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Testosterone, a sex hormone produced by both males and females, is often associated with libido and muscle mass. This universal hormone is also responsible for much more, like sleep, bone health and even mood regulation.
But testosterone isn't an inconsequential elixir of youth and vitality without side effects. Testosterone replacement therapy must be done under careful medical supervision, and it isn't right for everyone.
What Is Testosterone Replacement Therapy?
Testosterone replacement therapy is a medical treatment where people receive a form of external testosterone. The goal of TRT is to bring testosterone levels into a normal range and alleviate symptoms of low testosterone, like mood changes, sexual dysfunction or fatigue. TRT requires medical oversight to get the initial prescription, monitor side effects and check testosterone levels over time.
Why Does Testosterone Decrease Over Time?
Both males and females produce testosterone mostly in their reproductive system, in the testes and ovaries, respectively. Both sexes also make some testosterone in the adrenal glands, small structures above the kidneys responsible for creating certain hormones.
Over time, testosterone production gradually decreases. According to the Prostate Cancer Foundation, as many as 39% of men aged 45 to 85 have low levels of blood testosterone. In women, testosterone gradually decreases with age or may sharply decrease as a result of surgical menopause.
Dr. Vinita Tandon, an endocrinologist in Mountain View, California, and medical director at Lifeforce, a clinically integrated health optimization platform through biomarker testing, says that this is due to several factors:
- Disruptions with hormone production. Age-related changes in areas responsible for testosterone production, like the brain and reproductive organs, can contribute to declining testosterone levels. Tandon says this phenomenon is called hypothalamic-pituitary-gonadal axis dysfunction.
- Reduced Leydig cell function. “Aging can lead to reduced function of Leydig cells in the testes, which are responsible for producing testosterone. This reduced function can result in lower testosterone production,” Tandon shares.
- Lifestyle and environmental factors. Both having a sedentary lifestyle and being overweight can decrease testosterone production.
- Chronic stress. Stress causes cortisol production, which is a hormone that signals the body to slow testosterone production.
- Endocrine disruptors. Exposure to endocrine-disrupting chemicals in the environment, like pesticides and plastics, may interfere with hormone regulation, Tandon explains.
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If you have symptoms of low testosterone and you have low levels of testosterone on a blood test, your medical provider may talk to you about testosterone replacement therapy.
TRT may benefit:
- Males with primary hypogonadism. Dr. David Shusterman, a urologist and the chief physician and founder of New York Urology in Manhattan, says that one of the most common reasons a younger male needs TRT is due to primary hypogonadism. “This is a condition where the testes are unable to produce an adequate amount of testosterone.” He says this could be due to various factors, like genetics, injury, infection or medications.
- Males with secondary hypogonadism. Secondary hypogonadism is a condition where the brain is unable to properly signal to the testes to produce sufficient testosterone. The condition can be caused by inflammation, HIV/AIDs, medications or aging.
- Males with age-related testosterone decline. While declining testosterone levels are a common part of aging, some men may experience bothersome symptoms, such as low energy, reduced muscle mass and diminished libido, and may want treatment.
- Females with hypoactive sexual desire disorder. Dr. Fenwa Milhouse, a urologist and sexual health expert at her practice, Down There Urology, in Chicago, says TRT doesn’t just benefit men. “It is being used safely in women at small doses to treat low libido in peri- and post-menopausal women,” she explains.
How to Get TRT Treatment
TRT is a prescription treatment that requires evaluation by a medical provider. This includes a physical exam and assessment, lab work and a discussion of your symptoms and lifestyle.
Tandon says that your medical provider must also consider and rule out other possible causes of your symptoms, such as:
- Hypothyroidism. When the thyroid, a small gland under the neck, is underactive, some people have similar symptoms to low testosterone. Fatigue, weight gain, depression and reduced libido may mimic low testosterone symptoms, Tandon says.
- Anemia. A reduced red blood cell count results in having less oxygen-rich blood in the body. Tandon explains that this can cause fatigue, weakness and reduced stamina.
- Cortisol imbalances. Both excess and insufficient cortisol can produce symptoms that might feel similar to having low testosterone. Fatigue, muscle weakness and mood changes are among these symptoms.
Your provider will need to order blood tests if there is suspicion for any of the above conditions in order to rule them out. After evaluation, your provider may determine that testosterone is medically necessary for you. TRT requires consistent monitoring to ensure the medication is effective and that you aren’t getting too much or too little. So, your provider will determine the dose and cadence of your TRT.
Types of TRT Treatments
Along with your testosterone dosage and frequency, the route for how the testosterone is given will also impact how well the treatment works for you.
Tandon says the best route varies from person to person, depending on factors like:
- How accurately testosterone levels need to be monitored.
- Side effects for each type of administration.
- Practicality, such as how likely the patient is to self-administer testosterone compared with coming in for a clinic visit.
- Individual response to that specific route.
Testosterone may be given by:
- Gel or cream. Tandon says, “Topical testosterone that is applied once or twice daily provides the most stable levels of testosterone compared to weekly injections. However, it's more prone to user error.” This method requires a daily application.
- Intramuscular injection. Since the injection is inserted into the muscles of the thigh or hip, providers will consider how comfortable you are with needles and how likely you would be to stick to the treatment plan. Testosterone injections typically last for a few weeks.
- Pellet. A pellet is a small implant about the size of a grain of rice that is inserted under the skin in the buttock area. They release a small amount of testosterone gradually over a period of several months. It’s important to consider the healing time after pellet insertion. Tandon says she has seen delayed healing time after insertion that may prevent patients from being able to exercise for a week or two after each insertion.
- Patch. Testosterone patches are applied over the skin in a similar fashion to an adhesive bandage. They are usually applied to the back, stomach, thighs or upper arms, and the patch cannot get wet for at least three hours. The patch lasts for about seven days until it needs to be reapplied.
Is TRT Safe? Risks and Scary Side Effects
While TRT can often be safe and effective, there are some concerning and serious side effects.
Milhouse says side effects may include:
- Increased production of red blood cells, causing the potential for blood clots.
- Increased risk of sleep apnea, where breathing is interrupted during sleep.
- Testicular atrophy (shrinking testicles).
- Prostate growth, meaning regular prostate cancer monitoring is necessary.
Tandon says that some methods of TRT may be more associated with side effects like acne, balding, decline in HDL (the “good” cholesterol) or a worsened mood.
Milhouse adds, “There has been mixed data and some concern whether TRT increases the risk of cardiovascular problems like heart attacks and strokes. Fortunately, a new study published this year in the New England Journal of Medicine demonstrated that TRT does not increase the risk of cardiovascular problems.”
Some people may have low testosterone, and TRT might not be safe for them due to the concerns for side effects. Shusterman shares that he would be especially wary of patients who have a history of prostate cancer, due to the possibility of TRT stimulating existing or new cancer growth. He adds that he would also watch out for patients with severe heart, kidney or liver conditions.
“TRT can affect blood pressure, fluid balance and lipid metabolism, which could have an adverse effect on patients with (these) preexisting conditions.”
Alternatives to TRT
There are a few ways to naturally prevent the gradual decline of testosterone over time.
Shusterman recommends:
- Regular exercise, which promotes optimal circulation and hormone production.
- Maintaining a healthy weight to reduce excess fat, which can contribute to hormonal imbalances.
- Getting enough sleep to protect the body’s natural hormone production cycles.
- Reducing stress to prevent cortisol from interfering with testosterone production.
- Avoiding excessive drug and alcohol use to prevent endocrine disruption.
There are some other vitamins and supplements that claim to reduce testosterone decline, like vitamin D and zinc, but these haven’t been fully validated yet for their relationship to testosterone.
Shusterman adds, “It is important to consult with a health care professional first before making any significant changes to one's lifestyle or considering any alternative treatments for low testosterone.”
The Bottom Line
TRT is typically safe and effective under the direction of a medical provider, but there are some potentially concerning side effects, especially with prostate growth. Milhouse says that many patients do share that they experience increased libido, energy, mental alertness and increased well-being on TRT.
Shusterman adds, “The decision to administer TRT should be made on a case-by-case basis by a health care professional, taking into consideration a patient's medical history and other risk factors. Patients considering TRT treatment should consult with their health care provider to assess the potential benefits and risks of testosterone replacement therapy.”
