How Does Testosterone Replacement Therapy Work—And Is It Right For You?

Widely known for its far-reaching impacts on health and well-being—including muscle mass and libido—declining testosterone levels are a big concern for many men. An estimated 20 percent of adolescent and young adult men in the U.S. are testosterone deficient. That number grows to 40 percent among men between 45 and 50. The good news: There’s plenty you can do to help levels bounce back, from adjusting your exercise routine to making dietary changes to supplementing with certain herbs. There’s also a medical solution for waning testosterone levels that’s gaining mainstream appeal: testosterone replacement therapy (TRT). 

While TRT is becoming more and more common, few men understand what testosterone replacement therapy is, exactly. We tapped a team of hormone specialists for all of the details so that you can make a truly informed decision about whether TRT might be a good move for you.

• ABOUT OUR EXPERTS: Lisa Golding-Granado, M.D., is a board-certified internal medicine specialist who focuses on hormone health and the medical director of Serotonin Centers of Colts Neck, New Jersey. Andrew Y. Sun M.D., is a board-certified urologist and the chief medical advisor for Marius Pharmaceuticals, a health organization helping individuals achieve healthy testosterone levels. 

The Role Of Testosterone

Testosterone is best known for helping men develop the aesthetic attributes associated with traditional masculinity, such as facial hair, body hair, an Adam’s apple, widened jaw, and thickened brow, according to Lisa Golding-Granado, M.D., a board-certified internal medicine specialist who focuses on hormone health and medical director of Serotonin Centers of Colts Neck, New Jersey. That’s why it’s colloquially referred to as the male sex hormone. 

This androgenic hormone, however, does far more than affect how men look; it also has a widespread influence on overall health and well-being. “Testosterone plays a crucial role in muscle growth and maintenance, bone mass, red blood cell creation, sperm production, and fertility,” Golding-Granado says. It also boosts overall energy levels, plays a role in sex drive, supports healthy inflammation levels, and may positively impact mood and cognitive function, she adds.

Read More: 7 Signs You Should Have Your Testosterone Levels Tested

When a man’s testosterone levels become suboptimal—which is anything outside of 300 to 1,100 ng/dL of testosterone in their blood—he may experience a range of non-desirable symptoms, such as depression, anxiety, reduced muscle mass, increased belly fat, fatigue, sleep disruption, erectile dysfunction, and mood changes, according to Golding-Granado. Additionally, “men with low testosterone levels may be at an increased risk of developing medical conditions such as obesity, type 2 diabetes, heart disease, and osteoporosis,” says board-certified urologist Andrew Y. Sun M.D., chief medical advisor for Marius Pharmaceuticals, a health organization helping individuals achieve healthy testosterone levels. 

Why and When Testosterone Levels Drop

The most common cause of low testosterone is something you have no control over: aging. 

Indeed, research has shown that testosterone levels naturally start to head south around age 30, and then decline at a rate of one to two percent per year after age 40. The culprit, according to research published in the journal Aging Male, is a combination of decreased testicular and hypothalamic-pituitary function. 

The testicles are responsible for more than 95 percent of all overall testosterone production in men, so when they stop producing quite as much, the effects are systemic. Meanwhile, the hypothalamus and pituitary gland are two glands in the brain that support hormone production by telling the testicles when and how much T to pump out. So, any issues with these brain structures (which could be caused by anything from a concussion to an eating disorder, in addition to aging) can lead to reduced testosterone levels. 

Testosterone levels can also lull in response to lifestyle factors, such as poor sleep hygiene, chronic stress, poor nutrition, and lack of exercise, says Sun. Research has shown that testosterone levels are significantly higher in healthy older men than in older men who have a sedentary lifestyle marked by obesity, stress, and poor diet. 

Read More: These Food And Drink Habits Can Lower Your Testosterone

Testosterone levels can also tank in response to another underlying medical condition—particularly, if that condition is not diagnosed or well-managed. The presence of an underlying infection, cancer, chronic disease, kidney failure, thyroid dysfunction, and obesity, for example, can all cause low testosterone, per the National Library of Medicine. 

Where Does Testosterone Replacement Therapy Come In?

Testosterone replacement therapy is a medical treatment that involves supplementing an individual’s natural testosterone levels with artificial testosterone to restore normal levels, explains Golding-Granado. From topical gels to oral medication, needle injections to implanted pellets, there are a wide variety of administration options (more on this below) but all are designed to raise testosterone levels and reduce symptoms associated with declines. 

Most commonly, TRT is recommended for individuals who have confirmed that they have testosterone levels below 300 ng/dL through a blood test, says Sun. However, it may also be prescribed to individuals with levels well above this who are experiencing any symptoms associated with low testosterone that are negatively affecting their quality of life. Fatigue, loss of muscle mass despite regular strength training, weight gain, erectile dysfunction, and loss of libido often drive the decision to try TRT, he says. 

There is no way to know your testosterone levels or access hormone replacement therapy of any kind without a proper medical work-up, notes Golding-Granado. As such, if you’re experiencing any signs of potential low testosterone that are interfering with your quality of life or well-being, she recommends consulting with a healthcare professional. They’ll be able to discern whether your health concerns are caused by declining or low testosterone levels, or some other underlying condition. “A healthcare provider will also be able to determine the most suitable treatment and approach based on individual needs and health considerations,” she says. 

Interesting in exploring TRT? Take the questionnaire at Whole Health Rx to see if you meet initial qualifications. 

Types of Testosterone Replacement Therapy

There are nearly as many types of testosterone replacement therapy as there are symptoms that might spark an individual’s interest in it. “The choice of TRT delivery method depends on individual preferences, lifestyle, and medical considerations,” says Sun. Factors such as convenience, cost, effectiveness, and potential side effects all play a role in which is best for you.

Oral medication

Exactly what it sounds like, oral testosterone replacement therapy involves orally ingesting synthetic testosterone in capsule form. Usually taken twice daily, oral testosterone is a great option for individuals who prefer to avoid injections or minor surgery, says Sun. 

Until recently, oral T replacement wasn’t the top choice amongst healthcare providers because it had been less effective at increasing testosterone levels due to how the liver metabolizes the hormone, says Golding-Granado. However, a recently FDA-approved oral medication called Kyzatrex is shifting the story. This medication has been shown to restore testosterone levels in more than 87 percent of users, according to a 2022 study published in the Annals of Medicine & Surgery. Plus, Sun says that this new option offers the convenience of an ingestible medication without the historic concerns about liver toxicity, making it a promising prospect for many a low T-sufferer.

Gels and creams 

Another non-invasive daily option here: testosterone-containing gels and creams that are applied topically—usually to the shoulder, abdomen, or upper arm—every day, says Sun. The downside is that T-containing topicals are not always as effective at increasing testosterone levels, he says. That’s because the medication has to travel through the skin and into the bloodstream to raise levels, and efficacy is highly dependent on the exact patch of skin it’s applied to. 

There is also a risk of transferring your would-be T to others via a hug or other intimate contact, according to Sun. The National Library of Medicine notes that this transference can have harmful effects on women, especially those who are pregnant, as well as on children. You can mitigate the risk of transference by properly covering the area you applied your prescription topical to and being mindful about means of transferrence like bed-sharing. However, this may not be a mental load all people seeking TRT want to take on. 

Subcutaneous injections

Subcutaneous or intramuscular injections involve injecting synthetic hormones into your muscles either weekly or biweekly, explains Golding-Granado. This method is highly effective at raising overall testosterone levels but comes with some downsides beyond the fact that it involves giving yourself a shot (yep, it’s self-administered). Immediately following injection, testosterone levels are incredibly high, but they can drop leading up to that next injection date, Sun says. “This can result in a large difference between the peaks and valleys in your testosterone levels,” he says, which can lead to noticeable mood and energy differences, as well as libidinal changes, throughout that time. 

Pellet therapy 

Pellet therapy involves surgically implanting a rice-sized testosterone pellet in the body—usually in the buttocks—where it slowly releases testosterone into the body over the course of two to six months, explains Sun. “These offer a more hands-free approach to TRT, as they do not require a daily or weekly application, but they do require placement by a medical professional and can cause scarring with long-term use,” he says. 

The Benefits Of TRT and How Long It Takes To Experience Them

If you and your healthcare provider decide that testosterone replacement therapy is the right move for you, you might want to know what benefits you’ll experience and when. However, the timeline here depends on factors such as the type of TRT, dosage, and the individual and their overall health, says Sun. “Some patients may notice improvements in symptoms within days to weeks of starting TRT, while others may require more time to see significant changes,” he says. 

Testosterone deficiency is associated with cognitive changes and mood disturbances, such as depression and irritability, he says. As such, some of the first changes individuals often notice are mood stabilization and enhancement, and improved cognition. “Testosterone also influences libido or sexual desire,” so TRT another potential early change an individual may notice is a greater interest in sex and improved sexual function, he says. 

Read More: 5 Ways To Boost Your Testosterone Naturally

Given testosterone’s pivotal role in metabolic health, Sun says that longer-term supplementation may improve overall health, including by reducing the risk of various comorbidities like type 2 diabetes and obesity. Supplementation may also lead to improvement in other measures of health; think increased bone density, greater muscle mass, and reduced fat mass—but there is no universal timeline of when these changes occur. 

The Potential Downsides Of Testosterone Replacement Therapy

There are potential risks to testosterone replacement therapy—though the exact risks can vary based on the type of TRT used, as well as your overall health. 

“One potential side effect is the suppression of sperm production, which may lead to infertility,” says Sun. The entire endocrine system is interconnected, so when testosterone levels increase (due to TRT), the body responds by pumping out less follicle-stimulating hormone (FSH) and luteinizing hormone (LH). Both of these hormones support spermatogenesis (sperm creation), so when levels drop, sperm production does, too. If fertility is a huge concern, research suggests that short-acting methods, like daily oral medication, may be a better option compared to transdermal gels and injections, as ingestible testosterone has less of an effect on FSH and LH. 

“Testosterone replacement therapy may also cause acne and potentially lead to hair loss—especially when administered in higher doses,” shares Sun. On the acne front, the reason is that testosterone can increase the production of sebum, an oily substance produced by the sebaceous glands. If sebum production suddenly ramps up, the sebaceous glands may become clogged, which leads to acne. 

The link between testosterone therapy and hair loss is a little less direct. The short of it is that testosterone supplementation can lead to higher levels of a type of testosterone called dihydrotestosterone (DHT), which causes hair follicles to become shorter, narrower, and lighter in individuals with a genetic predisposition for balding. Genetics are thought to play a significant role here, since research hasn’t shown a significant link between TRT and hair loss in the general population.

Another significant concern—particularly with testosterone injections—is the risk of erythrocytosis, says Sun. A condition characterized by an increase in red blood cell production, erythrocytosis can make it harder for blood to travel through veins, which, in extreme cases, can lead to blood clots and even strokes, he says. If a healthcare provider becomes concerned about your risk for this condition, they may recommend donating blood to normalize levels of red blood cells, lowering your TRT dose, and/or switching modalities, he explains. 

Worth noting: Despite a long-standing belief that testosterone replacement therapy is linked with an increased risk of cardiovascular dysfunction and prostate cancer, recent research has debunked both of those myths. Indeed, one 2023 review published in The New England Journal of Medicine did not find that testosterone replacement therapy resulted in any increased cardiovascular risk. Actually, “the majority of research suggests that appropriate testosterone levels may even be cardioprotective,” says Sun. 

Across the board, working with a healthcare professional who can closely monitor your health via blood tests and other biomarkers is key, Sun shares. This helps ensure they detect any adverse effects early and guide adjustments to your treatment plan accordingly, he says. 

The Bottom Line On Testosterone Replacement Therapy 

Testosterone replacement therapy offers numerous potential benefits, such as improved mood, energy, libido, and body composition—in particular for individuals who have testosterone levels outside of normal ranges, as well as those experiencing symptoms associated with low T. 

Any individual considering TRT should weigh these potential benefits against the associated risks. “A thorough discussion with a healthcare provider can help you make informed decisions about whether TRT is the right choice for you,” says Sun.

Take the next step by visiting Whole Health Rx to find out if you may be a good candidate for TRT.