Testosterone Therapy Without Confirmed Deficiency

Can Testosterone Therapy Increase Cardiovascular Risk?

The TRAVERSE trial, published in The New England Journal of Medicine in 2023, enrolled 5,246 men with symptoms of hypogonadism, repeatedly measured low testosterone and existing cardiovascular disease or elevated cardiovascular risk. Testosterone gel was noninferior to placebo for the trial's composite of major adverse cardiovascular events, but pulmonary embolism, atrial fibrillation and acute kidney injury occurred more often in the testosterone group. These findings provide reassurance about the primary cardiovascular outcome in the population studied, not proof that testosterone is harmless for anyone seeking greater strength, energy or sexual performance.

People without documented deficiency have a different benefit-risk balance because meaningful clinical benefit has not been established. Testosterone can raise hematocrit, promote fluid retention and increase blood pressure in some patients, creating plausible pathways for harm. The US Food and Drug Administration has required testosterone labeling to reflect blood-pressure findings and continues to limit approved use to men with low testosterone associated with specified medical conditions.

Who Should Be Diagnosed With Testosterone Deficiency?

The Endocrine Society recommends diagnosing hypogonadism only when symptoms or signs are accompanied by consistently low serum testosterone. Because levels vary with time of day, illness, sleep, nutrition and laboratory methods, an initially low result should ordinarily be confirmed with another morning fasting measurement. Further evaluation may include free testosterone when total testosterone is difficult to interpret and tests that help distinguish testicular disease from pituitary or hypothalamic causes.

Fatigue, reduced libido, erectile difficulties and loss of muscle mass are not specific to testosterone deficiency. Sleep apnea, depression, medication effects, obesity, diabetes, thyroid disease and cardiovascular illness can produce similar symptoms. Prescribing testosterone before investigating these possibilities may delay the correct diagnosis while exposing the patient to treatment risks.

How Can Testosterone Be Used More Safely?

Before treatment, clinicians should discuss fertility plans because external testosterone can suppress sperm production. Guidelines also advise evaluating factors such as elevated hematocrit, prostate health, untreated severe obstructive sleep apnea, recent major cardiovascular events and thrombosis risk. Testosterone should not be started solely to counter normal aging or improve athletic performance.

Follow-up commonly includes assessment of symptoms, testosterone concentration, hematocrit and treatment-specific adverse effects; blood-pressure monitoring is also important. Treatment should be reconsidered when levels normalize but the intended symptoms do not improve. Chest pain, sudden shortness of breath, one-sided leg swelling or signs of stroke require urgent medical assessment rather than adjustment of testosterone without professional guidance.