The Risks of Testosterone Replacement Therapy (TRT) – What’s Real, What’s Overstated, and What Actually Matters

Testosterone Replacement Therapy (TRT) can meaningfully improve quality of life for men with clinically confirmed testosterone deficiency. But it is not risk-free. The goal of this article is to explain the risks honestly – without fearmongering, and without minimizing what matters.

A responsible decision about TRT is always a risk-benefit conversation that depends on your symptoms, your lab results, your overall health, and how closely therapy is monitored. Medical guidelines emphasize that TRT should be prescribed for men with both consistent biochemical evidence of low testosterone and relevant symptoms – not simply “for aging.”^{1, 4}

1) Fertility and suppression of natural testosterone production

When you take external testosterone, your brain reduces signals (LH/FSH) that normally stimulate the testes. In practical terms, TRT can suppress your body’s own testosterone production and can reduce sperm production.¹

If fertility matters to you (now or later), this is one of the most important topics to discuss before starting TRT. Good clinicians plan for this and explain options based on your situation rather than ignoring it.

2) Elevated hematocrit (thicker blood) and why monitoring matters

Testosterone can increase red blood cell production. In some men, this raises hematocrit to levels that may increase risk if left unmanaged. Because of this, major guidelines recommend checking hematocrit at baseline and periodically during treatment.^{1, 2}

This is not a “rare technicality.” It is one of the most common safety issues clinicians actively watch on TRT. If a provider is not monitoring hematocrit, that is a red flag.

3) Blood pressure effects (a newer emphasis in labeling)

In February 2025, the FDA announced class-wide labeling changes for testosterone products after reviewing ambulatory blood pressure monitoring studies and the large TRAVERSE trial. The FDA’s update adds or strengthens warnings about increased blood pressure for products that did not already include them.³

Practically, this means blood pressure should be treated as a real monitoring variable during TRT – especially if you already have hypertension, sleep apnea, or cardiovascular risk factors.

4) Cardiovascular risk: what the best evidence actually says

Cardiovascular safety is the most argued-about TRT topic online. A key reason is that older studies produced mixed signals and were often interpreted without nuance. In 2023, the TRAVERSE randomized trial (published in The New England Journal of Medicine) found testosterone therapy was noninferior to placebo for major adverse cardiovascular events in a high-risk population of men with documented hypogonadism, when used as indicated and monitored.⁵

That said, TRAVERSE also observed higher rates of certain adverse events (including atrial fibrillation and pulmonary embolism) in the testosterone group, which matters for individual risk assessment and monitoring.⁵

Bottom line: properly prescribed TRT does not appear to increase major cardiovascular events overall in the TRAVERSE population, but it still requires individualized screening and ongoing monitoring.

5) Estradiol (estrogen) imbalance – both too high and too low can be a problem

Some testosterone converts to estradiol. Estradiol is not “bad” – it supports bone health, sexual function, and mood. Problems usually come from imbalance (either direction), often driven by dosing that is too aggressive or by poor follow-up.

This is why clinical practice guidelines emphasize structured monitoring for adverse effects and lab values rather than treating TRT as a set-it-and-forget-it prescription.¹

6) Lipids (cholesterol) and metabolic markers

TRT can affect lipid markers in some individuals. The direction and size of the effect varies based on baseline health, formulation, dose, and lifestyle. This is a major reason reputable protocols keep an eye on cardiometabolic health over time rather than focusing only on testosterone numbers.¹

7) Acne, skin changes, and hair-related effects

Acne and oily skin can occur, especially early in treatment or when dosing is higher than needed. Hair-related effects are highly individual and influenced by genetics. These are usually quality-of-life risks, not medical emergencies, but they should still be discussed honestly.

8) Prostate and PSA: what monitoring is for

TRT is not considered a proven cause of prostate cancer, but testosterone can stimulate prostate tissue activity. Guidelines recommend assessing prostate cancer risk and monitoring PSA in appropriate patients, especially during the first year of therapy, using shared decision-making based on age and risk profile.^{1, 2}

This is one of the reasons “TRT without labs” is a bad idea. Monitoring is not optional if your goal is long-term safety.

Who should be extra cautious (or may not be a candidate)

TRT is not appropriate for everyone. Major guidelines outline contraindications and caution zones that require physician evaluation rather than self-treatment. Examples include certain prostate cancer situations, markedly elevated hematocrit, and other conditions where risk may outweigh benefit.¹

The biggest risk is poorly managed TRT

The most preventable problems with TRT come from bad process: starting without proper diagnosis, using excessive dosing, skipping follow-up labs, or reacting to side effects without clinical context.

Evidence-based guidelines emphasize standardized monitoring – including symptoms, testosterone levels, hematocrit, and prostate risk assessment – especially early in therapy.^{1, 2}

A balanced conclusion

TRT is neither a miracle nor a menace. It is a medical therapy that can be highly beneficial for the right patient, and risky for the wrong patient or when done without appropriate oversight.

If you’re considering TRT, the smartest question is not “Is TRT safe?” It’s “Is TRT appropriate for me – based on symptoms, repeat labs, and a plan for long-term monitoring?”

References

References

1. Endocrine Society Clinical Practice Guideline (2018) – Testosterone Therapy for Hypogonadism
2. American Urological Association (AUA) Guideline – Testosterone Deficiency Guideline
3. U.S. FDA (Feb 28, 2025) – Class-wide labeling changes for testosterone products
4. U.S. FDA Drug Safety Communication (Mar 3, 2015) – Cautions about use for age-related low testosterone and labeling changes
5. Lincoff AM, et al. (2023). Cardiovascular Safety of Testosterone-Replacement Therapy (TRAVERSE). New England Journal of Medicine