When taken under a physician’s supervision, most are pretty mild
Testosterone replacement therapy (TRT) has helped millions of men with low testosterone find relief from symptoms like fatigue, lackluster libido, and erectile dysfunction. If you’re experiencing signs of low testosterone—or have been diagnosed with a testosterone deficiency—you likely have questions about what to expect from testosterone replacement therapy (TRT), including what side effects you might experience.
Recent research suggests a lower risk of serious side effects from TRT than previously believed (1). For many men, the benefits of treating low testosterone symptoms outweigh the downsides. Still, like any medical treatment, TRT can cause side effects, usually within a few months of starting therapy. Some may resolve over time, while others may require counter medication or a dose adjustment. Some side effects may permanently affect the body, such as infertility (2, 3).
We compiled the most up-to-date research on TRT side effects in men—and advice for what to do if you experience them. While men on TRT often discuss the side effects of their medication in online forums or videos, only some of these side effects are genuinely studied and understood. Not every side effect listed below is backed by science. However, we address the side effects that come up most often in a conversation, fact-checking the accuracy of those claims against academic journals and medical publications.
It’s impossible to predict if you’ll experience side effects from TRT. But knowing what to look for can help you get treated quickly. If you experience any side effects, talk to your doctor, says urologist Joshua Calvert, M.D. The most common TRT side effect for men is an increased red blood cell count, but other side effects of testosterone replacement therapy include:
Testosterone replacement therapy stimulates the production of red blood cells. These cells contain a protein called hemoglobin, which transports oxygen throughout the body. If too many red blood cells are produced, it can lead to a condition called polycytosis (4).
Men on TRT face a 315 percent higher risk of developing polycythemia compared to those not on TRT (5). This may be because testosterone increases erythropoietin (EPO), a protein that signals your bone marrow to churn out more red blood cells. While having robust oxygen delivery can sound great, thicker blood puts you at higher risk for high blood pressure, blood clots, strokes, and heart attack, says Calvert.
TRT generally improves mood, but in some men, they may feel depressed. Depression usually occurs in the beginning stages of treatment as a result of your estrogen levels being too high (6). Talk to your doctor if you’re feeling depressed. They can adjust the estrogen level in your treatment.
Feeling irritable or angry is another potential side effect of TRT in men. However, a study published in Psychoneuroendocrinology, found that increases in the thyroid hormone thyroxine, not testosterone, were linked to anger (7).
Breast growth and nipple sensitivity are relatively common among men on TRT. About 25 percent of men on TRT develop breast tissue growth, called gynecomastia (8). Here’s why: As noted above, when you’re on TRT, some testosterone is converted to estradiol, a form of estrogen responsible for breast tissue growth. As estradiol levels rise, an enzyme called aromatase converts more free testosterone into additional estradiol, which can cause your pecs to get puffy and tender. The first sign of gynecomastia tends to be itchy nipples.
Your skin contains glands that secrete an oily substance called sebum, which forms a protective barrier against water evaporation. TRT stimulates androgen receptors in these glands, telling them to ramp up sebum production. The glands can sometimes become plugged, resulting in breakouts, especially on your back, shoulders, chest, and face. Over-the-counter acne treatments can help.
Testosterone levels rise when you fall asleep each night and peak during your first episode of REM sleep. If you have sleep apnea, repeated night wakings can prevent you from reaching the deeper stages of sleep that are critical for testosterone production. While taking TRT might seem like the solution, adding testosterone might aggravate existing sleep apnea, especially if you’re obese (9). According to a 2018 study in the British Journal, men on TRT were at an almost four percent higher risk for sleep apnea (10). Beyond leaving you exhausted, the condition can raise your risk for high blood pressure, heart attack, and stroke. A continuous positive air pressure (CPAP) machine can help (9).
TRT can suppress sperm production and, therefore, cause infertility. A lower sperm count doesn’t always result in infertility, but it can make it more difficult for men to conceive (11). When your brain registers an influx of testosterone, it tells the hypothalamus to dial down two hormones FSH and LH—that trigger sperm production in your testicles.
For some men, the drop in sperm count from TRT happens quickly; others notice a more gradual decline. If a semen analysis shows a drastic drop in your sperm count, stopping TRT under your physician’s guidance will usually cause them to rise again within about a year.
But for a small percentage of men, fertility doesn’t return after stopping TRT (11). If you’re considering a family, medications like clomiphene citrate can treat symptoms of low testosterone without impacting fertility.
Clinical trials linking cardiovascular disease and TRT have shown conflicting results—which is why listing cardiovascular disease as a side effect is hotly debated (12). For decades, research suggested TRT could increase men’s risks for heart disease and prostate cancer. However, a meta-analysis in 2011 revealed that men who had been on TRT for more than 16 months had a lower risk for cardiac events and prostate cancer than men who had been on it for less time (or not at all) (13).
Three years later, another study confirmed that TRT significantly reduced the risk of heart attack and stroke in men with low testosterone (2). In 2023, a double-blind clinical trial (TRAVERSE trial) showed no short-term differences in cardiovascular adverse events with TRT in aging men with pre-existing cardiovascular disease (1).
Still, the FDA requires all testosterone products to have a label warning consumers of potential cardiovascular risks. The American College of Cardiology and the American Endocrine Society suggest that men with a history of cardiovascular problems avoid TRT (14).
If you have a history of cardiac disease, mention it to your physician. They can do a complete medical checkup to determine if TRT is safe for you.
An oral form of testosterone called C-17 alkylated androgen steroids may have liver-related concerns. When taken, this formulation of TRT can stress the liver and potentially lead to liver cancer, liver disease, or liver failure. Jaundice, where your skin can turn a yellow tint, is another reported side effect (2).
If you already have chronic liver disease, experts recommend testosterone cream or gel instead of injections, as research suggests they pose little risk of liver toxicity or disease. In one 2011 study, 16 men with liver cirrhosis were given a gel form testosterone therapy for 6 months. At the end of the treatment, their free testosterone levels had risen, and there was no evidence of liver damage (15).
Research from an animal study in 2015 also suggests that TRT—specifically the estrogen it produces—may help protect against non-alcoholic fatty liver disease (NAFLD) (16). According to the researchers, estrogen may block the production of fatty acids and cholesterol while boosting blood oxidation—essentially putting the breaks on liver disease before it starts (17). Still, researchers say more studies are needed to draw a direct correlation between TRT and a reduced risk of liver disease (16).
Extra testosterone in body fat converts into smaller molecules—like 17 beta-estradiol, a form of estrogen known as E2 (18). While estrogen is essential (yes, even for men), too much of it—especially if not balanced with progesterone—can lead to health issues (18).
Some studies have linked elevated estrogen levels from TRT to higher rates of heart attack and stroke (2). High levels of estrogen can also cause breast growth (gynecomastia), infertility, and erectile dysfunction (2).
That said, researchers quickly note that these outcomes vary; factors like age, dose, and overall health also play a large role (2). Your physician should monitor your estrogen levels to ensure they’re not getting too high. They can adjust your treatment plan to get them into a normal range if they become elevated.
TRT can cause testicular atrophy—aka testicular shrinkage. When you’re on TRT, your body believes that you have plenty of testosterone, so it dials down its natural production. When this happens, your pituitary gland releases less follicle-stimulating hormone (FSH) and luteinizing hormone (LH), the hormones that trigger sperm production (16). When your testicles produce less sperm, they shrink. The good news? While it can be jarring to see, testicular atrophy isn’t unhealthy or dangerous. Some research suggests that Human Chorionic Gonadotropin (HGC) prevents testicular atrophy (8).
Scientists have been studying potential links between TRT and prostate cancer for decades, and the research is still ongoing, says Calvert.
“There’s a concern that in metastatic prostate cancer—cancer that started in the prostate—that the cancer cells are being fed by testosterone,” Calvert explains. Metastatic prostate cancer is relatively rare, says Calvert, and men who are diagnosed with it are usually prescribed testosterone blockers.
One 2005 study found TRT might increase the risk of prostate cancer (19). However, a 2013 analysis of data from 150,000 older men (half on TRT, half not) found no significant difference in prostate cancer rates between the groups (20). More recent research, including a 2023 TRAVERS study, found no significant difference in prostate cancer incidences between men who received TRT and men who didn’t.
In addition to the common side effects, it’s essential to understand other health issues that may arise for men taking TRT. Some side effects include skin and facial hair issues, hair loss, fatigue, and water retention.
Transdermal TRT patches that stick directly to your skin can irritate people allergic to adhesives, leading to itchiness, redness, or irritation. When your skin absorbs testosterone, it can cause burning or swelling (21). Tell your doctor if you experience any of these skin side effects from TRT.
A few months into TRT treatment, some men experience facial hair growth, while others notice no change. Why the difference? A testosterone byproduct called Dihydrotestosterone (DHT) governs hair growth. Enzymes in your hair follicles convert testosterone into DHT, which signals those follicles to grow (22).
DHT—the same hormone that can jumpstart facial hair growth—can cause hair loss on your head. If you’re genetically prone to male-pattern baldness (take a look at the men in your family for clues), you may see thinning or shedding once you begin therapy. Rather than fueling new growth, DHT builds up around hair follicles and puts the brakes on hair production. Medications like finasteride and minoxidil can prevent extensive hair loss for men on TRT.
TRT usually helps restore hormonal balance, improving energy levels, mood, and overall well-being. However, some men report feeling fatigued after taking TRT. One small study of 63 men—half on TRT and half not—found those on testosterone therapy reported less fatigue over a year (23).
When you start TRT, you may retain water because the hormone is easily converted into estrogen in the body. These high estrogen levels can boost antidiuretic hormone production, which tells the kidneys how much salt and water to absorb or release in your blood (24). You may notice a temporary rise in the number on your scale, but it’s not weight gain (TRT is linked to weight loss, not gain). Generally, water retention due to TRT isn’t a concern unless you’ve been diagnosed with heart failure (25). Usually, this means your kidneys are already struggling to regulate the water and sodium in your body. Going on TRT will only exacerbate this issue.
Source: Hone Health
If you’re experiencing any frustrating or concerning TRT side effects, contact your doctor. After meeting to discuss your treatment plan, your doctor may adjust your dose or delivery system (switching from testosterone injections to cream, for example) or switch you to a different medication.
If your testosterone deficiency is mild, your doctor may suggest you stop using TRT and consider natural methods—like exercise or supplements—to increase your testosterone levels and ease symptoms.
To treat estrogen-related side effects, your doctor can prescribe an estrogen blocker like clomiphene citrate or an aromatase inhibitor like anastrozole to curb the conversion of testosterone into estrogen.
TRT helps millions of men get relief from low testosterone symptoms, increasing their energy, sex drive, and confidence. However, like any medication TRT is accompanied by side effects that affect some men more than others, including mood swings, breast growth, acne, sleep apnea, and testicular atrophy.
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