A man is treated for increased red blood cell production, a TRT side effect

TRT Side Effects: Myths Vs. Facts

Some impacts are less serious than experts once believed.

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Testosterone replacement therapy (TRT) has helped millions of men with low testosterone find relief from life-dampening symptoms like fatigue, a lackluster libido, and a flagging erection. And if you’re experiencing signs of low T—or you’ve already been diagnosed with a testosterone deficiency—and are considering testosterone replacement therapy (TRT), you probably have lots of questions about what to expect, including any negative reactions to the treatment. The good news: recent research suggests there’s a lower risk of serious TRT side effects than previously believed.

For decades, there were concerns that TRT increased men’s risks for heart disease and prostate cancer. But more recent research suggests these fears may have been overblown. One meta-analysis (1) reported 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). A more recent study found that TRT significantly reduced the risk for heart attack and stroke in men with low T.

Of course, that doesn’t mean that TRT is side-effect-free. A few men report adverse side effects while on testosterone replacement therapy. The most common reaction is an increased red blood cell count (more on that below), but other side effects include:

  • Acne or oily skin
  • Worsening sleep apnea
  • Breast swelling or tenderness
  • Infertility, due to a decreased sperm count
  • Shrinkage of the testicles
  • Prostate disorders
 

No one can predict if you’ll experience TRT side effects. But knowing the potential reactions to the treatment can help you spot them early if they do happen. In some cases, your doctor may need to lower your dose or discontinue the therapy, says urologist Joshua Calvert, M.D.

Before jumping into side effects though, it’s important to understand what low testosterone is, and when you might need testosterone replacement therapy.

What is Testosterone?

Testosterone is the primary male sex hormone, and it’s responsible for regulating a variety of functions in your body, from maintaining muscle to regulating your libido. In fact, testosterone is involved in all the following, and more:

  • Regulating your sex drive
  • Red blood cell production
  • Sperm production
  • Your body’s ability to store and burn fat
  • Regulating your emotions and mood
  • Fertility
  • Mental clarity and focus
  • Maintaining bone strength
  • Maintaining energy levels

What is Low Testosterone?

Testosterone is measured in terms of nanograms per deciliter (ng/dL). During your teens and twenties, T levels peak and can be anywhere from 300 to 1,200 ng/dL.

But as you slip into midlife, T levels start to slowly slip at a rate of about 1 to 1.5 percent per year. But for an increasingly large number of men, the drop is more rapid. In fact, according to a 2020 study (2), population-wide testosterone is decreasing, with the average testosterone level in men aged 15 to 39 years old decreasing d from 605 ng/dL in 2000 to 451ng/dL in 2016—a 25 percent decrease in just 15 years.

Related: Normal Testosterone Levels By Age

If your T levels plummet and you start experiencing symptoms of low T—including exhaustion, lack of motivation, sleep disturbances, mood swings, increased belly fat, or a decreased sex drive— your doctor will likely diagnose you with hypogonadism, or low testosterone.

How Do I Know If I Have Low T?

Symptoms of low T can overlap with and mimic symptoms from a range of other conditions, from stress and anxiety to conditions like obesity and cardiovascular disease. The only way to know for sure whether your symptoms are caused by low testosterone levels is via a blood test that measures the total amount of testosterone in your body (Total T) as well as the amount of so-called free T, the type of testosterone your body uses to carry out all of the functions above.

Related: Free T vs Total T: Here’s The Difference.

Since testosterone is highest in the morning, it should be measured between 7 am and 10 am for the best results. Your doctor will suggest two tests, done on different dates (but by the same laboratory) to make sure the results are accurate.

What is Testosterone Replacement Therapy?

If your testosterone level is below 300 ng/dL and you’re having symptoms related to low T, your doctor will likely recommend and prescribe testosterone replacement therapy (TRT), says Calvert. TRT supplements the testosterone your body isn’t producing, and comes in a smorgasbord of forms, from injections to topical creams and gels to patches and dissolvable lozenges.

Whatever form of TRT you and your doctor decide is right for you, he or she will closely monitor your experience, especially within the first few months as your T levels climb and stabilize.

Keep your physician in the loop about the benefits you’re seeing—a revved-up libido, improved mood, weight loss, and better concentration are often reported—as well as any side effects that you’re noticing.

Related: How to Legally Buy Testosterone Online

Is TRT Right For You?

Worried your testosterone levels might be low? Order Hone’s at-home test today to find out.

 

TRT Side Effects

Like any medical treatment, TRT can cause side effects. Most reactions are noticed within a few months of starting therapy. If you experience any of the below TRT side effects, speak to your doctor.

Increased Red Blood Cell Production

Testosterone stimulates the production of red blood cells, which contain a protein called hemoglobin, that shuttles oxygen throughout the body.

But in some cases, TRT can cause the body to overproduce hemoglobin and hematocrit (the percentage of red blood cells in your circulation), a condition called polycythemia or erythrocytosis.

Men on TRT have up to a 315 % higher risk (3) of developing polycythemia compared to those not on TRT, possibly because testosterone increases erythropoietin (EPO), a protein that stimulates red blood cell production in the bone marrow.

When there are more red blood cells, your blood becomes thicker. If your blood becomes too thick or sticky, you are at higher risk for high blood pressure, blood clots, strokes, and heart attack, says Calvert.

If you have a history of polycythemia, be sure to tell your doctor, since TRT can worsen the condition. But anyone on TRT should routinely monitor their hematocrit to make sure it doesn’t get too high, says Calvert. Your blood level should be measured within 3-6months of starting treatment, and then annually while you’re on TRT.

If your red blood cell levels do creep up too high, there’s a fix: periodic phlebotomy, a similar process to donating blood. Removing a single pint of blood can usually bring red blood cell counts back to normal. In fact, donating blood regularly may reduce your risk of developing polycythemia. “I tell every one of my patients on testosterone replacement therapy that they should donate blood every three months because it is good for them and society,” says Calvert. However, in rare cases, polycythemia may require you to stop TRT.

Acne

After starting TRT, your energy levels and libido may make you feel like a horny high schooler again. The downside: you might also experience the kind of skin breakouts you haven’t experienced since you were a teen.

Here’s why: Your skin has glands that secrete an oily substance called sebum, which forms a protective barrier against water evaporation. Testosterone stimulates androgen receptors in these glands, telling them to ramp up sebum production. But too much sebum can cause plugged-up glands (called sebaceous hyperplasia) and breakouts on your back, shoulders, chest, and face. OTC acne treatments can usually remedy the problem.

Obstructive Sleep Apnea

TRT side effects can disrupt your slumber. Sleep disorders like obstructive sleep apnea (OSA)—a condition in which your breathing starts and stops multiple times throughout the night—can lower testosterone levels because they interrupt your body’s natural sleep cycle. Throughout the night, you cycle through two basic types of sleep: Rapid Eye Movement (REM) and Non-Rapid Eye Movement (NREM). REM sleep is critical for restoring your body and energy, and for testosterone production. Testosterone levels rise when you fall asleep and peak during your first episode of REM sleep. If you don’t get enough deep sleep, your T levels can drop.

While TRT often helps men sleep better, if you already have OSA, the treatment might aggravate the condition (4), particularly in obese men (5). According to a 2018 study in the British Journal of Urology, men on TRT had almost four percent higher risk for OSA (6).

Beyond leaving you exhausted, OSA can raise your risk for high blood pressure, heart attack, and stroke, so your doctor may suggest a different treatment for low T if you have OSA. If you’re on TRT and notice any issues with your sleep patterns, report them to your healthcare provider.

Breast Swelling or Tenderness

TRT often helps guys build muscles, so you may find that your bench press routine nets you bigger gains in the pec area than it did before treatment. But for some men, less welcome chest increases occur. In up to 25% of men (7), taking extra testosterone has the unfortunate side effect of gynecomastia—making breast tissue grow because TRT disrupts the estrogen-testosterone balance. In your body, testosterone is converted to estradiol, a form of estrogen responsible for breast enlargement. As T levels rise, an enzyme called aromatase converts more free T into estradiol, which can cause your pecs to get puffy and tender.

If you notice this side effect, your doctor can prescribe a selective estrogen receptor modulator, like tamoxifen or raloxifene, which can restrict the effects of the excess estrogen.

Lower Sperm Count

When it comes to TRT side effects, this one is important for any man who is considering starting a family. TRT can decrease the number and quality of your sperm. That’s because when your brain registers an influx of testosterone, the hypothalamus sends a signal to the pituitary gland to decrease two hormones—follicle-stimulating hormone (FSH) and luteinizing hormone (LH)—both of which are required for sperm production in your testicles.

For some men, a lower sperm count can happen quickly; others notice a more gradual decline. It all depends on how well—and fast—your body responds to the additional testosterone.

A lower sperm count does not always result in infertility but it can make it more difficult to conceive. If you go on TRT and a semen analysis shows a drastic drop in your sperm count, stopping TRT (which should only be done with your physician’s guidance) usually causes sperm counts to rise again within about a year. But for a small percentage of men, fertility doesn’t return after stopping TRT.

The American Society for Reproductive Medicine strongly recommends that TRT should not be prescribed in men who want to conceive now or in the future. Other medications, including clomiphene citrate (Clomid), can raise T levels and reduce the symptoms of low testosterone while preserving fertility.

Related: TRT and Fertility: What You Need to Know

Recent research suggests there’s a lower risk of serious TRT side effects than previously believed.

Testicle Shrinkage

Among one of the most surprising TRT side effects: testicular atrophy—in layman’s terms, their testicles shrink. Here’s why: when you go on TRT, your body believes that you have plenty of testosterone, so it dials down its production. The pituitary gland doesn’t release FSH and LH, so the testicles don’t get the message to produce sperm. As work in the sperm factory slows down, your testicles can shrink.

Testicular atrophy isn’t unhealthy in itself, but it can be distressing to see your testicles shrivel. If it bothers you, speak to your doctor. He or she may prescribe Human Chorionic Gonadotropin (HCG), a hormone that mimics LH and may prevent testicular atrophy, according to some research (8).

Prostate Cancer

Scientists have been studying potential links between TRT and prostate cancer for years, 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.

What about just the average guy? One 2005 study (9) found that TRT might increase the risk for prostate cancer. But in 2017, the National Institutes of Health concluded far-ranging research into TRT that didn’t find a conclusive link—and the study authors cautioned that more research needs to be done in this area.

If you have a history of prostate cancer and are considering TRT, discuss it with your urologist, says Calvert. They can help you decide if TRT is right for you, and if you start treatment, closely monitor you.

What About Heart Problems?

Research and clinical trials have been done to identify the link between cardiovascular disease (heart problems) and TRT. Although the results are conflicting, recent evidence (10) suggests that TRT does not cause cardiovascular disease in men receiving this hormone therapy. However, the FDA still insists testosterone labels must alert consumers of cardiovascular risks and the American College of Cardiology (ACC) and American Endocrine Society both suggest that men with a history of cardiovascular problems avoid TRT.

Generally speaking, if you have any cardiac history, see your cardiologist or primary care doctor before starting treatment, and based on a complete medical checkup; they can determine if TRT is safe for you.

The Bottom Line

The most common TRT side effects include acne, increased red blood cell production, breast swelling, and testicle shrinkage. Despite earlier concerns, TRT does not appear to cause cardiovascular disease. You should only go on TRT under the supervision of a physician, and be monitored to ensure you stay healthy and do not need additional adjustments or medication.
References:
  1. Araujo AB, Dixon JM, Suarez EA, Murad MH, Guey LT, Wittert GA. Clinical review: Endogenous testosterone and mortality in men: a systematic review and meta-analysis. J Clin Endocrinol Metab. 2011 Oct;96(10):3007-19. doi: 10.1210/jc.2011-1137. Epub 2011 Aug 3. PMID: 21816776; PMCID: PMC3200249.
  2. Lokeshwar SD, Patel P, Fantus RJ, Halpern J, Chang C, Kargi AY, Ramasamy R. Decline in Serum Testosterone Levels Among Adolescent and Young Adult Men in the USA. Eur Urol Focus. 2021 Jul;7(4):886-889. doi: 10.1016/j.euf.2020.02.006. Epub 2020 Feb 18. PMID: 32081788.
  3. Jones SD Jr, Dukovac T, Sangkum P, Yafi FA, Hellstrom WJ. Erythrocytosis and Polycythemia Secondary to Testosterone Replacement Therapy in the Aging Male. Sex Med Rev. 2015 Apr;3(2):101-112. doi: 10.1002/smrj.43. Epub 2015 Dec 2. PMID: 27784544.
  4. Kim, Sung Dong, and Kyu Sup Cho. “Obstructive Sleep Apnea and Testosterone Deficiency.” The world journal of men’s health vol. 37,1 (2019): 12-18. doi:10.5534/wjmh.180017
  5. Hoyos, C.M., Killick, R., Yee, B.J., Grunstein, R.R. and Liu, P.Y. (2012), Effects of testosterone therapy on sleep and breathing in obese men with severe obstructive sleep apnoea: a randomized placebo-controlled trial. Clin Endocrinol, 77: 599-607. https://doi.org/10.1111/j.1365-2265.2012.04413.x
  6. Cole AP, Hanske J, Jiang W, Kwon NK, Lipsitz SR, Kathrins M, Learn PA, Sun M, Haider AH, Basaria S, Trinh QD. Impact of testosterone replacement therapy on thromboembolism, heart disease and obstructive sleep apnoea in men. BJU Int. 2018 May;121(5):811-818. doi: 10.1111/bju.14149. Epub 2018 Feb 27. PMID: 29383868.
  7. Eckman A, Dobs A. Drug-induced gynecomastia. Expert Opin Drug Saf. 2008 Nov;7(6):691-702. doi: 10.1517/14740330802442382. PMID: 18983216.
  8. Lee, John Alden, and Ranjith Ramasamy. “Indications for the use of human chorionic gonadotropic hormone for the management of infertility in hypogonadal men.” Translational andrology and urology vol. 7,Suppl 3 (2018): S348-S352. doi:10.21037/tau.2018.04.11
  9. Gaylis FD, Lin DW, Ignatoff JM, Amling CL, Tutrone RF, Cosgrove DJ. Prostate cancer in men using testosterone supplementation. J Urol. 2005 Aug;174(2):534-8; discussion 538. doi: 10.1097/01.ju.0000165166.36280.60. PMID: 16006887.
  10. Miner M, Morgentaler A, Khera M, Traish AM. The state of testosterone therapy since the FDA’s 2015 labelling changes: Indications and cardiovascular risk. Clin Endocrinol (Oxf). 2018 Jul;89(1):3-10. doi: 10.1111/cen.13589. Epub 2018 Apr 14. PMID: 29486065.

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