Originally written by ZRT Laboratory author. Reproduced with permission. Last reviewed: May 2026.
Testosterone therapy in men has attracted significant media attention in recent years, with headlines frequently warning of increased heart attack risk. But a closer look at the underlying research reveals a far more nuanced picture — one where age, pre-existing cardiovascular disease, oestrogen levels, dosage, and delivery method all play important roles.
This article examines the key findings from a landmark study on testosterone therapy and cardiovascular outcomes, explores the clinical questions it raises, and outlines what men and their healthcare providers should consider before starting or continuing testosterone therapy.
What Did the Research Find?
A widely cited study analysed insurance data from 55,593 men who initiated testosterone therapy. Participants were divided into groups based on age and pre-existing cardiovascular disease status, and outcomes were compared against men using phosphodiesterase type 5 inhibitors (PDE5Is) such as sildenafil (Viagra) or tadalafil — medications used to facilitate erections without directly affecting testosterone or libido.
Key Findings by Group
- Men over 65 with known heart disease had approximately twice the risk of myocardial infarction (MI) after starting testosterone therapy.
- Men over 65 without known cardiovascular disease also showed approximately twice the risk of MI, despite having no prior diagnosis — suggesting that age itself is a significant cardiovascular risk factor independent of clinical history.
- Men under 65 with cardiovascular disease showed a two- to three-fold increased risk of MI.
- Men under 65 without known cardiovascular disease showed no increased risk of MI — a critically important finding, as this is the fastest-growing group of men initiating testosterone therapy.
- Men using PDE5I medications showed no increase in MI rates, regardless of age or cardiovascular status.
What Does This Research Tell Us?
Several important conclusions can be drawn from these findings.
Age May Be a Better Cardiovascular Predictor Than Diagnosis
The fact that men over 65 without a prior cardiovascular diagnosis still showed elevated MI risk suggests that age-related cardiovascular changes — including subclinical atherosclerosis, arterial stiffness, and reduced cardiac reserve — may not always be captured by existing diagnoses. A clean medical history does not necessarily mean a clean cardiovascular system in older men.
Sexual Activity Alone Is Not the Trigger
Because men using PDE5I medications — which facilitate erections but do not enhance libido or drive increased physical activity — showed no increase in MI rates, sexual activity alone is unlikely to explain the elevated risk seen in testosterone users. Testosterone appears to drive broader behavioural changes, including increased physical exertion and activity levels, which may place greater demands on a compromised cardiovascular system.
Younger Men Without Cardiovascular Disease Appear to Be at Low Risk
The absence of increased MI risk in men under 65 without cardiovascular disease is reassuring and clinically significant. This group is more likely to exercise regularly, less likely to aromatise testosterone excessively into oestrogen, and more likely to have sufficient cardiac reserve to tolerate the physiological changes associated with testosterone therapy.
Key Clinical Questions the Research Raises
While the study provides important data, it also highlights several unanswered questions that have significant implications for clinical practice.
What Is the Role of Oestrogen?
Testosterone is converted to oestradiol (oestrogen) in the body via the enzyme aromatase. In men who aromatise heavily — particularly those who are older, carry excess body fat, or use higher doses — testosterone therapy can lead to elevated oestrogen levels. High oestrogen in men is associated with increased clotting risk, fluid retention, and cardiovascular strain. The study did not examine oestrogen levels or aromatase activity, leaving this as a potentially important confounding variable.
Does Delivery Method Matter?
The study did not differentiate between delivery methods — topical gels, injections, pellets, or sublingual preparations. Each method produces a different pharmacokinetic profile, with injections creating supraphysiological peaks followed by troughs, while topical preparations tend to produce more stable levels. Whether delivery method influences cardiovascular outcomes remains an important open question.
Does Dosage Make a Difference?
The study also did not stratify results by dose. Clinical experience suggests that men using topical testosterone at doses of 100 mg or more may show elevated oestrogen, suppressed LH, and raised red blood cell counts — markers of cardiovascular concern — even when serum testosterone values appear low. This suggests that serum testosterone alone may underestimate actual tissue assimilation, and that monitoring a broader panel of markers is essential.
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What Happens Beyond the First 90 Days?
The study focused on the period immediately following initiation of testosterone therapy. Whether cardiovascular risk normalises, persists, or changes over longer periods of treatment remains unknown from this data alone.
Clinical Perspective: What Should Men and Their Doctors Consider?
Based on the available evidence, several practical principles emerge for men considering or currently using testosterone therapy.
Exercise Caution in Men Over 65
The elevated MI risk in older men — with or without a prior cardiovascular diagnosis — warrants careful patient selection and thorough cardiovascular assessment before initiating therapy. Men in this age group who do begin testosterone therapy should be counselled to ease gradually into increased physical activity rather than rapidly returning to the exertion levels of their younger years.
Monitor Oestrogen, Red Blood Cell Indices, and Cardiovascular Markers
Monitoring testosterone in isolation is insufficient. Oestradiol, haematocrit, haemoglobin, red blood cell count, and cardiovascular risk markers should all be assessed regularly during therapy. Elevated oestrogen and raised red blood cell indices are early warning signs of cardiovascular strain that can be addressed through dose adjustment, delivery method change, or the addition of an aromatase inhibitor.
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Use Physiological Doses
Dosing testosterone to achieve supraphysiological levels increases the risk of aromatisation, erythrocytosis, and cardiovascular strain. Physiological dosing — aiming to restore levels to the mid-normal range for age — is associated with a more favourable risk profile.
Reassurance for Younger Men Without Cardiovascular Disease
The data provides meaningful reassurance for men under 65 without known cardiovascular disease. This group showed no increased MI risk, and the physiological benefits of restoring testosterone to optimal levels — including improved body composition, energy, mood, libido, and metabolic health — are well established.
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Frequently Asked Questions
Does testosterone therapy cause heart attacks?
The research suggests that testosterone therapy may increase MI risk in men over 65 and in men of any age with pre-existing cardiovascular disease, particularly in the first 90 days of treatment. Men under 65 without known cardiovascular disease did not show an increased risk in the same study. The relationship is complex and likely influenced by oestrogen levels, dosage, delivery method, and individual cardiovascular health.
Is testosterone therapy safe for men under 65?
Based on current evidence, men under 65 without known cardiovascular disease appear to be at low risk of MI from testosterone therapy. However, safe use still requires appropriate baseline assessment, physiological dosing, and regular monitoring of oestrogen, red blood cell indices, and cardiovascular markers.
Why does oestrogen matter in men on testosterone therapy?
Testosterone is converted to oestradiol (oestrogen) by the enzyme aromatase. In men who aromatise heavily, testosterone therapy can lead to elevated oestrogen levels, which are associated with increased clotting risk, fluid retention, and cardiovascular strain. Monitoring oestradiol alongside testosterone is essential for safe therapy management.
What should be monitored during testosterone therapy?
Key markers to monitor include total and free testosterone, oestradiol, SHBG, LH, haematocrit, haemoglobin, red blood cell count, blood pressure, lipids, and PSA. Monitoring frequency should be at least every three to six months during the first year of therapy, and annually thereafter if levels are stable.
Does the delivery method of testosterone affect cardiovascular risk?
Delivery method likely influences cardiovascular risk, though the evidence is not yet definitive. Injections create peak-and-trough hormone fluctuations that may increase aromatisation and erythrocytosis risk. Topical preparations tend to produce more stable levels but can still lead to elevated oestrogen and red blood cell indices at higher doses. The optimal delivery method depends on individual patient factors and should be determined in consultation with a knowledgeable clinician.
Originally written by ZRT Laboratory author. Reproduced with permission. Last reviewed: May 2026.