Testosterone Replacement Therapy (TRT): Benefits, Risks, and the Evidence

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Categories: Health, Wellness and Ergonomics;
Posted: July 10, 2026
By Howard Farran, DDS, MBA

Testosterone Replacement Therapy (TRT): Benefits, Risks, and the Evidence 

Testosterone replacement therapy has become one of the most emotionally charged topics in men’s health. Conversations that begin with a laboratory value quickly drift into masculinity, aging, discipline, libido, body composition, and personal freedom. One side sees TRT as modern medicine correcting an avoidable decline. The other sees it as a shortcut for men unwilling to accept normal aging.

Both stories are too simple.

The clearest place to begin is diagnosis. The Endocrine Society recommends testosterone treatment only when a man has compatible symptoms and consistently low testosterone confirmed on two separate fasting morning tests. A single low value is not enough. Neither is fatigue, weight gain, poor motivation, erectile dysfunction, or a desire to feel younger.

Those symptoms matter, but they are not specific to testosterone deficiency. Poor sleep, obstructive sleep apnea, obesity, diabetes, alcohol, depression, thyroid disease, medications, chronic stress, and relationship strain can produce the same clinical picture. They can also lower testosterone themselves. A good evaluation therefore asks why the number is low before deciding that the number itself is the disease.

For men with true hypogonadism, TRT can be meaningful. The strongest benefits are improved sexual desire and activity, correction of some cases of anemia, and increased lean body mass. Mood, vitality, walking ability, and bone density may improve, although the effects are usually more modest and less predictable. The lower the pretreatment testosterone and the more specific the symptoms, the more likely the patient is to benefit.

What the evidence does not support is the claim that every older man should be pushed toward 800 or 900 nanograms per deciliter. No major guideline identifies that range as universally optimal. Some men may feel better there, but feeling better is not the same as proving lower rates of heart attack, fracture, disability, dementia, or death.

This distinction matters because the word replacement can hide an important difference. Restoring a clearly deficient hormone is replacement. Raising a normal level toward the upper youthful range for performance, appearance, or vitality is better described as optimization or enhancement. That choice may still be reasonable for an informed patient, but it rests on a thinner evidence base and requires a more honest discussion of uncertainty.

Cardiovascular safety illustrates the problem with broad claims. The TRAVERSE trial enrolled 5,246 men with symptoms, two fasting testosterone levels below 300, and established or high cardiovascular risk. Over about 33 months, major cardiovascular events occurred in 7.0 percent of men receiving testosterone gel and 7.3 percent receiving placebo. Testosterone did not increase the combined rate of cardiovascular death, heart attack, or stroke.

That was reassuring, but narrow. The trial studied men with documented hypogonadism using a regulated gel under close monitoring. It did not establish lifelong safety for pellets, high dose injections, men with normal baseline levels, or poorly supervised anti aging protocols. Atrial fibrillation, acute kidney injury, and pulmonary embolism were also more common in the testosterone group.

The FDA responded in February 2025 by removing the boxed warning about major cardiovascular events. At the same time, it retained the limitation on use for age related low testosterone and added stronger blood pressure warnings across testosterone products. The message was not that TRT is harmless. It was that one broad warning was no longer supported, while a more specific risk remained.

Dentists understand this kind of nuance. A treatment can work and still require careful case selection. A reassuring study can answer one question without answering every question. A better biomarker does not always translate into a better clinical outcome.

Bone health is a good example. Testosterone can increase bone density, yet the fracture analysis from TRAVERSE found more clinical fractures in men receiving testosterone. The reason remains uncertain. Greater activity, trauma, behavioral changes, or biological effects may all contribute. The lesson is familiar. Surrogate measures matter, but patient outcomes matter more.

Fertility is another area where the marketing story often outruns the counseling. External testosterone suppresses LH and FSH, reduces endogenous production, and can sharply lower sperm counts. Men planning future fertility should not begin standard TRT without specialist guidance. Testosterone can also raise hematocrit and blood pressure and may cause acne, edema, breast symptoms, mood changes, and testicular shrinkage. Monitoring is not an optional service. It is part of the treatment.

Pellets deserve the same scrutiny. Their convenience is real, and some patients prefer the steady delivery. Their weakness is reversibility. Once inserted, the dose cannot be adjusted quickly if the level overshoots or adverse effects appear. The word bioidentical offers reassurance, but it does not make the treatment safer. Dose, formulation, achieved level, patient selection, and follow up determine safety.

Obesity further complicates the picture. Excess adiposity can suppress testosterone production, while weight loss can improve endogenous levels. GLP 1 drugs may therefore raise testosterone indirectly by reducing visceral fat and improving metabolic health. That does not make them testosterone drugs. It shows how often the hormone level is part of a larger metabolic story.

For dentists, the practical lesson extends beyond TRT. We see patients every day who want a simple explanation and a fast intervention. They arrive convinced that one implant, one sedative, one antibiotic, or one financing plan will solve a problem created by several interacting causes. Good treatment begins by separating the complaint from the diagnosis, the laboratory value from the outcome, and the testimonial from the evidence.

The best TRT decisions follow the same discipline as sound dentistry. Confirm the diagnosis. Identify reversible causes. Define the outcome that matters. Select the least aggressive effective intervention. Monitor for harm. Stop when the benefit is unclear or the tradeoff changes.

TRT is neither a fountain of youth nor reckless steroid abuse. It is a legitimate treatment for selected men with documented symptomatic deficiency. The further it moves from replacement toward optimization, the more careful the consent, monitoring, and expectations must become.

When does treating decline become good medicine, and when does it become selling youth?

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Testosterone Replacement Therapy (TRT): Benefits, Risks, and the Evidence


Primary clinical guidelines

Endocrine Society. Testosterone Therapy for Hypogonadism Guideline Resources
https://www.endocrine.org/clinical-practice-guidelines/testosterone-therapy

Testosterone Therapy in Men With Hypogonadism. An Endocrine Society Clinical Practice Guideline
https://pubmed.ncbi.nlm.nih.gov/29562364/

FDA. FDA Issues Class-Wide Labeling Changes for Testosterone Products
https://www.fda.gov/drugs/drug-alerts-and-statements/fda-issues-class-wide-labeling-changes-testosterone-products

Testosterone safety and cardiovascular outcomes

Cardiovascular Safety of Testosterone-Replacement Therapy. The TRAVERSE Trial. New England Journal of Medicine
https://pubmed.ncbi.nlm.nih.gov/37326322/

Association Between Long-Term Testosterone Exposure and Major Adverse Cardiovascular Events in Aging Men
https://pmc.ncbi.nlm.nih.gov/articles/PMC12559020/

Testosterone trends and reproductive health

European Society of Human Reproduction and Embryology. Human Reproduction. ESHRE 2026 Annual Meeting Abstract Supplement
https://www.eshre.eu/-/media/sitecore-files/Annual-meeting/ESHRE2026/HUMREP_41_13_without_embargoed.pdf

The Guardian. Men’s Average Testosterone Levels Have Halved in the Last 50 Years, Say Scientists
https://www.theguardian.com/society/2026/jul/07/mens-average-testosterone-levels-have-halved-in-last-50-years-say-scientists

Metabolic health and testosterone

High-Normal Glucose Levels in Nondiabetic and Prediabetic Men Are Associated With Decreased Testosterone Levels
https://pmc.ncbi.nlm.nih.gov/articles/PMC3391640/

Semaglutide and cardiovascular outcomes

Semaglutide and Cardiovascular Outcomes in Obesity Without Diabetes. New England Journal of Medicine
https://www.nejm.org/doi/full/10.1056/NEJMoa2307563

Semaglutide and Cardiovascular Outcomes. Correspondence. New England Journal of Medicine
https://www.nejm.org/doi/full/10.1056/NEJMc2400414

Environmental exposures and microplastics

Bioaccumulation of Microplastics in Decedent Human Brains. Nature Medicine
https://www.nature.com/articles/s41591-024-03453-1

Challenges in Studying Microplastics in Human Brain. Nature Medicine
https://www.nature.com/articles/s41591-025-04045-3

Avoiding and Reducing Microplastic False Positives From Dry Glove Contact. Analytical Methods
https://pubs.rsc.org/ay/article/18/14/2914/1243107/Avoiding-and-reducing-microplastic-false-positives

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