Testosterone Replacement Therapy: Know What to Expect

It isn’t an anti-aging cure-all, but testosterone replacement therapy can be beneficial when used properly.

testosterone replacement therapy

If you've been considering testosterone replacement therapy as a fountain of youth, be realistic. Per a series of studies, supplemental testosterone had no effect on overall vitality and physical function, although it may offer benefits in terms of cardiovascular health, mood and depressive symptoms, and sexual function.

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Like many men over age 65, you feel the effects of aging. You’ve lost some pep in your step, and you’ve watched the muscle mass of your 20s and 30s dwindle. Maybe your sharp wit has dulled a bit and your sexual function isn’t what it used to be. You might blame these problems on a testosterone deficiency, or what medical experts refer to as hypogonadism. After all, you’ve probably heard about the negative effects of “low T”—and the benefits of testosterone replacement therapy.

But, don’t view testosterone replacement therapy as a hormonal fountain of youth. Rather, as a series of studies suggests, supplemental testosterone might help in some respects, but it isn’t the cure for everything that ails you in your older age. Still, the therapy is safe and effective when used in the right men and with appropriate follow-up care.

The Testosterone Trials

Typically, a man’s testosterone production begins to wane around age 40. Although research has found that testosterone replacement therapy can benefit men suffering from true hypogonadism with an identifiable cause, questions remain about whether the treatment helps older men with low testosterone due to no reason other than aging.


A testosterone deficiency (hypogonadism) may cause these symptoms:

  • Sexual: Declines in libido; erectile dysfunction
  • Body: Increased fatigue; loss of muscle and bone mass; increased body fat; swollen or tender breasts; hot flashes
  • Brain: Mood disorders; mental fogginess, impaired concentration
  • Sleep: Sleep disturbances, such as insomnia

So, the National Institutes of Health funded the Testosterone Trials (TTrials), a series of studies to determine the effects of testosterone treatment on various aspects of male aging. The trials included nearly 800 men over age 65 with testosterone levels below 275 nanograms per deciliter (ng/dl) who were treated for one year with a testosterone gel to raise their testosterone level to the mid-normal range of men ages 19 to 40.

Results from several of the studies (published Feb. 21, 2017, in JAMA and JAMA Internal Medicine) showed that, compared with placebo, testosterone replacement therapy did not improve memory or other aspects of cognitive function among men with age-related cognitive impairment, but it did increase hemoglobin levels and correct anemia from both known and unknown causes in anemic men. Also, the treatment, compared with placebo, was associated with greater increases in bone density and strength.

In earlier findings from the TTrials, supplemental testosterone resulted in increased sex drive and sexual function, and it offered some benefit in terms of mood and depressive symptoms; however, it had no effect on overall vitality and physical function (New England Journal of Medicine, Feb. 18, 2016).

“The results on diverse outcomes indicate the potential trade-offs between benefits and risks of testosterone treatment in older men,” Evan Hadley, MD, director of the National Institute on Aging’s Division of Geriatrics and Clinical Gerontology, said in a statement. “However, clarifying the effects of testosterone on many major clinical outcomes, such as cardiovascular events, fractures, and disability, will require longer, larger-scale trials. The results also illustrate that decisions about testosterone treatment need to be individualized, taking into account each patient’s balance of risks for the various conditions that testosterone treatment could affect.”

Cardiovascular Questions

In 2015, the U.S. Food and Drug Administration recommended label changes to testosterone products to indicate potential cardiovascular risks, based, in part, on two analyses that found an increased risk of cardiovascular events associated with TRT. The study findings prompted some physicians to stop testosterone replacement therapy, even among some men who were successfully treated with testosterone. However, some experts cited limitations and flaws in those studies, while also pointing to evidence that testosterone replacement therapy might have a positive effect on cardiovascular health.

In the TTrials, among 138 men, use of supplemental testosterone was associated with an increase in the volume of noncalcified plaque in the coronary arteries (an early indicator of increased cardiovascular risk), but no major cardiovascular events occurred in either the treatment or placebo groups, the study found.

And, in a separate study published concurrently with the TTrials in JAMA Internal Medicine, researchers compared the cardiovascular effects of testosterone among 8,808 men who had ever received testosterone replacement therapy and 35,527 men never treated with it. They found that use of the therapy, vs. non-use, was associated with a lower risk of adverse cardiovascular outcomes over an average follow-up period of nearly 3½ years.

Use Testosterone Wisely

Although medical societies have yet to reach a consensus on a testosterone level below which testosterone replacement therapy should be started, many experts recommend that treatment be considered for men with levels below 320 nanograms per deciliter (ng/dl) who have clinical symptoms that can be attributed to hypogonadism (see sidebar for warning signs of low testosterone).

Your physician should first determine whether your symptoms arise from hypogonadism or from other factors. For example, obesity, type 2 diabetes, obstructive sleep apnea, and chronic lung, kidney, or liver disease may cause declines in testosterone, as may long-term use of opioid pain relievers (hydrocodone and oxycodone are examples) or corticosteroid drugs, such as prednisone. Addressing these underlying causes may improve your testosterone level and symptoms so that you don’t need supplemental testosterone.

If your situation warrants it, your physician may recommend a blood test to measure your testosterone. Since testosterone levels are highest in the morning and wane during the day, testing must be done first thing in the morning. Any low reading should be confirmed by a follow-up test administered several days later.

Your doctor also should order testing to confirm whether your hypogonadism originates in the testicles or in the brain. Before starting testosterone replacement therapy, you should undergo a bone-density scan, screening for prostate cancer and sleep apnea, and a measurement of your hematocrit, the percentage of red blood cells in your blood. Testosterone treatment generally is not recommended for men with a hematocrit above 54, a significantly enlarged prostate, poorly controlled heart failure, severe sleep apnea, or those who still want to father children.

Studies suggest that many men are given testosterone replacement therapy to address symptoms, despite having testosterone levels in a normal range or never having their testosterone level measured. In some cases, men may remain on the treatment for years because of an initial low testosterone measurement but are never monitored to see if their levels increase or their symptoms improve. So, be sure to follow up with your physician to make sure the treatment is working—and working safely—for you.

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Jim Black

Jim Black has served as executive editor of Cleveland Clinic’s Men’s Health Advisor newsletter since 2005. He has written about prostate diseases, men’s health, cardiovascular disease, cancer, and a wide … Read More

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