Testosterone replacement therapy (TRT) is a long-term treatment option for men with confirmed hypogonadism when the dose stays within the physiologic range and a clinician monitors the treatment. TRT is not risk-free, and evidence does not establish safety over a lifetime, particularly for prostate cancer and other outcomes beyond several years.

The TRAVERSE trial included 5,246 men and followed them for an average of about 33 months. In February 2025, the U.S. Food and Drug Administration removed the class-wide boxed warning about increased cardiovascular events from testosterone product labels after reviewing the trial. The FDA also required warnings about possible blood pressure increases.

TRT should not be used simply to treat normal age-related changes, improve athletic performance, or raise testosterone from a normal level. The FDA limits approved testosterone use to men with low testosterone linked to an associated medical condition.

TRT Safety at a Glance

Question Evidence-based answer
Does TRT increase heart attacks or strokes? In the TRAVERSE trial, TRT did not increase major cardiovascular events compared with placebo over an average follow-up of about 33 months.
Can TRT affect heart rhythm? Yes. Atrial fibrillation and other nonfatal arrhythmias occurred more often in the testosterone group in TRAVERSE.
Can TRT cause blood clots? TRT can increase red blood cell production, and venous thromboembolism, including pulmonary embolism, has been reported.
Does TRT cause prostate cancer? A clear short- or medium-term increase was not shown, but long-term prostate cancer safety remains uncertain.
Does TRT reduce fertility? Yes. Exogenous testosterone can suppress sperm production and may cause very low or absent sperm counts.
Is TRT safe for normal aging? TRT is not routinely recommended when testosterone is low only because of aging without confirmed hypogonadism.

What Does the Cardiovascular Evidence Show?

In the TRAVERSE trial, TRT did not increase major cardiovascular events over about 33 months among men with symptoms, testosterone levels below 300 ng/dL, and existing or elevated cardiovascular risk.

The trial found:

  • Major cardiovascular events occurred in 7.0% of men receiving testosterone and 7.3% receiving placebo.
  • Nonfatal arrhythmias requiring intervention occurred in 5.2% of the testosterone group and 3.3% of the placebo group.
  • Atrial fibrillation occurred in 3.5% of the testosterone group and 2.4% of the placebo group.
  • Acute kidney injury occurred in 2.3% of the testosterone group and 1.5% of the placebo group.
  • Pulmonary embolism occurred more often in the testosterone group.

The results suggest that medically prescribed TRT did not increase the combined risk of heart attack, stroke, or cardiovascular death in the men studied. They do not show that TRT is harmless for every person or that treatment lasting decades carries no additional risk.

The FDA label changes also left warnings about blood clots, elevated hematocrit, fluid retention, and other complications. Blood pressure should be checked before treatment and periodically afterward.

What Are the Main Long-Term Risks of TRT?

1. Elevated Hematocrit and Thicker Blood

TRT can increase red blood cell production. This is called erythrocytosis or polycythemia.

A hematocrit of 54% or higher requires intervention under Endocrine Society guidance. Treatment may need to be paused, the dose reduced, or the formulation changed. A clinician may also investigate other causes, including sleep apnea.

Regular blood tests matter because men with untreated sleep apnea, smoking-related low oxygen, lung disease, or a high baseline hematocrit may face greater risk.

2. Blood Pressure and Cardiovascular Complications

Some testosterone products can raise blood pressure. Uncontrolled hypertension should be treated before TRT begins, and blood pressure should be checked during treatment.

TRT requires extra caution in men with:

  • A recent heart attack or stroke
  • Uncontrolled heart failure
  • Significant cardiovascular disease
  • A history of blood clots
  • Atrial fibrillation or another clinically important arrhythmia
  • Uncontrolled high blood pressure

3. Reduced Fertility

Testosterone injections, gels, and other external testosterone products can suppress the brain signals that stimulate the testes. Sperm production can fall substantially or stop altogether.

TRT is not a fertility treatment. Men who want children in the near future should discuss other options with a reproductive urologist or endocrinologist before starting treatment. Stopping TRT may allow sperm production to recover, but recovery is not immediate or guaranteed in every case. FDA labeling warns that exogenous testosterone may cause azoospermia, meaning no sperm in the semen.

4. Prostate Monitoring

Current evidence has not established that appropriately prescribed TRT causes prostate cancer. The available studies have not lasted long enough to remove concern about very long-term risk. The Endocrine Society stated in 2026 that long-term safety, including prostate cancer risk, remains unestablished.

TRT can also worsen urinary symptoms in some men with benign prostatic hyperplasia. Doctors may check PSA and assess prostate cancer risk before treatment and during the first year.

A urology evaluation is recommended during the first year if PSA:

  • Rises by more than 1.4 ng/mL above baseline
  • Is confirmed above 4.0 ng/mL
  • Is accompanied by an abnormal prostate examination

5. Sleep Apnea, Acne, Breast Enlargement, and Fluid Retention

Other possible adverse effects include:

  • Worsening or triggering sleep apnea
  • Acne or oily skin
  • Breast enlargement or tenderness
  • Testicular shrinkage
  • Reduced sperm production
  • Fluid retention or swelling
  • Worsening urinary symptoms
  • Mood or libido changes when testosterone levels fluctuate substantially

The risk tends to increase when doses produce above-normal testosterone concentrations. The usual treatment goal is a testosterone level in the mid-normal physiologic range, not the highest level that can be achieved.

Who Should Avoid Starting TRT or Obtain Specialist Evaluation First?

The Endocrine Society recommends against starting TRT in men with:

  • Known or suspected prostate cancer
  • Male breast cancer
  • An unexplained prostate nodule
  • Elevated PSA requiring urological evaluation
  • Elevated hematocrit
  • Untreated severe obstructive sleep apnea
  • Severe lower urinary tract symptoms
  • Uncontrolled heart failure
  • A heart attack or stroke within the previous six months
  • Thrombophilia, a condition that increases blood clot risk
  • A plan to preserve fertility in the near term

These conditions do not always mean TRT can never be used. They mean treatment should not begin without addressing the underlying risk and deciding whether specialist input is needed.

How to Make TRT Safer Over the Long Term

A monitored TRT plan usually includes:

  1. Confirming the diagnosis. Low testosterone should generally be confirmed with at least two accurate early-morning tests, together with compatible symptoms. A single low result is not enough.
  2. Identifying the cause. Doctors may check luteinizing hormone, follicle-stimulating hormone, medications, obesity, sleep apnea, pituitary disease, testicular disease, and other possible causes.
  3. Checking baseline health. Important assessments may include hematocrit, blood pressure, PSA when appropriate, cardiovascular history, sleep apnea risk, and fertility plans.
  4. Using the lowest effective dose. Treatment should aim for a physiologic, generally mid-normal testosterone concentration.
  5. Repeating blood tests. The Endocrine Society recommends checking testosterone and hematocrit at approximately three to six months, again at 12 months, and annually afterward.
  6. Checking whether treatment is helping. If symptoms do not improve despite normalized testosterone, the diagnosis and treatment plan should be reassessed instead of automatically increasing the dose.

The Important Distinction: TRT Versus Steroid Use

Medically supervised TRT aims to restore testosterone to a normal physiologic range in someone with documented deficiency. Anabolic steroid cycles often use doses far above replacement levels and may combine testosterone with other drugs.

Evidence about prescribed TRT cannot show that high-dose bodybuilding or performance-enhancing steroid use is safe. The FDA continues to warn about testosterone abuse at doses higher than recommended and when testosterone is combined with other anabolic steroids.

Bottom Line

TRT is a monitored treatment for confirmed hypogonadism, not a general anti-aging or performance drug. The evidence is reassuring about major cardiovascular events over roughly one to four years in appropriately selected men, but it does not establish safety over decades. Treatment should follow compatible symptoms, consistently low testosterone, and a plan to monitor hematocrit, blood pressure, prostate risk, cardiovascular health, fertility, and treatment response.