Testosterone replacement therapy can improve sex drive, erections, mood and bone density in men whose testosterone is truly low, and it did not raise heart attack or stroke risk in the largest safety trial so far. It also thickens the blood, raises blood pressure a little, shuts down sperm production and, in one 2024 analysis, came with more fractures than placebo. Which delivery method you use changes several of those risks.
Quick answer: In men with confirmed low testosterone, TRT has good evidence for better sexual desire and erectile function, slightly better mood and higher bone density. It did not improve energy in the Testosterone Trials. The main risks are a rising red blood cell count, higher blood pressure, lower fertility and, in the TRAVERSE trial, more atrial fibrillation and fractures. Injections, gels, oral capsules, nasal gel and pellets each trade convenience against a different risk.
What testosterone replacement therapy is
TRT gives the body testosterone from outside when the testes, or the brain signals that drive them, no longer make enough. It is meant for hypogonadism: symptoms plus low levels on repeat testing. The American Urological Association guideline uses a total testosterone below 300 ng/dL on two separate early-morning tests as a reasonable cut-off.
That definition matters for everything below. The benefits in the trials were measured in men who met it, not in men with normal levels chasing more energy.
Benefits of testosterone replacement therapy
The best data come from two large placebo-controlled studies.
The Testosterone Trials, published in the New England Journal of Medicine in 2016, gave testosterone gel or placebo gel for one year to 790 men aged 65 and older with testosterone under 275 ng/dL. Men on testosterone had more sexual activity, more sexual desire and better erectile function. Their mood was slightly better and depressive symptoms slightly lower. Walking distance improved in more of them (20.5 percent vs 12.6 percent). Energy, which the study called vitality, did not improve.
That last result surprises people. Fatigue is the symptom that sends most men to get tested, and it is the one TRT was least able to fix in older men.
Bone is the other clear gain. Testosterone raises bone mineral density in hypogonadal men. Whether that turns into fewer broken bones is a different question, covered in the risks below.
What TRT does not reliably do is turn a tired man with normal testosterone into an energetic one. If your levels are normal, the fatigue has another cause, and our post on low testosterone and erectile dysfunction explains why sexual symptoms in particular often have more than one driver.
Risks of TRT, including what TRAVERSE found
Heart attack and stroke
For about a decade the worry was the heart. The TRAVERSE trial tested it directly. It randomized 5,204 men aged 45 to 80 with low testosterone and existing heart disease or high cardiac risk to testosterone gel or placebo, and followed them for about 33 months on average. Major cardiac events (heart attack, stroke or cardiovascular death) happened in 7.0 percent of the testosterone group and 7.3 percent of the placebo group.
On February 28, 2025, the FDA ordered class-wide labeling changes: TRAVERSE results were added to every testosterone product, and the boxed-warning language about increased cardiovascular risk was removed.
Heart rhythm, kidneys and clots
TRAVERSE was not a clean bill of health. The testosterone group had more atrial fibrillation, more acute kidney injury (2.3 percent vs 1.5 percent), more pulmonary embolism and more nonfatal arrhythmias needing treatment (5.2 percent vs 3.3 percent).
Blood pressure
The same 2025 FDA action added blood pressure warnings across all testosterone products, because ambulatory monitoring studies showed the whole class raises it. The effect is usually a few points. In the review of oral testosterone below, Jatenzo raised systolic pressure by 3 to 6 mm Hg on average, and 7.2 percent of men started blood pressure medicine.
Thicker blood
Testosterone stimulates red blood cell production. Guidelines generally use a hematocrit of 54 percent as the point to stop, lower the dose or not start. A 2024 review in Endocrine Connections found every formulation raises hematocrit, with intramuscular cypionate and enanthate injections the most potent. In TRAVERSE, which used gel, under 1 percent of men went above 54 percent after dose adjustment. In the T4DM trial, which used long-acting undecanoate injections, 22 percent did.
That gap is the strongest argument for choosing the delivery method on purpose rather than by habit.
Fractures
A TRAVERSE fracture analysis in the New England Journal of Medicine in 2024 found clinical fractures in 3.50 percent of men on testosterone and 2.46 percent on placebo. Bone density goes up on TRT, yet fractures did not go down in this trial. Nobody has a settled explanation. More activity, and more falls, is one guess.
Fertility
Testosterone from outside tells the brain to stop sending LH and FSH, and sperm production drops, sometimes to zero. The AUA guideline says men who are trying to conceive should not be put on testosterone. We cover the details in does testosterone replacement therapy cause infertility.
Prostate and hair
PSA is checked before and during treatment. Our post on PSA, testosterone and prostate cancer explains what the numbers mean. Some men also notice hair thinning, which we cover in can testosterone replacement therapy cause hair loss.
TRT delivery methods compared
| Method | How often | Main trade-off |
|---|---|---|
| Cypionate or enanthate injection | Weekly to every 2 weeks | Cheap and effective; biggest rise in hematocrit; peaks and troughs |
| Subcutaneous autoinjector (Xyosted) | Weekly | Small needle under the skin; carries a boxed blood pressure warning |
| Long-acting undecanoate injection (Aveed) | About every 10 weeks, in clinic | Few visits; rare oil microembolism and allergic reactions mean a restricted program and 30 minutes of observation |
| Gel or cream | Daily | Steady levels; can transfer to partners and children through skin contact |
| Oral capsules (Jatenzo, Tlando, Kyzatrex) | Twice daily with food | No needles or transfer; blood pressure rises, boxed warning on two brands |
| Nasal gel (Natesto) | Three times daily | Short-acting; small studies suggest it suppresses your own production less; easy to miss doses |
| Pellets under the skin | Every 3 to 6 months | Hands-off; a minor procedure each time, pellets can work their way out, and a dose cannot be pulled back once placed |
Gels have carried a boxed warning about secondary exposure since 2009, after children developed early puberty from touching a parent’s skin. If you have young kids at home, that alone often settles the choice. Creams work the same way, and we compare them in the advantages of transdermal cream for TRT.
The three oral capsules are all testosterone undecanoate taken twice a day with a meal. A comparative review of Jatenzo, Tlando and Kyzatrex notes Jatenzo and Kyzatrex carry boxed warnings for blood pressure.
Our view: pick the method you will actually use correctly for years, then check hematocrit and blood pressure more often if you pick injections. The cheapest option is not the right one for a man whose hematocrit already sits near the top of normal.
Monitoring once you start
The Endocrine Society and AUA both call for follow-up labs after starting and then regularly once stable. The usual checks are total testosterone, hematocrit, PSA in men over 40 and blood pressure, with the dose or method changed if hematocrit climbs toward 54 percent. Most TRAVERSE participants were on treatment for under three years, so long-term data in younger men are still thin, and that is worth weighing if you are 35 and thinking about decades of treatment.
Frequently asked questions
What are the main benefits of testosterone replacement therapy?
In men with confirmed low testosterone, the Testosterone Trials found better sexual desire, sexual activity and erectile function, slightly better mood and a modest improvement in walking. Testosterone also raises bone density. The same trials found no improvement in energy or vitality, so fatigue alone is a weak reason to start.
Is testosterone replacement therapy bad for your heart?
The TRAVERSE trial of 5,204 men found major cardiac events in 7.0 percent on testosterone and 7.3 percent on placebo, and in 2025 the FDA removed cardiovascular risk language from the boxed warning. The trial did find more atrial fibrillation, pulmonary embolism and acute kidney injury, and all testosterone products now carry blood pressure warnings.
What is the safest way to take testosterone?
No method is safest for everyone. Gels raise hematocrit less than intramuscular injections but can transfer to children. Injections are effective and inexpensive but raise hematocrit the most. Oral capsules avoid needles and transfer but raise blood pressure. The right choice depends on your labs, your household and which routine you will keep.
Does TRT affect fertility?
Yes. Testosterone from outside suppresses the LH and FSH signals that drive sperm production, and sperm counts can fall to zero. The American Urological Association advises against testosterone therapy for men who are currently trying to conceive. Men who want children soon should discuss other options before starting.
How often do you need blood work on TRT?
Guidelines call for labs a few months after starting and then at regular intervals once stable. Checks usually include testosterone, hematocrit, PSA for men over 40 and blood pressure. A hematocrit approaching 54 percent is the common signal to lower the dose, change the method or pause treatment.
If you are weighing these trade-offs with your own labs, Dr. Drew Collins, ND, reviews repeat morning testosterone results, hematocrit and PSA before recommending any method, and explains how testosterone replacement therapy at our Bend clinic is monitored after you start.
Sources
- Snyder PJ, et al. Effects of Testosterone Treatment in Older Men. New England Journal of Medicine, 2016 (American College of Cardiology summary).
- Lincoff AM, et al. Cardiovascular Safety of Testosterone-Replacement Therapy (TRAVERSE). New England Journal of Medicine, 2023 (HCPLive summary).
- Snyder PJ, et al. Testosterone Treatment and Fractures in Men with Hypogonadism. New England Journal of Medicine, 2024 (Cleveland Clinic summary).
- U.S. Food and Drug Administration. FDA issues class-wide labeling changes for testosterone products, February 28, 2025.
- Bond P, Verdegaal T, Smit DL. Testosterone therapy-induced erythrocytosis: can phlebotomy be justified? Endocrine Connections, 2024.
- Treatment of Symptomatic Male Hypogonadism with New Oral Testosterone Therapies: A Comparative Review of Jatenzo, Tlando, and Kyzatrex.
- American Urological Association. Evaluation and Management of Testosterone Deficiency guideline.
This article is for education and is not a diagnosis. Talk with a licensed clinician about your own labs and symptoms.
Want to talk this through for your own health? Book a visit with Dr. Drew Collins, ND at 601 NW Harmon Blvd in Bend, or call (858) 333-5196.
