Testosterone prescriptions for men rose sharply over the past two decades, driven partly by direct-to-consumer marketing rather than by new evidence. Then in 2023 the largest safety trial ever conducted reported its results. Here is what is now established, what remains uncertain, and where the marketing has run ahead of the science.
Key facts
- Treatment is indicated for diagnosed hypogonadism: consistent symptoms plus unequivocally low morning testosterone confirmed on at least two separate occasions.1
- The TRAVERSE trial (5,246 men, 2023) found testosterone therapy non-inferior to placebo for major cardiovascular events in men with hypogonadism and existing cardiovascular risk.2
- The Testosterone Trials found a moderate benefit for sexual function, a smaller effect on mood and walking distance, and no benefit for vitality.3
- Testosterone therapy suppresses sperm production and can cause infertility, sometimes persistently.1
- Testosterone is not recommended as a treatment for age-related decline alone in men without diagnosed hypogonadism.1
What hypogonadism actually is
Male hypogonadism is a clinical syndrome: consistent symptoms and signs together with unequivocally low serum testosterone. Both halves are required. A low number without symptoms is not the diagnosis, and symptoms without a low number are not either.1
The Endocrine Society clinical practice guideline recommends diagnosing only after measuring fasting morning total testosterone on at least two separate mornings using a reliable assay.1 This matters more than it sounds. Testosterone follows a daily rhythm, peaking in the morning, and varies substantially day to day. A single afternoon draw is a common way to be told you are deficient when you are not.
Acute illness, sleep deprivation, significant weight gain, opioid use, and certain medications all suppress testosterone temporarily. Guidelines advise correcting reversible causes before committing someone to lifelong therapy.1
Total, free, and SHBG
Most testosterone in blood is bound to sex hormone-binding globulin (SHBG) and albumin; only a small fraction circulates free. When SHBG is abnormal, which happens with obesity, diabetes, thyroid disease, and aging, total testosterone can misrepresent the biologically available amount. Guidelines recommend measuring free testosterone in those situations, using an accurate method.14
What the evidence shows about benefits
The Testosterone Trials were a coordinated set of placebo-controlled randomized trials in men over 65 with unequivocally low testosterone.3 The results were mixed, and that nuance is usually lost in summary:
| Outcome | Finding |
|---|---|
| Sexual function | Consistent, moderate improvement in activity, desire, and erectile function5 |
| Mood and depressive symptoms | Small but statistically significant improvement |
| Walking distance | Modest improvement, not significant in the primary analysis |
| Vitality and energy | No significant benefit |
That last row deserves emphasis, because “low energy” is the single most common reason men seek testosterone. In the trial designed to test exactly that, testosterone did not significantly improve vitality.3
Cardiovascular safety, and what changed in 2023
For a decade the central open question was whether testosterone therapy increased heart attacks and strokes. Observational studies conflicted, and in 2015 the FDA required a cardiovascular safety warning on testosterone labels.
TRAVERSE was designed to settle it. It randomized 5,246 men aged 45 to 80 with hypogonadism and either existing cardiovascular disease or high risk of it, to testosterone gel or placebo, and followed them for a mean of about 33 months.2
The result: testosterone was non-inferior to placebo for the primary endpoint of major adverse cardiac events, meaning cardiovascular death, non-fatal heart attack, or non-fatal stroke.2
Two cautions on how that gets reported. Non-inferiority means the trial ruled out a meaningful increase in risk; it does not show testosterone protects the heart. And the trial did find higher rates of some secondary events in the testosterone group, including atrial fibrillation, acute kidney injury, and pulmonary embolism.2 “Cardiovascular safety established” is a fair headline. “Testosterone is good for your heart” is not.
Risks and things people are not told
Fertility
This is the most consequential under-disclosed risk. Exogenous testosterone suppresses the signals that drive sperm production, and can reduce sperm counts to zero. Recovery after stopping is usual but can take many months and is not guaranteed.1 Guidelines advise against testosterone therapy in men who want children in the near term. If nobody raised fertility with you before prescribing, that is a significant gap.
Erythrocytosis
Testosterone raises red blood cell production. Excessive rises thicken the blood and increase clot risk, which is why hematocrit must be monitored before treatment, at three to six months, and annually thereafter.1 It is the most common reason therapy is paused or dose-reduced.
Prostate
Testosterone does not appear to cause prostate cancer, but it can accelerate an existing one. Guidelines recommend prostate risk assessment before starting in men over 40 with a baseline PSA, and follow-up monitoring.1
Other effects
Acne, oily skin, breast tenderness or enlargement, testicular shrinkage, fluid retention, and worsening of untreated obstructive sleep apnea.1
Who should not take it
Guidelines advise against starting testosterone in men with untreated prostate or breast cancer, an unevaluated prostate nodule or elevated PSA, hematocrit above the threshold, untreated severe obstructive sleep apnea, uncontrolled heart failure, a recent cardiovascular event, or a desire for fertility in the near term.1
Monitoring, if you do start
- Testosterone level at three to six months, then annually, aiming for the mid-normal range.
- Hematocrit at baseline, three to six months, then annually.
- Prostate assessment per guideline in men over 40.
- Symptom reassessment: if there is no meaningful benefit after a reasonable trial, the honest step is stopping rather than escalating the dose.
Frequently asked questions
Does testosterone therapy cause heart attacks?
The TRAVERSE trial, the largest randomized safety study to date, found testosterone non-inferior to placebo for major adverse cardiac events in men with hypogonadism and elevated cardiovascular risk. It did observe higher rates of atrial fibrillation, pulmonary embolism, and acute kidney injury in the testosterone group.
Will it give me more energy?
In the trial specifically designed to test vitality in older men with low testosterone, there was no significant benefit. Sexual function improved consistently; energy did not.
Is testosterone therapy permanent?
For most men with true hypogonadism it is ongoing, because stopping returns levels to baseline. Therapy also suppresses natural production while it is being taken, so stopping after long use can involve a period of low levels before recovery.
I feel bad but my level is normal. Should I still try it?
Guidelines recommend against testosterone in men without diagnosed hypogonadism. Symptoms like fatigue, low libido, and poor concentration are non-specific and commonly caused by sleep disorders, depression, thyroid disease, anemia, or medication effects, all worth investigating.
The bottom line
For men with properly diagnosed hypogonadism, testosterone therapy has a reasonable evidence base for sexual function, and its cardiovascular safety is now better established than it was. For men with borderline numbers, non-specific symptoms, and no confirmed diagnosis, the evidence does not support it, and the risks around fertility, red cell mass, and prostate monitoring are real.
The distinction between those two groups is the whole question, and it is exactly the distinction a marketing-driven clinic has an incentive to blur.