How TRT Works
Testosterone therapy helps restore your testosterone levels to improve your symptoms.
In the body, testosterone binds to receptors that signal your body’s muscle and bone growth. Some of it is also converted to dihydrotestosterone (DHT) which is an androgen that’s responsible for prostate health and muscle and body hair growth. You may be surprised to learn that some testosterone also turns to estradiol – better known as the female sex hormone estrogen – which men actually need for bone density, brain health, and mood regulation (Sizar & Pico, 2026).
Who TRT Helps
Testosterone therapy helps men who have low levels of testosterone and are experiencing symptoms of low T, such as low sex drive, erectile dysfunction, and low mood. Low testosterone can also cause a decrease in muscle mass and increase in body fat that isn’t explained by another condition or unhealthy lifestyle habits.
Testosterone therapy is used to treat low testosterone caused by problems with the testicles that prevent them from making enough testosterone (primary hypogonadism) or problems with the pituitary gland or hypothalamus in the brain, which are responsible for the production and release of testosterone (secondary hypogonadism). It’s also used in men with late-onset hypogonadism, which is common in men who are overweight or obese and those with Type 2 diabetes.
While testosterone replacement therapy can be beneficial for some, it’s not safe for everyone. It’s not recommended for people with sleep apnea or a history of breast cancer (yes, men can get breast cancer, too), or those with a history of prostate cancer or signs of undiagnosed prostate cancer, such as a prostate nodule or elevated PSA levels. It’s also not recommended if you have uncontrolled heart failure or have had a heart attack or stroke in the past six months. Finally, if you’re planning to start a family, testosterone therapy can significantly lower sperm count and should be avoided (Bhasin et al., 2018).
Common Uses
The FDA only approves the use of testosterone replacement therapy for men who meet the diagnostic criteria of hypogonadism and have associated symptoms. This typically requires morning blood testosterone levels under 300 ng/dL on at least 2 occasions (Sizar & Pico, 2023).
Some medical practitioners may prescribe testosterone off-label if you’re experiencing symptoms even if your blood testosterone is above 300 ng/dL.
TRT is often used to:
Boost sex drive and improve sexual function
Increase energy levels
Improve mood
Increase muscle mass and lower body fat
Improve concentration and focus
What the Evidence Supports
Testosterone replacement therapy has been extensively researched and the benefits of it for men diagnosed with clinically low testosterone levels are well-documented.
The Testosterone Trials – a coordinated series of 7 placebo-controlled, double-blind trials involving 722 older men with low testosterone found testosterone therapy improved sexual function and bone density, and corrected anemia (Snyder et al., 2018).
More recently in 2023, a large meta-analysis of 5,600 men over 40 with testosterone levels below 12 nmol/L (which falls within the low-to-normal range) found that TRT provided clinically meaningful improvement in sexual function and quality of life (Hudson et al., 2023). This was echoed in a 2024 meta-analysis of 35 trials. Not only did it show that TRT improves sexual function and quality of life, but it does so without adversely affecting blood pressure, serum lipids, or glycemic markers.
Researchers also found no relationship between TRT and cardiovascular or cerebrovascular events (Cruickshank et al., 2024). This is in keeping with the results of the TRAVERSE trial in 2023. The landmark study, which followed 5,198 patients with established cardiovascular disease or multiple risk factors for 22 months found that TRT didn’t raise the risk of major cardiac events any more than placebo (Lincoff et al., 2023).
Later in 2025, a systematic review of 25 studies showed that TRT actually leads to an improved lipid metabolism, lower inflammation, and improved vascular performance. Not only was there no compelling evidence that TRT raises cardiovascular risk, but the improvements shown may also improve cardiovascular outcomes (Ezeamii et al., 2025).
While TRT is typically effective, it’s important to remember that outcomes of treatment depend on several factors, including foundational health.
Where the Evidence Is Limited
Many of the benefits of TRT are backed by science, but it’s important to understand that most of these have been studied in older men with a clinical diagnosis of hypogonadism. Research into the claims about the benefits for younger men without clinically low testosterone is limited and some claims are exaggerated or misleading.
For example, testosterone is often marketed to men as a quick and easy way to “get ripped” and gain muscle. While testosterone does play a role in muscle building and there’s evidence that TRT can build muscle and lower body fat, the results are specifically in older men diagnosed with hypogonadism (Rojas-Zambrano et al., 2025). Research also suggests that muscle and strength gains are dependent on the TRT dose and type, and the type of exercise you do, rather than being an easy fix.
TRT is also often marketed as a quick fix for men who feel tired, sluggish, or unmotivated. It can improve energy and focus in men with medically low testosterone, but it’s not a cure for general fatigue or lack of motivation.
Everyone is different and the benefits of TRT are dependent on treatment dose and schedule that’s personalized based on an individual’s cause of low testosterone, their overall health, age, and several other factors.
Safety and Regulation
Testosterone replacement therapy is regulated by the FDA and approved only for the treatment of symptomatic and clinically confirmed low testosterone caused by medical conditions. Compounded over-the-counter testosterone products or supplements are not regulated by the FDA and have not been studied for effectiveness or safety.
TRT is typically safe and effective but regular monitoring by a doctor is required as it can cause side effects. The most common one being erythrocytosis (also called polycythemia), which is an increase in red blood cells. This can cause your blood to thicken and increase the risk of blood clots.
TRT may also raise your risk of atrial fibrillation, which is an arrhythmia that causes an irregular and often rapid heart rate and increases the risk of stroke (Lincoff et al., 2023).
Other possible side effects of TRT include breast pain and enlargement, worsening of sleep apnea, and shrinking of the testicles, and urinary changes due to the stimulation of the prostate.
The Experience
Testosterone replacement therapy begins with a thorough evaluation by a doctor to go over your symptoms and medical history. Your doctor will want to learn about your lifestyle and other factors that may be causing your symptoms and affecting your testosterone levels, such as your exercise, diet, and sleep habits, and any stressors.
Blood tests – usually a morning blood test of your total testosterone taken on two separate days – are used to diagnose low testosterone.
Your doctor may also order other blood or imaging tests to determine the cause of your low testosterone. Other blood tests may also be ordered to make sure TRT is safe for you, such as tests to measure your red blood cells, PSA levels, and liver function.
Testosterone replacement therapy is available in a few different forms, including pills, injections, and gels, patches, pellets, and nasal spray.
After you start TRT, your doctor will want to monitor your treatment to make sure it’s working well for you and not causing any adverse effects.
TRT Should Be Combined with Lifestyle Modifications
TRT should be combined with lifestyle changes that have been proven to increase testosterone levels and improve symptoms, as well as your overall health.
Weight management is often recommended because obesity lowers testosterone because body fat converts testosterone to estrogen, leading to metabolic dysfunction. Some research suggests that losing just 10 kg if you’re overweight can increase testosterone levels by 50–100 ng/dL. And exercise can help you achieve and maintain a healthy weight, as well as raise testosterone levels further and improve symptoms of low T (Walia et al., 2025).
Nutrients also play an important role in testosterone production. Vitamin D, zinc, and magnesium supplementation has been shown to increase testosterone levels. (Liu et al., 2025).
Sleep optimization and stress reduction are other important modifications for treating low testosterone. This is because both poor sleep and stress increase cortisol, which suppresses testosterone production.
The Future of TRT
Larger and long-term clinical trials are needed to confirm the benefits of TRT, not just long-term in men with hypogonadism, but also in younger men whose levels don’t quite meet the diagnostic criteria.
In the meantime, experts are looking into testosterone therapy based on several biomarkers (not only total testosterone) and adding lifestyle modifications for a tailored approach that increases T levels and improves sexual function while also improving metabolic health.
Takeaway
Testosterone replacement therapy is a safe and effective treatment for men with low testosterone, but it should be used alongside healthy lifestyle practices, such as diet and exercise, sleep optimization, and stress reduction to improve foundational health and get the most out of treatment.
