The 2026 Levels Guide to testosterone replacement therapy
As TRT presciptions and influencer chatter skyrocket, research shows its potential, particularly for aging males. But TRT isn’t entirely risk-free. Here's everything you need to know about testosterone replacement therapy.
Testosterone replacement therapy (TRT), which helps improve symptoms of low testosterone, seems to be all the rage. Estimates based on IQVIA data indicate that testosterone prescriptions in the U.S. climbed from approximately 7.3 million in 2019 to over 11 million by 2024.
It's understandable, since all men lose testosterone as they age, and for some, the symptoms can be less than thrilling: fatigue, increased body fat, decreased muscle mass, erectile dysfunction, and more. The condition can also make it harder to stay active and raise the risk of health problems such as heart disease and osteoporosis.
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TRT can help some men who face symptoms of low testosterone. But as with any medical treatment, it's best to get the facts first.
We'll cover how TRT can affect overall health, who might benefit from it, and how to get started if you think it could help you.
Understanding testosterone and metabolic health
Testosterone is involved in several metabolic health processes, including energy production, body composition, insulin sensitivity, and bone density.
It's not fully clear how testosterone acts on metabolism. It may control the expression of proteins involved in regulating glycolysis (which converts glucose into energy), glycogen synthesis (which stores glucose for energy use), and lipid (fat) and cholesterol processing.
Testosterone helps boost muscle mass by stimulating protein synthesis (the process of repairing and growing muscles after exercise) and inhibiting muscle protein breakdown. It may also reduce fat by increasing the number of beta-adrenergic receptors, which, in turn, promote lipolysis (the breakdown of fats for energy use).
Testosterone may increase insulin sensitivity through its effects on fat and muscle mass and its activation of insulin cells, which may increase glucose uptake in muscle and fat tissue.
Lastly, testosterone increases bone density by stimulating the production of cells that form new bones and heal existing ones (osteoblasts) and limiting the activity of cells that break down bone tissue (osteoclasts).
Testosterone's decline and its impact on health
Testosterone naturally declines with age in men. Levels start to drop in a guy's mid-30s and continue to decrease at an average rate of 1.6 percent per year (though this rate can vary significantly from person to person).
Given testosterone's key role in so many aspects of metabolic functioning, it's no surprise that low levels (generally considered below 300 ng/dL) can cause several problems, such as low energy, decreased bone density, more body fat, higher triglycerides and low-density lipoprotein (LDL) cholesterol, and lower insulin sensitivity.
Some research also suggests a link between testosterone deficiency and obesity, metabolic syndrome, and Type 2 diabetes. Low testosterone may increase visceral fat, which can lead to insulin resistance. Up to 40 percent of men with Type 2 diabetes have testosterone deficiency.
What is TRT?
Testosterone replacement therapy (TRT) is a treatment option for many men dealing with testosterone deficiency due to hypogonadism, the catchall term for your body not producing enough testosterone. This condition can result from damage or malfunction in the testicles, pituitary gland, or hypothalamus.
Signs of hypogonadism include:
- Lower sex drive
- Erectile dysfunction
- Fatigue
- Depression
- Decrease in hair growth
- Decreased muscle mass
- Less bone mass
- Difficulty concentrating
- Hot flashes
These symptoms can mimic the effects of other conditions or medications (such as hypothyroidism), so it's essential to consult with a doctor to understand their cause.
How is TRT used?
Before prescribing TRT, your healthcare provider needs to confirm your testosterone levels with a blood test. They may also order additional blood tests (such as thyroid-stimulating hormone, prolactin, and hematocrit) to help determine the cause of hypogonadism, rule out other conditions, and assess for potential complications from TRT.
TRT entails taking manufactured testosterone to help bring T levels up. It doesn't cure low T or address any root causes.
TRT comes in many different forms, including:
- Topical (skin gel and patch)
- Oral (capsule, pill, and buccal tablets)
- Nasal gel
- Pellets (implanted under the skin every three to six months)
- Injection (intramuscular or subcutaneous)
For most people, selecting a form of TRT primarily depends on personal preference and cost.
- Injections are typically more cost-effective than the other options and more likely to be covered by insurance. However, they require the use of needles and can cause pain at the injection site.
- Gels avoid the use of needles but are more expensive than injectables and can be accidentally transferred through the skin to women and young children.
- Pellets are longer-acting than other forms. But they tend to be more expensive than injections or gels and can also cause pain at the injection site.
- Pills avoid some of the risks of injections, gels, and pellets, but are also costly.
After you start TRT, your provider will monitor your testosterone levels every three to six months during the first year, and then annually if your levels improve and remain stable. If you don't see any benefit after three to six months, your symptoms may not be due to low testosterone, and you may need to stop taking it.
Understand that TRT is often a lifelong commitment. If you stop using it, your testosterone levels will drop again because your body will need to regain the ability to produce its own testosterone (more on this below).
Who shouldn't use TRT?
TRT is only FDA-approved for men whose testosterone levels have declined due to a medical condition (not due to aging).
TRT is generally not recommended in men with untreated severe obstructive sleep apnea, uncontrolled heart failure, recent myocardial infarction or stroke (within the past 6 months), active prostate or breast cancer, or markedly elevated hematocrit.
That said, some healthcare providers will prescribe TRT to men who have low testosterone and are exhibiting symptoms---even if they don't have a medical condition that's causing low testosterone.
"If you look at the two major medical societies that put out the literature, it's the Endocrine Society and the American Urological Association (AUA)," says Jesse Mills, health science clinical professor and director of the Men's Clinic at UCLA. "Their guidelines say to consider testosterone replacement for a man who has symptoms of low testosterone and a total testosterone of less than 300 ng/dL [regardless of whether he has a medical condition]."
Mills adds that this position differs from FDA guidelines, which don't support treating low testosterone due to aging alone.
Still, before prescribing TRT, your provider may recommend trying to boost testosterone naturally by some or all of the following evidence-based lifestyle changes to see if they help:
- Losing weight
- Doing aerobic exercises (especially at high intensity)
- Lifting weights
- Getting enough sleep
- Eating a Mediterranean diet
How will taking TRT affect metabolic health?
TRT can offer several metabolic health benefits, including gains in muscle mass, stronger bones, and better insulin sensitivity. However, it's not risk-free, and more research is needed to clarify some of the findings.
Body composition and muscle mass effects
Numerous studies have found that TRT may significantly increase lean body mass---by 5.7 percent, according to one meta-analysis of 31 randomized controlled trials looking at injectable TRT. It may also substantially reduce fat mass in men over 40, likely because the therapy promotes protein synthesis and lipolysis. In one study, hypogonadal men lost 10.5 percent of their initial body weight after five years of TRT. Combining TRT with resistance training may lead to even greater muscle gains.
These effects on lean muscle mass may explain why some studies have shown TRT-related improvements in hand and leg strength in the same age group, while other studies have found increases in chest strength and stair-climbing power. But the findings aren't uniform, and more research is needed to establish definitive results.
In addition, in one study, TRT increased bone mineral density (the amount of calcium and other minerals in bone) by 7.5 percent in the lumbar spine and 5 percent in the femur. In another study, it increased the mean estimated spine bone strength by 10.8 percent in men 65 and older. TRT stimulates osteoblasts and inhibits osteoclasts, thereby improving bone health.
In some cases, TRT can cause male breast growth, a.k.a. gynecomastia. This happens because your body converts some testosterone into estrogen, so when you increase T levels, estrogen levels can rise as well. However, this effect is often manageable through lowering the dosage of testosterone, switching to a different formulation, or taking medications such as aromatase inhibitors, which block the enzyme that converts testosterone to estrogen.
Effects on insulin sensitivity and diabetes
TRT shows great promise for improving not only the symptoms of low testosterone in men with Type 2 diabetes, but also aspects of diabetes itself, such as blood sugar levels.
A review of 18 studies concluded that TRT improves insulin sensitivity in hypogonadal men with Type 2 diabetes and metabolic syndrome, as evidenced by lower HOMA-IR (homeostatic model assessment of insulin resistance) scores. The men ranged in age from their mid-40s to mid-60s. Similarly, it improved fasting glucose and fasting insulin in this population.
TRT may increase insulin sensitivity by reducing obesity and enhancing insulin receptor responsiveness, thereby improving glucose uptake.
Across studies, TRT was associated with modest reductions in HbA1c; in one review, mean values in treated groups declined from roughly 7.2% to 6.6%. TRT's effects on insulin sensitivity and fat reduction are believed to play a role.
Finally, when combined with diabetes medication, TRT may help achieve diabetes remission. In one study of 356 men (who averaged 61 years of age), one-third of those receiving TRT achieved remission after about 9 years of treatment, and 84% of men taking TRT reached their target A1C level. No one in the control group achieved a remission of their diabetes or reduced their HbA1C levels.
Effects on cholesterol and heart health
TRT may positively affect cholesterol, though the findings aren't conclusive. It's unclear how TRT interacts with cholesterol, but it may be related to its effects on fat reduction, insulin sensitivity, and cholesterol removal from white blood cells.
Several studies and meta-analyses have shown that TRT can lower triglycerides in hypogonadal older men, particularly those with Type 2 diabetes. One study found a sustained reduction in triglycerides in this group over five years. Individual studies and meta-analyses have also shown slight to significant decreases in LDL and total cholesterol in older men taking TRT, particularly when they have taken it for at least 1 year.
The effects on high-density lipoprotein (HDL) are mixed. One study found increases in HDL in 261 hypogonadal middle-aged and older men over five years of use, and another study echoed these findings in 255 men between 33 and 69 who received testosterone for up to five years. But a review of four studies involving 181 hypogonadal men, aged roughly 30 to 60, found no significant increase in HDL. However, these studies had small sample sizes and were shorter in duration.
Cardiovascular and blood health
Large trials suggest that TRT does not increase the risk of major adverse cardiovascular events when appropriately prescribed and monitored. However, it has not been shown to improve cardiovascular outcomes and may increase the risk of certain adverse events.
One of TRT's key effects in older hypogonadal men is to increase iron availability, in turn promoting red blood cell production. This can boost hematocrit (the percentage of red blood cells) and hemoglobin (a protein in red blood cells that carries oxygen throughout the body). These effects may correct age-related anemia. By also increasing blood flow and oxygen use in muscles, TRT may modestly improve aerobic capacity (the amount of oxygen the body can use during sustained physical activity), allowing you to work out longer and with less fatigue.
However, more red blood cells can also thicken blood, potentially increasing the risk of clots and slightly boosting blood pressure. The TRAVERSE study (which evaluated TRT's cardiovascular safety in 5,246 men aged 45 to 80) found that men receiving daily transdermal testosterone gel experienced a slight average increase in systolic blood pressure of 0.3 mmHg compared to the placebo group after six months. As a result, the FDA mandated that labeling changes, including this risk, be added to testosterone products in February 2025. Still, some smaller studies have found that TRT lowers blood pressure, including one study published in the World Journal of Men's Health in 2024 that followed 737 men for eight years.
In addition, TRT was once thought to increase the risk of cardiovascular events, such as heart attack and stroke. But the research is inconclusive. The TRAVERSE study found that the risk wasn't significantly higher among men receiving TRT than among men not using TRT.
"The TRAVERSE trial is basically saying there does not appear to be a signal that testosterone replacement increases anybody's risk of coronary disease, or any kind of myocardial event or cerebrovascular event," Mills says. The trial did find higher rates of atrial fibrillation and pulmonary embolism among men receiving testosterone, underscoring the importance of individualized risk assessment.
Other risks
Beyond the side effects mentioned above, TRT has other potential risks.
"The biggest risk to a man with testosterone replacement therapy is that it is a fantastic form of birth control," Mills says. It can shrink the testicles and reduce sperm count, causing infertility within a few months (though the timeframe can vary).
TRT will also cause your testicles to stop producing testosterone. The administration of testosterone from the treatment signals to the brain that it is already receiving testosterone, so it suppresses the body's systems responsible for producing it. If you stop taking TRT, your body will take anywhere from a few months to a few years to begin naturally producing testosterone again. Recovery is more difficult the older you are and the longer you use TRT.
And while TRT doesn't appear to raise the risk of prostate cancer, it can increase the level of prostate-specific antigen (an indicator of prostate conditions such as benign prostatic hyperplasia and cancer). So men taking TRT need to have their PSA level monitored during treatment.
How do I get started with TRT?
Low testosterone can be a significant concern for men as they age. The symptoms can hamper physical performance and create serious health complications. TRT can improve many of the symptoms of low testosterone, and healthcare providers are increasingly recognizing its potential to enhance the quality of life for men struggling with this issue.
If you think you could benefit from TRT, talk to your doctor. You'll need a blood test to get a diagnosis, and your provider will want to learn more about your symptoms. But coming to your appointment with a balanced understanding of how TRT works will enable you to have a more productive conversation as you explore potential treatment.
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