Testosterone therapy is receiving renewed attention, not only from patients but also from regulatory agencies. In recent months, the U.S. Food and Drug Administration (FDA) updated the safety information for testosterone products, reflecting new evidence on cardiovascular risk. This has generated understandable questions among men who are considering therapy and clinicians who prescribe it.

As a urologist, I frequently meet patients who are uncertain about the safety of testosterone treatment, particularly regarding the heart. Much of this concern stems from earlier studies and headlines that suggested a possible increase in cardiovascular events. The updated FDA guidance provides a more nuanced and evidence-based perspective, helping clarify when testosterone therapy is appropriate and how it can be used safely.

Why the FDA revisited testosterone therapy

The FDA first issued cautions about testosterone therapy nearly a decade ago, after several observational studies reported a possible increase in cardiovascular events among men using testosterone. These early data, although limited, raised legitimate concerns and prompted the agency to require stronger safety messaging.

Since then, the landscape has changed. Larger, better-designed randomized trials and long-term follow-up studies have provided more reliable evidence, suggesting that physiologic testosterone replacement, prescribed for men with confirmed hypogonadism, does not appear to increase major adverse cardiac events. At the same time, the use of testosterone has expanded, often without full diagnostic evaluation.

In response to this progressing evidence and changing prescribing environment, the FDA reevaluated the available data to ensure that product labeling accurately reflects current knowledge, supports safe prescribing practices, and helps reduce both misuse and unnecessary fear among patients.

What the FDA’s new guidance actually says

The FDA’s recent update does not declare testosterone therapy universally safe, nor does it reinforce earlier concerns about widespread cardiovascular harm. Instead, it provides a more balanced interpretation of the current evidence.

The revised guidance emphasizes three key points:

1. When used for medically confirmed hypogonadism, testosterone therapy has not been shown to increase major cardiovascular events. This clarification reflects newer clinical trials that did not demonstrate excess risk in appropriately selected patients.
2. Testosterone should be prescribed only to men with clear clinical and biochemical evidence of deficiency. The FDA reinforces that normal aging alone is not an indication for treatment.
3. Ongoing monitoring remains essential. The update highlights the importance of periodic evaluation, including hematocrit, lipids, prostate health, and cardiovascular status, to ensure that therapy remains safe over time.

Rather than broadening access, the FDA’s position aims to guide appropriate use: reducing misuse while reassuring patients who meet clinical criteria that therapy can be considered without undue fear.

What the evidence shows on cardiovascular risk

Cardiovascular safety has been one of the central questions surrounding testosterone therapy for more than a decade. Early retrospective studies suggested a possible association between testosterone use and heart attacks or stroke, but these findings were limited by methodological weaknesses, including confounding factors, inconsistent dosing, and incomplete patient characterization.

More recent evidence provides a clearer picture. Large randomized controlled trials and long-term observational studies have shown that physiologic testosterone replacement, aimed at restoring normal levels, does not increase major adverse cardiovascular events in men with confirmed hypogonadism. In properly designed trials, event rates were similar between men receiving testosterone and those receiving placebo.

Importantly, these studies distinguish medically supervised therapy from non-medical or supraphysiologic use. Cardiovascular concerns are more relevant in scenarios involving unregulated products, excessive dosing, or use in individuals with unstable heart disease, situations that fall outside the scope of evidence-based treatment.

The current scientific consensus supports a more nuanced view: Testosterone therapy carries risks, but when prescribed correctly and monitored appropriately, cardiovascular harm has not been demonstrated in the populations for whom treatment is intended.

Patients who should still be cautious

Although updated evidence is reassuring for many men, testosterone therapy is not appropriate for everyone. Certain clinical situations warrant caution, closer monitoring, or temporary postponement of treatment.

1. Men with unstable cardiovascular disease. Individuals with recent myocardial infarction, stroke, or decompensated heart failure remain at higher risk, and initiating testosterone in this setting is generally avoided until their condition stabilizes.

2. Men with uncontrolled cardiovascular risk factors. Poorly managed hypertension, significant dyslipidemia, or untreated obstructive sleep apnea can amplify potential risks and should be addressed before considering therapy.

3. Men without confirmed hypogonadism. Using testosterone without documented low levels exposes patients to potential side effects, including possible cardiovascular strain, without any medical benefit.

4. Men using non-prescription or supraphysiologic doses. Products obtained outside the medical system, as well as doses aimed at achieving levels above the physiologic range, fall outside the FDA’s guidance and carry substantially greater risk.

These cautions underscore the principle that testosterone therapy should be individualized, evidence-based, and supported by thorough diagnostic evaluation and follow-up.

What this means for men considering testosterone therapy

For men experiencing symptoms of low testosterone, the updated FDA guidance offers a more evidence-based framework for decision-making. It underscores that testosterone therapy can be considered safe when it is used for the right indications and monitored appropriately.

A thorough diagnostic evaluation remains essential. This includes confirming low serum testosterone levels on at least two separate morning measurements, assessing related symptoms, and evaluating potential causes such as pituitary or systemic conditions. Laboratory testing may also include LH, FSH, SHBG, hematocrit, lipids, and, when appropriate, PSA.

Monitoring is a central part of safe therapy. Regular follow-up allows clinicians to adjust dosage, track hematocrit and lipid levels, evaluate cardiovascular status, and ensure prostate health. This ongoing attention is a key factor in maintaining safety and effectiveness.

Testosterone therapy aims to restore normal physiology, not exceed it. Patients sometimes expect dramatic changes, but the goal is to bring testosterone into the normal range to improve symptoms, energy, libido, mood, and metabolic parameters in a controlled and medically supported way.

For men who meet diagnostic criteria, this updated guidance provides reassurance that treatment can be both effective and safe when managed in a structured clinical environment.

Evidence evolves and so should public understanding

The FDA’s updated guidance reflects an important principle in medicine: As stronger evidence becomes available, clinical recommendations must adapt. Early concerns about testosterone therapy were based on limited and inconsistent data, but newer, more rigorous studies have reshaped our understanding of cardiovascular risk.

Public perception, however, often lags behind scientific progress. Many men continue to view testosterone therapy as inherently dangerous, while others pursue it without adequate evaluation or supervision. Both extremes highlight the need for clearer communication and shared decision-making.

Endocrinologists, urologists, and other clinicians all play a central role in bridging this gap. By grounding treatment discussions in current evidence and emphasizing appropriate use and monitoring, we can help patients make informed choices rather than decisions driven by fear or misinformation.

Conclusion

The FDA’s updated guidance provides a clearer and more evidence-based understanding of testosterone therapy and cardiovascular risk. For men with confirmed hypogonadism, current data do not show an increased rate of major cardiac events when therapy is prescribed and monitored appropriately. What remains essential is a structured diagnostic approach, careful assessment of cardiovascular and prostate health, and ongoing follow-up to ensure that treatment stays within the physiologic range. Misuse, whether through supraphysiologic dosing, non-prescription products, or inadequate monitoring, continues to carry real risk and falls outside the scope of the FDA’s reassurance. By working collaboratively, urologists, endocrinologists, and primary care clinicians can guide patients through this evolving landscape, helping them make informed decisions grounded in evidence rather than outdated concerns or misinformation.

Martina Ambardjieva is a dedicated urologist and medical educator with extensive experience in both clinical practice and academic instruction. She earned her MD from the University “Sv. Kiril i Metódij” in Skopje and is a PhD candidate in urological oncology, with a focus on bladder carcinoma. Her scholarly work includes numerous publications in oncologic urology, urinary calculosis, and men’s health.

Dr. Ambardjieva currently serves as a urologist at the PHI University Surgical Clinic “Naum Ohridski” and completed her residency training at the University Urology Clinic in Skopje. Earlier in her career, she practiced as a general medical doctor at Sante Plus General Hospital and completed a medical internship at the University of Ljubljana.

In addition to her clinical responsibilities, Dr. Ambardjieva is a teaching assistant at the Medical Faculty in Skopje. She works additionally as a collaborator for Dr. Telx. She has held leadership positions in the European Medical Students’ Association and actively participates in international medical education and policy. She has attended numerous congresses and workshops in France, Italy, Canada, and Turkey, and serves as a delegate for the European Association of Urology (EAU), contributing to cross-border initiatives in urology. Certified in laparoscopic surgery, she continues to integrate patient care, research, and education in her professional work.