Is Long-Term Testosterone Therapy Safe? Benefits, Risks and Monitoring

Benefits, Risks and What to Expect

Medically reviewed by Dr. Timothy Mackey
Medical Director, NovaGenix Health & Wellness · Updated September 2026

Short answer: Testosterone replacement therapy (TRT) can be appropriate for long-term use in carefully selected men with confirmed hypogonadism, but it is not risk-free and it should not be treated as a set-it-and-forget-it prescription. Long-term safety depends on an accurate diagnosis, a treatment plan matched to the patient, and ongoing monitoring of symptoms, testosterone levels, blood pressure, hematocrit, prostate health, and fertility goals.

This article explains what current evidence says, what it does not prove, and what men should discuss with a physician before starting or continuing TRT.

Key Takeaways

Who Should Consider Long-Term TRT?

TRT is not diagnosed from symptoms alone. Fatigue, reduced libido, changes in body composition, poor sleep, depression, medication effects, thyroid disorders, and other medical problems can overlap with low-testosterone symptoms.

The Endocrine Society guideline recommends diagnosing hypogonadism only when a man has compatible signs or symptoms and unequivocally, consistently low testosterone concentrations. It also recommends confirming the finding with a repeat morning fasting total-testosterone measurement and evaluating the cause.

That is why an appropriate starting point is a clinical history plus properly timed low-testosterone testing—not choosing a dose before the diagnosis is clear. For background on how results are interpreted, see our guide to what testosterone test results mean.

What Benefits Can TRT Provide?

In men with confirmed hypogonadism, treatment may improve sexual symptoms, anemia in some men, bone density and lean body mass/body composition. The magnitude and timing of response vary, and not every symptom improves simply because a testosterone value rises.

A sound treatment plan therefore starts with specific goals. If the original problem does not improve after testosterone levels are corrected, the clinician should reconsider whether another condition is contributing. TRT should complement—not replace—sleep, nutrition, exercise, weight management, cardiovascular risk reduction, and treatment of other medical problems.

What Does the Evidence Say About Cardiovascular Safety?

The TRAVERSE trial enrolled 5,246 men ages 45 to 80 who had symptoms, two fasting testosterone levels below 300 ng/dL, and established cardiovascular disease or elevated cardiovascular risk. Testosterone gel was noninferior to placebo for the trial’s primary composite of cardiovascular death, nonfatal heart attack, or nonfatal stroke. This was important evidence against the idea that properly prescribed TRT automatically increases major cardiovascular events in a similar population.

That result is reassuring, but it is not a blanket guarantee for every patient, formulation, dose, or duration. Some adverse events—including atrial fibrillation, acute kidney injury, and pulmonary embolism—occurred more often in the testosterone group, and the trial’s eligibility criteria and follow-up limit how broadly its findings can be applied.

In February 2025, the FDA announced testosterone labeling changes removing cardiovascular boxed-warning language and requiring blood-pressure warnings. The agency subsequently requested updates in June 2026 to remove the age-related hypogonadism limitation of use and revise prostate safety information. Patients should discuss their product’s current labeling and monitoring with the clinician.

Practical meaning: cardiovascular risk should be assessed before treatment, blood pressure should be followed, and new chest pain, shortness of breath, neurologic symptoms, leg swelling, or an irregular heartbeat deserves prompt medical attention.

Does TRT Increase Blood Pressure?

Testosterone products can increase blood pressure. Following ambulatory blood-pressure studies, FDA required product-specific information and warnings about increased blood pressure. Removing the older cardiovascular boxed-warning language did not remove the need to monitor blood pressure.

Hypertension and other cardiovascular risk factors should be considered before treatment and during follow-up. Read our TRT and blood-pressure guide.

Does Testosterone Increase Prostate-Cancer Risk?

Testosterone and prostate health require a more precise answer than either “TRT causes prostate cancer” or “TRT has no prostate risk.”

A prespecified prostate-safety analysis of TRAVERSE followed 5,204 carefully screened men. The incidence of high-grade or any prostate cancer and several other prostate events was low and did not differ significantly between the testosterone and placebo groups. PSA increased more in testosterone-treated men, and men at higher baseline prostate risk were excluded. The findings are therefore reassuring for a screened population; they do not mean prostate assessment can be skipped.

The Endocrine Society recommends discussing prostate-cancer risk and monitoring with appropriate patients before treatment and again after treatment begins. A confirmed, significant PSA rise or an abnormal prostate examination may require urologic evaluation. Men with prostate cancer, a suspicious prostate finding, or an elevated PSA need individualized evaluation before TRT is considered.

The FDA’s June 2026 request included revisions to prostate-cancer and benign prostatic hyperplasia safety information. These labeling changes do not establish lifetime safety. The Endocrine Society’s July 2026 statement emphasizes that longer-term safety remains unestablished and that prostate cancers can develop too slowly for available trials to resolve the question fully.

For a deeper discussion, read Does Testosterone Therapy Cause Prostate Cancer?

Hematocrit and Red-Blood-Cell Monitoring

Testosterone can stimulate red-blood-cell production. For some men, hematocrit rises high enough to require a dose or formulation change, a pause in therapy, or evaluation for contributing factors such as sleep apnea, smoking, dehydration, or lung disease.

A complete blood count is commonly checked before treatment, after therapy begins, and periodically thereafter. The monitoring interval should reflect the patient’s results, formulation, risk factors, and clinical response. Read more about hematocrit levels on TRT.

TRT, Fertility and Testicular Function

External testosterone can suppress the signals from the brain and pituitary that normally support testosterone production inside the testes and sperm production. This includes suppression of LH and FSH. Sperm counts may fall substantially, and some men can become azoospermic while using TRT.

Men who may want children should discuss fertility before starting testosterone. The 2024 AUA/ASRM guideline advises against prescribing exogenous testosterone for men interested in current or future fertility. Adding hCG or another medication to continuing TRT should not be presented as reliable fertility protection; the evidence is too limited to recommend that strategy.

Fertility-conscious care may involve a different strategy, specialist input, or other medications depending on the diagnosis. No alternative guarantees preserved fertility. Our TRT and male fertility guide explains the choices and limitations in more detail.

Related options require their own assessment: hCG, clomiphene and enclomiphene versus Clomid. Clomiphene use for male hypogonadism is off-label, and enclomiphene is not an FDA-approved standalone medication. These are not do-it-yourself fertility protocols.

Other Long-Term Side Effects and Concerns

TRT can cause or worsen acne and oily skin, breast tenderness, fluid retention, changes in mood, reduced testicular volume, and sleep-related breathing problems in susceptible patients. Different formulations also have different practical risks, including skin transfer with gels and fluctuations or injection-site effects with injectable products.

The presence of a possible side effect does not automatically mean treatment must stop. It does mean the symptom should be evaluated rather than ignored or treated through unsupervised add-on medication. Our companion guide reviews the side effects of testosterone therapy in greater depth.

Administration also matters: review testosterone cypionate injections with your prescriber. Read about testosterone gels. With topical products, follow the product’s precautions to prevent transfer to other people.

Who may need to delay or avoid TRT?

According to the Endocrine Society guideline, clinicians should not start testosterone in men planning fertility in the near term or in patients with certain conditions, including prostate or breast cancer, elevated hematocrit, untreated severe obstructive sleep apnea, uncontrolled heart failure, a heart attack or stroke within the previous six months, thrombophilia, or specified prostate findings without further evaluation.

This list is not a substitute for an individualized medical assessment. Other diagnoses, medications, cardiovascular risks, urinary symptoms, and laboratory findings may also change the decision or monitoring plan.

What Should Be Monitored During Long-Term TRT?

After starting and during ongoing care

Monitoring is designed to answer four questions: Is treatment helping? Are testosterone levels in the intended range? Is it causing a problem? Does the original diagnosis or plan need to be reconsidered?

• Symptoms and goals: libido, sexual function, energy, mood, strength, sleep, and quality of life—without assuming every symptom is hormonal.
• Testosterone level: checked at an interval and timing appropriate to the formulation.
• Complete blood count: especially hemoglobin and hematocrit.
• Blood pressure and cardiovascular status: particularly because testosterone products carry blood-pressure warnings.
• Prostate assessment: based on age, baseline risk, symptoms, shared decision-making, and applicable screening guidance.
• Adverse effects: acne, swelling, mood changes, breast symptoms, urinary changes, sleep symptoms, and formulation-specific concerns.
• Fertility goals: revisited when life plans change.

The Endocrine Society recommends evaluating patients after treatment starts to assess response, adverse effects, and adherence. Follow-up timing is individualized, but it should be more frequent during initiation or dose adjustment and continue throughout therapy.

Can You Stay on TRT for Life?

Some men remain on TRT for many years because the underlying cause of hypogonadism persists. Treatment is not automatically “for life.” Continuing depends on the diagnosis, clinical response, adverse effects, fertility goals and health changes, discussed with the treating clinician.

Available studies do not establish risk-free lifetime use. See what happens after stopping testosterone for recovery considerations.

When Should TRT Be Reconsidered?

A review is appropriate when benefits are inadequate, adverse effects are significant, hematocrit rises, fertility goals change, prostate findings are concerning, cardiovascular health changes or the original diagnosis is uncertain. A normal testosterone result with persistent symptoms can point to another cause.

Discuss changes with the prescriber instead of stopping or adjusting medication on your own. Severe or sudden symptoms require prompt care.

Frequently Asked Questions

Is TRT safe to take for years?

It can be appropriate for confirmed hypogonadism with individualized care and ongoing monitoring. Treatment is not risk-free, and lifetime safety is not established.

Does TRT increase the risk of heart attack or stroke?

TRAVERSE found testosterone gel noninferior to placebo for its primary major cardiovascular endpoint in the men studied. It did not prove heart protection or eliminate other risks.

Does testosterone cause prostate cancer?

Screened trial populations have not shown a significant increase in prostate-cancer events over the study period. That does not establish lifetime safety; individualized prostate assessment remains important.

Can TRT raise hematocrit?

Yes. Increased red-cell production can raise hematocrit enough to require reassessment of treatment and contributing conditions.

Can TRT raise blood pressure?

Yes. FDA labeling includes blood-pressure warnings, and blood pressure should be considered throughout treatment.

Does TRT make you infertile?

It can substantially suppress sperm production, sometimes to zero. Fertility effects vary, and TRT is not reliable contraception or fertility-preserving treatment.

Do you have to stay on TRT forever?

No automatic rule applies. Some underlying causes persist, but continued treatment should be periodically reassessed.

What blood tests are needed while on TRT?

Testosterone and CBC/hematocrit are important. Other tests and prostate assessment depend on clinical needs, age, risk and formulation.

Can TRT worsen sleep apnea?

Sleep-disordered breathing warrants attention, particularly in susceptible patients. Untreated severe obstructive sleep apnea is a reason not to start TRT under Endocrine Society guidance.

What happens if I stop testosterone therapy?

Symptoms may return, and natural testosterone and sperm recovery vary. Plan discontinuation and follow-up with your clinician.

Have Questions About TRT and Long-Term Safety?

NovaGenix Health & Wellness provides physician-led evaluation and ongoing monitoring from Jupiter, Florida, serving Palm Beach County. A consultation can review symptoms, laboratory findings, medical history and fertility goals.

NovaGenix uses a diagnosis-first, physician-directed approach. The decision to start or continue TRT should connect symptoms, repeated laboratory findings, medical history, fertility goals, treatment response, and safety monitoring—not rely on a single number or a standardized dose.

If you are considering treatment, begin with our testosterone replacement therapy overview. If you are already using testosterone and have questions about long-term safety, changing symptoms, or laboratory results, request an individualized review rather than changing your protocol on your own.

Request a consultation with NovaGenix Health & Wellness or call 561-277-8260.

Text Us · Dr. Timothy Mackey · About NovaGenix

Medical references

1. Endocrine Society: Testosterone Therapy for Hypogonadism Guideline Resources.
2. U.S. Food and Drug Administration: Class-wide labeling changes for testosterone products, February 28, 2025.
3. Lincoff AM, et al. Cardiovascular Safety of Testosterone-Replacement Therapy. New England Journal of Medicine. 2023.
4. Bhasin S, et al. Prostate Safety Events During Testosterone Replacement Therapy in Men With Hypogonadism. JAMA Network Open. 2023.

This article is for general education and does not replace medical evaluation, diagnosis, or treatment. Individual recommendations depend on history, examination, laboratory findings, fertility goals, and other risk factors.