TRT's main known risks are increased blood pressure, higher red blood cell counts (which can raise clot risk), reduced sperm production and fertility, worsening sleep apnea, acne and prostate effects. Large trials published since 2023 found no increase in heart attacks or strokes in men with diagnosed low testosterone, but did find higher rates of pulmonary embolism and fractures. TRT is a prescription treatment for diagnosed low testosterone, not for normal aging, and it needs ongoing monitoring.
This page summarizes guidance from the FDA, the Endocrine Society, Mayo Clinic and peer-reviewed research as of September 2026. It's general information, not medical advice. Talk to a licensed clinician about your own risks.
Who TRT is for (and who it isn't)
The FDA approves testosterone products for men with clinically diagnosed low testosterone, and it keeps a "limitation of use" stating that safety and efficacy haven't been established for age-related low testosterone (FDA). Mayo Clinic says "treating normal aging with testosterone therapy is not advisable," and notes little evidence that testosterone improves vitality or energy in otherwise healthy men (Mayo Clinic).
The Endocrine Society's July 2026 statement stresses that diagnosis requires symptoms plus consistently low testosterone on at least two early-morning, fasting tests, and warns that vague terms like "age-related hypogonadism" "blur the line between treatable disease and normal aging" (Endocrine Society).
Known side effects and risks
Blood pressure
In February 2025, the FDA required class-wide labeling changes for all testosterone products, adding a new warning about increased blood pressure after ambulatory blood pressure studies confirmed increases across products (FDA). Some oral testosterone products carry product-specific warnings; for example, Kyzatrex's label says blood pressure increases can raise the risk of major adverse cardiovascular events and requires monitoring (Kyzatrex information).
Red blood cells and blood clots
Testosterone can stimulate excess red blood cell production (raised hematocrit), which Mayo Clinic notes can increase the risk of blood clots (Mayo Clinic). The Endocrine Society recommends against starting TRT in men with elevated hematocrit and calls for monitoring during treatment (guideline). The Endocrine Society's 2026 statement reports that the TRAVERSE trials found roughly a 50% relative increase in pulmonary embolism among treated men (Endocrine Society).
Fertility and testicular size
Testosterone therapy can reduce sperm production and cause testicular shrinkage (Mayo Clinic). The Endocrine Society recommends against TRT for men planning fertility in the near term (guideline). Some clinics offer medications like enclomiphene or clomiphene that work differently; whether they're appropriate is a clinical decision. Enclomiphene isn't FDA-approved on its own (OPSS).
Sleep apnea
TRT can worsen sleep apnea (Mayo Clinic), and the Endocrine Society recommends against it in men with untreated severe obstructive sleep apnea.
Prostate
Testosterone can stimulate prostate growth, both benign and cancerous (Mayo Clinic). The guideline recommends against TRT in men with prostate cancer, a palpable prostate nodule, or PSA above 4 ng/mL (or above 3 ng/mL in higher-risk men) without further urological evaluation, and recommends a urology consultation if PSA rises by more than 1.4 ng/mL in the first 12 months (guideline). The Endocrine Society notes long-term prostate cancer risk remains uncertain because trials "may not have followed men long enough."
Fractures
The TRAVERSE program also found elevated fracture rates among treated men, according to the Endocrine Society's 2026 statement (Endocrine Society).
Skin and breast
Acne, other skin reactions and breast enlargement are listed side effects (Mayo Clinic).
What about the heart?
For years, the FDA's boxed warning flagged a possible increase in cardiovascular risk. The TRAVERSE trial, a randomized trial that enrolled 5,246 men aged 45 to 80 with low testosterone and existing or high risk of cardiovascular disease, found testosterone was noninferior to placebo for major adverse cardiac events (NEJM, Lincoff et al., 2023; HCPLive summary). Based on this, the FDA in 2025 removed the boxed-warning language about increased risk of adverse cardiovascular outcomes, while adding the blood-pressure warning (FDA).
That's reassuring, but it applies to men with properly diagnosed low testosterone who were monitored in a trial. It doesn't make testosterone risk-free, and the same trial program produced the pulmonary embolism and fracture signals above. The Endocrine Society has called for a long-term "Men's Health Initiative" to close the remaining evidence gaps.
Who shouldn't start TRT
The Endocrine Society guideline recommends against TRT in men with (guideline):
- Plans for fertility in the near term
- Breast or prostate cancer
- A palpable prostate nodule, or elevated PSA without urological evaluation
- Elevated hematocrit
- Untreated severe obstructive sleep apnea
- Severe lower urinary tract symptoms
- Uncontrolled heart failure
- Heart attack or stroke within the last 6 months
- Thrombophilia (a tendency to form blood clots)
How monitoring reduces risk
Most of these risks can be tracked. Expect a legitimate clinic to check hematocrit, PSA (where appropriate), estradiol and blood pressure at baseline and during treatment. When comparing clinics, look at whether follow-up labs are included; see TRT clinic cost in 2026 and how online TRT works.
Compounded vs FDA-approved medication
Many online clinics dispense compounded testosterone or enclomiphene. The FDA states that "compounded drugs are not FDA-approved," meaning the agency doesn't verify their safety, effectiveness or quality before they're sold (FDA). Ask your clinic which you're getting.
The bottom line
TRT can be an appropriate treatment for men with confirmed low testosterone, but it's a long-term prescription with real risks that require monitoring. Don't start, stop or change testosterone without a licensed clinician. If you're comparing providers, our best online TRT clinics ranking weighs medical oversight at 30% of each score, and our Hone Health and Fountain TRT reviews detail each clinic's lab and follow-up policies.