatment plan — most men take this therapy for the rest of their lives. So the best way to compare the cost of different treatments is to look at the average cost per month. This allows us to compare the cost for different forms of treatment that require separate dosing intervals.

Overall, injection is the most cost-effective way of taking testosterone. This form costs roughly 10% of the cost for watches or gels.

However, there are exceptions.

The monthly cost of testosterone replacement therapy can vary depending on the required dose and method of administration. It also depends on what part of the world you live in (the cost of medications varies by state as well as by country).

A review published in 2016 did an excellent job of summarizing the prevalence of different forms of testosterone replacement therapy, along with the average monthly costs for each medication [3].

Here’s a general cost breakdown for the most common testosterone replacement medications used today. The prices listed are averages — the actual cost may vary slightly.

Delatestryl Injections (100 mg/mL in 5 mL Vial) — $23.46/month
Depo-Testosterone Injections (100 mg/mL in 10 mL Vial) — $22.70/month
Depo-Testosterone Injections (200 mg/mL in 1 mL Vial) — $98.07/month
Natesto Gel (11 mg) — $699.21/month
Striant Buccal Tablets (30 mg) — $724.77/month
Androderm Patches (4 mg) — $195.03/month
AndroGel (1%) — $309.24
Axiron (2%) — $630.78
Fortesta (2%) — $281.80
Vogelxo (1%) — $283.69

How Long Will it Take for TRT to Work?

The physiological effects of TRT start to work right away, and some men see improvements in symptoms in a matter of days. Others only start to see improvement after several months of consistent use.

It’s hard to determine when or if TRT will work for each person, regardless of what’s causing the deficiency.

What is Testosterone? What Is It Used For?

Testosterone is the primary male hormone — responsible for regulating the male reproductive system, muscle growth, immune function, and much more.

Uses of testosterone in the body include:

Increases bone density
Regulates fat distribution
Regulates immune activity
Increases muscle mass & strength
Promotes the growth of facial & body hair
Regulates sex drive and arousal
Supports sperm production

Testosterone Deficiencies: Signs, Symptoms, & Causes

Testosterone deficiency is diagnosed when total levels are below 10 nmol/dL — however, this is a poor indicator of the holistic state of testosterone in the male body.

There are three ways to measure testosterone in men:

Total testosterone — the concentration of all testosterone in the bloodstream
Bioavailable testosterone — the total amount of testosterone minus the testosterone bound to SHBG (rendered inactive)
Free testosterone — the concentration of unbound testosterone (active testosterone)

The best marker for testosterone health in men is bioavailable or free testosterone because this measures the amount of usable testosterone in the body. It’s possible for a man to test within the healthy range in terms of total testosterone — while most of this testosterone is bound to SHBG and rendered inactive.

Healthy levels of free testosterone by age:

Age 20–30 — 5.4 – 21.2 ng/dL
Age 30–40 — 4.6 – 19.0 ng/dL
Age 40–50 — 4.3 – 17.1 ng/dL
Age 50–60 — 3.9 – 15.6 ng/dL
Age 60–70 — 3.5 – 13.9 ng/dL
Age 70–80 — 3.1 – 12.2 ng/dL
Age 80–90 — 2.7 – 10.5 ng/dL
Age 90–100 — 2.29 – 8.76 ng/dL

Signs & Symptoms of Low Testosterone

The signs and symptoms of low testosterone levels are subtle at first — the condition often goes undiagnosed for several years before more severe symptoms start to emerge.

The only way to confirm a testosterone deficiency is through a blood test.

Common signs & symptoms of low testosterone in men include:

Low libido
Low sperm count
Emotional changes
Increased body weight
Reduced muscle bulk
Enlarged or swollen breasts
Hair loss (head and body)
Lower energy levels
Poor focus & concentration

Testosterone Levels Decline With Age

It’s completely normal for testosterone levels to diminish with age.

Testosterone levels reach their peak around age 19 and remain high throughout the 20s and early 30s.

Around the 30s or 40s, testosterone levels will start to decline at a rate of about 1% each year.

By the time a man is 60 years old, his testosterone levels could be half the levels he had when he was 20.

At the same time, testosterone levels are decreasing; another problem is stirring.

A hormone, called SHBG (sex hormone-binding globulin) starts to increase at a rate of about 1.2% each year starting around age 60. This hormone binds to free testosterone in the blood and renders it inert — speeding up the loss of bioavailable testosterone even faster.

Bioavailable testosterone refers to the testosterone that has an effect on the body. It eliminates the testosterone bound to SHBG because this form doesn’t have any effect on the body.

By 75, roughly 25% of men meet the criteria for testosterone deficiency.

Other Causes of Low Testosterone Levels

The most common cause of low T levels is old-age, but there are other causes that can appear at any point in life.

A few potential causes for low testosterone levels include:

Autoimmune conditions
Genetic disorders
Radiation therapy
Undescended testicles
Infection of damage to the testicles
Surgery to the testicles

When To Turn to Testosterone Replacement Therapy

Testosterone replacement therapy is rarely used for men experiencing a natural loss of testosterone that comes along with age. Studies have shown mixed results from this treatment in older men [1]. The increased level of risk involved with TRT, especially in older men, outweighs the benefits in most cases. Especially when other forms of therapy, such as resistance training, have shown even greater improvements without the risk.

If testosterone levels are low, doctors will instead screen the patient for potential underlying causes instead. If an underlying disease is causing low testosterone, this should be managed before turning to TRT as a solution.

Think about it like this. Imagine you’re trying to fill a bathtub with water. The water is flowing from the tap, but it’s draining just as fast as you fill it up because the drain was left open. You could increase the water flow so it overtakes the amount lost through the drain, or you could close the drain and allow the normal flow of water to fill the tub.

This metaphor works for TRT too.

When testosterone levels are low because of an underlying disease, you’re essentially just turning up the flow of testosterone to try and overcompensate for the loss. The better solution (in most cases) is to find the drain (underlying cause) and close it up.

Testosterone replacement therapy should be turned to as a last resort after other solutions have been attempted first.

Other Techniques to Boost Testosterone Levels

There are a lot of things men can try to help boost testosterone levels naturally before turning to TRT.

Recent studies have shown that daily resistance training offers comparable improvements in testosterone levels as prescription TRT [5,6].

Other studies have shown supplements such as zinc [7], D-aspartic acid [8], and pine pollen [9] offer notable improvements in total testosterone levels as well.

Here are some of the natural methods men are using to boost testosterone levels:

Maintain a healthy weight — obesity is directly correlated with low testosterone levels in men.
Prioritize sleep — studies have shown that just one week of sleep deprivation lead to 10–15% lower testosterone levels compared to baseline [10].
Exercise regularly — consistent resistance training is considered one of the most reliable methods of increasing testosterone levels naturally.
Vitamin D supplementation — studies have linked low vitamin D levels in the winter to reduced testosterone levels [11].
Supplemental zinc — zinc is required for the body to produce a variety of hormones, including testosterone.
D-aspartic acid — this supplement has been shown to increase production of follicle-stimulating hormone (FSH), which is tasked with regulating the release of testosterone [12].
Pine pollen supplementation — pine pollen provides over a dozen nutritional components the body requires to produce testosterone and other androgens.

Key Takeaways: What is TRT & When Should it be Used?

Testosterone replacement therapy (TRT) is a prescription treatment option for men suffering from hypogonadism or testosterone deficiency. It involves taking a tablet, oral gel, topical patch, or injection of a synthetic form of testosterone for several months or years at a time. Many men who start taking TRT will be using it for the rest of their lives.

There are a lot of risks to using TRT, so it’s important for men to know the potential dangers and weigh the risk to potential benefits.

Most doctors won’t start with a prescription for TRT. Instead, other methods are tried first to see if testosterone levels can be improved through other means first.

If all else fails, TRT remains a viable option for boosting testosterone in clinically deficient patients.

TRT is not recommended for people looking to use it to boost energy, increase strength or muscle tone, or improve physical performance.

Sources Used in This Article

Borst, S. E., & Mulligan, T. (2007). Testosterone replacement therapy for older men. Clinical interventions in aging, 2(4), 561.
Snyder, P. J. (2012). Testosterone treatment of male hypogonadism. UpToDate, Matsumoto, AM (Ed), UpToDate, Waltham, MA.
Luthy, K. E., Williams, C., Freeborn, D. S., & Cook, A. (2017). Comparison of testosterone replacement therapy medications in the treatment of hypogonadism. The Journal for Nurse Practitioners, 13(4), 241-249.
Osterberg, E. C., Bernie, A. M., & Ramasamy, R. (2014). Risks of testosterone replacement therapy in men. Indian journal of urology: IJU: journal of the Urological Society of India, 30(1), 2.
Lambert, C. P., Sullivan, D. H., Freeling, S. A., Lindquist, D. M., & Evans, W. J. (2002). Effects of testosterone replacement and/or resistance exercise on the composition of megestrol acetate stimulated weight gain in elderly men: a randomized controlled trial. The Journal of Clinical Endocrinology & Metabolism, 87(5), 2100-2106.
Kraemer, R. R., Kilgore, J. L., Kraemer, G. R., & Castracane, V. D. (1992). Growth hormone, IGF-I, and testosterone responses to resistive exercise. Medicine and Science in Sports and Exercise, 24(12), 1346-1352.
Netter, A., Nahoul, K., & Hartoma, R. (1981). Effect of zinc administration on plasma testosterone, dihydrotestosterone, and sperm count. Archives of andrology, 7(1), 69-73.
D’Aniello, A., Di Cosmo, A., Di Cristo, C., Annunziato, L., Petrucelli, L., & Fisher, G. (1996). Involvement of D-aspartic acid in the synthesis of testosterone in rat testes. Life sciences, 59(2), 97-104.
Adenigba, I., Tumbokon, B. L. M., & Serrano, A. J. (2017). Androgenic and Anabolic effects of Pinus tabulaeformis Carr. Pollen in Clarias gariepinus.
Leproult, R., & Van Cauter, E. (2011). Effect of 1 week of sleep restriction on testosterone levels in young healthy men. Jama, 305(21), 2173-2174.
Wehr, E., Pilz, S., Boehm, B. O., März, W., & Obermayer‐Pietsch, B. (2010). Association of vitamin D status with serum androgen levels in men. Clinical endocrinology, 73(2), 243-248.
Topo, E., Soricelli, A., D’Aniello, A., Ronsini, S., & D’Aniello, G. (2009). The role and molecular mechanism of D-aspartic acid in the release and synthesis of LH and testosterone in humans and rats. Reproductive Biology and Endocrinology, 7(1), 120.