Testosterone Replacement Therapy Myths, Debunked: What the Research Actually Says Summary
- TRT does not cause prostate cancer — the largest randomized trial to date found no significant difference in PCa incidence compared to placebo, which helps dispel one of the common Testosterone Replacement Therapy Myths.
- Current evidence, including the TRAVERSE trial, shows TRT does not raise heart attack or stroke risk in hypogonadal men.
- Newer oral testosterone formulations bypass the liver entirely and are not associated with hepatotoxicity.
- Real risks — elevated red blood cell count, fertility suppression, blood pressure changes — exist and require monitoring. They are not, however, reasons to avoid TRT in men who need it.
Introduction: A Treatment Buried Under Myths
Few treatments in men’s health carry more misinformation than testosterone replacement therapy. Physicians hesitate to prescribe it. Patients hesitate to ask for it. Moreover, many men who have genuine testosterone deficiency go untreated for years — not because the evidence is against therapy, but because the myths have grown louder than the data. The 2018 American Urological Association guidelines acknowledged that a large proportion of men who need testosterone therapy remain untreated, primarily because of clinician concerns around prostate cancer and cardiovascular events (Mulhall et al., 2018).
The most common testosterone replacement therapy myths follow a predictable pattern: TRT causes prostate cancer, TRT triggers heart attacks and strokes, oral testosterone destroys the liver, there is one clean threshold for diagnosing low T, and over-the-counter testosterone boosters offer a safer path. Each of these claims has shaped clinical practice in ways that the current evidence simply does not support.
That said, real risks do exist — and they matter. Testosterone therapy can raise red blood cell count, which may elevate blood pressure and, in some cases, cardiovascular risk. It suppresses the body’s own hormone production and can suppress sperm production. Sleep apnea can worsen in susceptible men. Gynecomastia and fluid retention are documented adverse effects. And the potential for misuse — by men obtaining testosterone without clinical oversight — represents a genuine public health concern. These are not myths. They are documented consequences that require appropriate monitoring, appropriate patient selection, and honest clinical conversations.
Testosterone Replacement Therapy Myths and Real Risks Worth Knowing
The problem, therefore, is not that testosterone therapy is risk-free. The problem is that the most feared risks — cancer, heart attacks, liver failure — are either unsupported or substantially overstated by the current evidence. Meanwhile, the real, manageable risks often go underdiscussed precisely because clinicians are too busy managing the imaginary ones.
In a 2025 review published in Sexual Medicine Reviews, Khera and colleagues at Baylor College of Medicine, the University of Utah, and Miriam Hospital conducted a structured literature search of PubMed, Embase, and CINAHL, drawing from 47 included studies to systematically address five major testosterone replacement therapy myths. The review was funded by Tolmar, Inc., a manufacturer of oral testosterone undecanoate products — a conflict of interest worth keeping in mind. Here is what the evidence shows.
Testosterone Replacement Therapy Myth 1: TRT Causes Prostate Cancer
The fear that testosterone fuels prostate cancer traces back to early 20th-century observations that castration slowed cancer growth in some patients. Decades later, that foundational reasoning has largely collapsed under the weight of contradictory data.
The 2018 AUA guidelines state explicitly that there is no evidence TRT increases prostate cancer risk (Mulhall et al., 2018). The largest randomized trial of TRT conducted to date enrolled 5,246 men with hypogonadism and found no significant difference in prostate cancer incidence between the TRT and placebo groups — 0.2% vs. 0.1% for high-grade PCa, P=0.51 (Bhasin et al., 2023). A 2014 meta-analysis of 22 randomized trials (n=2,351) reached the same conclusion (Cui et al., 2014).
Furthermore, several studies suggest TRT may be safe — and potentially beneficial — for men treated for localized prostate cancer. A 2016 cohort study of 10,311 men found that long-term TRT was associated with reduced PCa mortality (Wallis et al., 2016). A 2020 retrospective study (n=850) found TRT significantly reduced biochemical recurrence after radical prostatectomy, though the authors noted these findings require confirmation in prospective trials (Ahlering et al., 2020).
One important caveat: the landmark 2023 trial excluded men with PSA above 3 ng/mL, so these results do not apply to men at high PCa risk. Complex cases still warrant specialist involvement.
Myth 2: TRT Raises Heart Attack and Stroke Risk
This misconception has regulatory weight behind it. In 2014, Health Canada issued a warning about a possible association between TRT and increased cardiovascular risk. The following year, the FDA mandated that labels for all testosterone products include a warning against the possible increased risk of heart attacks and strokes, citing four studies that suggested elevated CV risk with TRT — though the strength of that evidence was described as weak (Khera et al., 2025). The European Medicines Agency, notably, conducted its own independent review and declined to add the warning.
The evidence since then has moved substantially in the other direction. The TRAVERSE trial — the largest prospective cardiovascular outcomes study of TRT to date — enrolled men with hypogonadism and established heart disease or high CV risk. It found no difference in MACE (major adverse cardiovascular events) between the TRT and placebo groups (Lincoff et al., 2023). A 2024 meta-analysis of 26 randomized trials (n=10,941) confirmed that TRT does not worsen cardiovascular outcomes or increase mortality risk in hypogonadal men (Sood et al., 2024).
Additionally, a review of over 200 studies on testosterone and cardiovascular disease found that only four suggested increased risk, while several dozen found that normal T levels benefited CV health and mortality (Morgenthaler et al., 2015). A prospective cohort meta-analysis published in Annals of Internal Medicine found that men with low T had significantly higher rates of all-cause and cardiovascular death (Yeap et al., 2024).
Low testosterone, in other words, may itself be the cardiovascular risk factor — not the treatment for it.
That said, TRT can elevate red blood cell production, which in turn may raise blood pressure in some men (Khera et al., 2025). Clinicians should assess baseline cardiovascular risk, confirm blood pressure is controlled before initiating TRT, and monitor both throughout treatment.
Myth 3: All Oral Testosterone Formulations Damage the Liver
This concern has a legitimate pharmacological basis — in older formulations. Methyltestosterone (Android, METHITEST, and Testred — the latter now discontinued in the US) causes hepatotoxicity because it undergoes direct first-pass metabolism in the liver following ingestion, generating oxidative stress through its methylated structure (Khera et al., 2025).
Newer formulations work differently. Testosterone undecanoate (JATENZO, TLANDO, KYZATREX) is a non-methylated prodrug that uses a lymphatic delivery system, bypassing the liver entirely. A two-year study of oral testosterone undecanoate found no clinically significant changes from baseline in liver function tests (Honig et al., 2022). The hepatotoxicity concern that applies to methyltestosterone simply does not apply to these newer formulations.
Men who want the convenience of an oral option — avoiding clinic visits for injections — should not be steered away on the basis of outdated data.
Myth 4: There Is a Universal Definition of Low Testosterone
You might assume a hormonal diagnosis rests on a clean threshold. It does not. The FDA defines hypogonadism as a morning serum T below 300 ng/dL (average of two separate draws). The AUA uses the same T cutoff but also requires clinical symptoms. The Association of Family Practitioners cites a normal lower limit of 250–350 ng/dL. And the Endocrine Society guidelines state that the exact threshold below which symptoms occur and treatment improves outcomes “is not known” (Khera et al., 2025).
This inconsistency has real clinical consequences. T levels decline naturally with age, so age-specific thresholds may be more appropriate than a single universal cutoff. More importantly, the primary goal of TRT is symptom relief, not hitting a specific lab number. If a patient feels fully restored at T = 325 ng/dL, there is no clinical reason to push for 900 ng/dL (Khera et al., 2025).
Diagnosis should combine lab values with clinical symptoms: fatigue, decreased libido, mood changes, erectile dysfunction, and reduced physical performance, among others.
Myth 5: OTC Testosterone Boosters Are a Safe, Natural Alternative
Many men self-treat with over-the-counter “T boosters,” drawn in by the assumption that natural supplements carry fewer risks than prescription therapy. The data does not support this assumption.
A study of 50 commercially available T booster supplements found that only 25% had any data supporting T-boosting claims, and 10% contained ingredients associated with a negative effect on testosterone levels (Clemesha et al., 2020). The FDA explicitly states that supplements are not intended to treat or prevent diseases. Furthermore, several supplement ingredients carry documented interactions with other medications (Khera et al., 2025).
The “natural” label is not a safety guarantee. Men with genuine testosterone deficiency deserve regulated, clinically supervised treatment — not a product with a 10% chance of making things worse.
Practical Takeaway Summary
- TRT and prostate cancer: The evidence is clear — no causal link. Monitor PSA at baseline and during treatment, and involve a specialist for complex cases (PSA >3 ng/mL).
- TRT and cardiovascular risk: The best current evidence, including the TRAVERSE trial, shows no increased MACE risk. Low T may itself raise CV risk. Still, assess baseline CV health before starting.
- Oral testosterone and the liver: The hepatotoxicity concern applies only to methyltestosterone. Newer oral testosterone undecanoate formulations are safe for the liver.
- Diagnosing low T: Combine lab values (two early morning draws) with clinical symptoms. Aim for symptom relief, not a target number.
- OTC T boosters: Only 25% have any supporting data. Skip them.
- What actually needs monitoring: Hematocrit, hemoglobin, blood pressure, PSA, lipid profiles, and subjective symptom response at 3 months and again at 6 months, then annually.
Frequently Asked Questions Testosterone Replacement Therapy Myth
Does testosterone replacement therapy cause prostate cancer?
Testosterone replacement therapy does not cause prostate cancer, according to current evidence. The largest randomized trial of TRT to date — 5,246 men — found no significant difference in prostate cancer incidence between TRT and placebo groups (Bhasin et al., 2023). The 2018 AUA guidelines explicitly state that TRT does not increase PCa risk. Men with high PCa risk (PSA >3 ng/mL) were excluded from that trial, so individualized clinical judgment still applies in complex cases.
Can testosterone replacement therapy cause a heart attack?
Based on current evidence, testosterone replacement therapy does not raise heart attack risk in appropriately screened men. The TRAVERSE trial — the largest cardiovascular outcomes trial of TRT — found no increased MACE risk, including in men with pre-existing heart disease (Lincoff et al., 2023). A 2024 meta-analysis of 26 randomized trials (n=10,941) confirmed TRT does not worsen cardiovascular outcomes or increase mortality (Sood et al., 2024). Clinicians should still monitor blood pressure and cardiovascular health throughout treatment.
Are oral testosterone pills bad for your liver?
Older oral formulations like methyltestosterone are associated with liver toxicity due to first-pass metabolism. However, newer oral testosterone undecanoate products (JATENZO, TLANDO, KYZATREX) use a lymphatic delivery system that bypasses the liver entirely. A two-year study found no meaningful changes in liver function with these formulations (Honig et al., 2022). The hepatotoxicity concern does not apply to modern oral TRT options.
Frequently Asked Questions-Cont.
What testosterone level is considered low?
There is no single universally agreed-upon testosterone level for diagnosing low T. The FDA uses a threshold below 300 ng/dL (on two separate morning draws). The AUA requires that threshold plus symptoms. The Endocrine Society states the exact cutoff “is not known.” Practically, diagnosis should incorporate both lab values and clinical symptoms — fatigue, low libido, mood changes, and erectile dysfunction — because the goal of TRT is symptom relief, not a specific number.
Do testosterone booster supplements actually work?
Testosterone replacement therapy myths often push men toward OTC supplements, but the data is discouraging. A study of 50 commercially available T booster products found only 25% had evidence supporting their claims, and 10% contained ingredients associated with lowering testosterone levels (Clemesha et al., 2020). The FDA does not approve supplements for treating hormone deficiency. Men with genuine hypogonadism are better served by clinically supervised, regulated therapy.
Does TRT affect fertility?
Yes — and this is a documented, real concern, not a myth. Testosterone replacement therapy suppresses the body’s natural LH signal and can suppress sperm production. Men who want to preserve fertility should discuss alternatives such as clomiphene citrate or human chorionic gonadotropin (hCG) with their physician, or bank sperm before initiating TRT (Khera et al., 2025).
What are the real risks of TRT?
The real risks of testosterone replacement therapy include elevated red blood cell count (which can raise blood pressure and clotting risk), worsening of sleep apnea, suppression of natural testosterone production and fertility, and — in some men — gynecomastia or fluid retention. These are manageable with appropriate monitoring. The frequently feared risks — prostate cancer, heart attacks, liver damage — are largely unsupported by current evidence when newer formulations are used in properly screened patients (Khera et al., 2025).
References
Ahlering, T. E., My Huynh, L., Towe, M., et al. (2020). Testosterone replacement therapy reduces biochemical recurrence after radical prostatectomy. BJU International, 126(1), 91–96. https://doi.org/10.1111/bju.15042
Bhasin, S., Travison, T. G., Pencina, K. M., et al. (2023). Prostate safety events during testosterone replacement therapy in men with hypogonadism: a randomized clinical trial. JAMA Network Open, 6(12), e2348692. https://doi.org/10.1001/jamanetworkopen.2023.48692
Clemesha, C. G., Thaker, H., & Samplaski, M. K. (2020). ‘Testosterone boosting’ supplements composition and claims are not supported by the academic literature. World Journal of Men’s Health, 38(1), 115–122. https://doi.org/10.5534/wjmh.190043
Cui, Y., Zong, H., Yan, H., & Zhang, Y. (2014). The effect of testosterone replacement therapy on prostate cancer: a systematic review and meta-analysis. Prostate Cancer and Prostatic Diseases, 17(2), 132–143. https://doi.org/10.1038/pcan.2013.60
Honig, S., Gittelman, M., Kaminetsky, J., et al. (2022). Two-year analysis of a new oral testosterone undecanoate (TU) formulation in hypogonadal men: efficacy, impact on psychosexual function, and safety. Journal of Sexual Medicine, 19(12), 1750–1758. https://doi.org/10.1016/j.jsxm.2022.09.002
Khera, M., Hotaling, J. M., & Miner, M. (2025). Testosterone deficiency and treatments: common misconceptions and practical guidance for patient care. Sexual Medicine Reviews, 13(3), 373–380. https://doi.org/10.1093/sxmrev/qeaf011
Lincoff, A. M., et al. (2023). TRAVERSE trial — Cardiovascular safety of testosterone replacement therapy in hypogonadal men. New England Journal of Medicine. [Full citation not extractable from source; verify via DOI at NEJM.org]
References
Morgenthaler, A., Miner, M. M., Caliber, M., Guay, A. T., Khera, M., & Traish, A. M. (2015). Testosterone therapy and cardiovascular risk: advances and controversies. Mayo Clinic Proceedings, 90(2), 224–251. https://doi.org/10.1016/j.mayocp.2014.10.011
Mulhall, J. P., Trost, L. W., Brannigan, R. E., et al. (2018). Evaluation and management of testosterone deficiency: AUA guideline. Journal of Urology, 200(2), 423–432. https://doi.org/10.1016/j.juro.2018.03.115
Sood, A., Hosseinpour, A., Sood, A., et al. (2024). Cardiovascular outcomes of hypogonadal men receiving testosterone replacement therapy: a meta-analysis of randomized controlled trials. Endocrine Practice, 30(1), 2–10. https://doi.org/10.1016/j.eprac.2023.09.012
Wallis, C. J., Lo, K., Lee, Y., et al. (2016). Survival and cardiovascular events in men treated with testosterone replacement therapy: an intention-to-treat observational cohort study. Lancet Diabetes & Endocrinology, 4(6), 498–506. https://doi.org/10.1016/S2213-8587(16)00112-1
Yeap, B. B., Marriott, R. J., Dwivedi, G., et al. (2024). Associations of testosterone and related hormones with all-cause and cardiovascular mortality and incident cardiovascular disease in men: individual participant data meta-analyses. Annals of Internal Medicine, 177(6), 768–781. https://doi.org/10.7326/M23-2781
Medical Disclaimer: This article is for informational purposes only and does not constitute medical advice. Consult a qualified healthcare provider before making any decisions about testosterone replacement therapy or any other treatment.
