Introduction

The relationship between testosterone and cardiovascular health has never been a simple one. For decades, the hormone was portrayed as a biological antagonist to cardiac wellbeing—an agent that fuels aggression, risk-taking, and, allegedly, coronary disease. Yet contemporary research paints a far more nuanced and scientifically compelling portrait. Testosterone is not merely a reproductive hormone; it is a systemic regulator acting on metabolic pathways, vascular tone, myocardial tissue, inflammatory processes, and autonomic function.

The review “Testosterone and the Heart” presents an evidence-based, clinically grounded perspective on how endogenous testosterone and testosterone replacement therapy (TRT) affect cardiovascular physiology in men, particularly aging men and those with hypogonadism. The authors summarize a complex body of literature demonstrating that testosterone deficiency—not testosterone excess—correlates with increased cardiovascular risk, metabolic deterioration, and poorer overall prognosis .

The objective of this article is to translate these insights into a clear, structured, and scientifically engaging narrative. We will examine the physiology of testosterone relevant to cardiovascular function, analyse the evidence linking hypogonadism to heart disease, explore the mechanistic pathways through which testosterone influences cardiac and vascular tissues, and review the clinical data on TRT in various cardiovascular populations. The conclusion that emerges is not only interesting—it is counterintuitive: physiological testosterone appears cardioprotective, while deficiency aligns with poorer outcomes.

This realization challenges stereotypes and encourages clinicians to adopt an integrative, evidence-oriented approach when evaluating testosterone in male cardiovascular health.

The Physiological Roles of Testosterone in Cardiovascular Biology

Testosterone’s influence extends far beyond the testes. It binds androgen receptors in cardiomyocytes, vascular smooth muscle, endothelial cells, and numerous metabolic tissues. Its systemic reach means that cardiovascular physiology is inseparably intertwined with androgen signalling.

One of the central themes highlighted in the review is that testosterone plays an essential role in regulating vascular tone. Endothelial cells produce nitric oxide (NO), which relaxes smooth muscle and promotes vasodilation. Testosterone enhances NO production, improves endothelial responsiveness, and reduces vascular stiffness—features that contribute to optimal coronary perfusion and blood pressure control. Low testosterone, by contrast, is associated with increased arterial stiffness and impaired vasomotor function.

Testosterone also influences myocardial function. Through genomic and non-genomic pathways, it modulates calcium handling, mitochondrial efficiency, and contractile protein expression. These effects collectively support systolic performance. In heart failure patients, low testosterone correlates with reduced exercise capacity and poorer functional class. The review references studies demonstrating improved exercise tolerance in such patients receiving TRT, suggesting that testosterone acts as a metabolic support hormone in failing myocardium.

Finally, testosterone plays a significant role in body composition, promoting lean mass and suppressing visceral adiposity. Visceral fat is metabolically active and pro-inflammatory, contributing directly to atherosclerosis, insulin resistance, and systemic inflammation. Thus, testosterone deficiency facilitates the metabolic environment in which cardiovascular disease thrives. Repletion of testosterone shifts body composition toward a more favourable metabolic phenotype, indirectly benefiting the heart.

The message is clear: physiological testosterone levels contribute meaningfully to the maintenance of cardiovascular health, while deficiency destabilizes multiple protective systems.

Testosterone Deficiency as a Cardiovascular Risk Factor

One of the most striking insights from the review is the strong association between low testosterone levels and an increased risk of cardiovascular morbidity and mortality. This finding counteracts the historically popular belief that testosterone itself is harmful. Instead, evidence supports the concept that men with endogenous testosterone deficiency are more likely to develop coronary artery disease, heart failure, type 2 diabetes, obesity, and metabolic syndrome.

Multiple observational studies cited in the review demonstrate that low testosterone predicts:

increased all-cause mortality
increased cardiovascular mortality
higher rates of myocardial infarction and stroke
progression of heart failure
poorer outcomes in men undergoing coronary interventions

These associations persist even after adjusting for age, comorbidities, and baseline metabolic function. The evidence suggests that testosterone operates as a biomarker and potential mediator of cardiovascular resilience.

This relationship is bidirectional: chronic diseases such as heart failure, COPD, obesity, and diabetes all suppress testosterone production through alterations in the hypothalamic–pituitary–gonadal axis and inflammatory cytokine activity. The resulting hypogonadism further worsens metabolic and cardiovascular function, forming a vicious cycle.

Importantly, the review highlights that hypogonadism contributes to endothelial dysfunction—a precursor to atherosclerosis—by impairing NO-mediated vasodilation and promoting oxidative stress. It also accelerates insulin resistance, dyslipidemia, and visceral fat accumulation. These interlocking mechanisms explain why low testosterone is not merely associated with cardiovascular disease but intimately involved in its progression.

Taken together, the evidence positions hypogonadism as a clinically relevant cardiovascular risk factor—one deserving of screening and management in at-risk male populations.

Mechanisms Linking Testosterone to Cardiovascular Health

Understanding the mechanisms through which testosterone influences cardiovascular physiology is essential for evaluating its therapeutic potential. The review outlines several key mechanistic domains, each supported by empirical evidence.

Testosterone acts as a vasodilator, enhancing nitric oxide synthesis and potassium channel activation in vascular smooth muscle. This immediate, non-genomic effect lowers systemic vascular resistance, improves coronary blood flow, and may provide rapid symptomatic relief in men with angina. Several clinical studies show that acute testosterone administration improves time to ischemia during exercise testing.

The hormone also modulates lipid metabolism. Physiological testosterone levels tend to reduce total cholesterol and LDL while maintaining or slightly improving HDL. Testosterone deficiency promotes atherogenic lipid profiles, providing a clear biochemical pathway linking hypogonadism to atherosclerosis. Contrary to outdated assumptions, TRT does not cause clinically meaningful lipid deterioration when dosed appropriately.

Another vital mechanism involves glucose metabolism. Testosterone increases insulin sensitivity, reduces fasting glucose, and lowers hemoglobin A1c. These metabolic improvements play an essential role in reducing cardiovascular risk, as insulin resistance lies at the center of metabolic syndrome.

In myocardial tissue, testosterone supports contractile performance by enhancing calcium cycling, mitochondrial respiration, and protein synthesis. These effects are particularly relevant to heart failure patients, who often exhibit skeletal muscle wasting, fatigue, and reduced cardiopulmonary capacity. Low testosterone exacerbates these deficits.

Finally, testosterone exerts anti-inflammatory effects, suppressing cytokines such as TNF-α and IL-6. Chronic inflammation contributes to endothelial dysfunction and plaque instability; thus, testosterone’s immunomodulatory properties may support cardiovascular stability.

Altogether, these mechanisms describe a multifaceted network through which testosterone supports cardiovascular integrity. They also illustrate why deficiency creates an environment primed for disease.

Testosterone Replacement Therapy and Cardiovascular Outcomes

The central clinical question addressed by the review is whether testosterone replacement therapy (TRT) is safe for men with or at risk for cardiovascular disease. Historically, TRT was approached with caution based on concerns about thrombosis, polycythemia, and potential exacerbation of coronary disease. However, contemporary evidence challenges these concerns.

According to the authors, clinical trials and meta-analyses demonstrate that TRT, when administered to hypogonadal men within physiological dosing ranges, does not increase cardiovascular events. In fact, many studies report improved symptoms, metabolic markers, and even reduced mortality.

Heart failure patients appear particularly likely to benefit. Randomized trials show that TRT improves:

exercise capacity
ventilatory efficiency
peak oxygen consumption
muscle strength
overall functional class

These benefits are likely mediated by improved muscle metabolism, enhanced erythropoiesis, and vasodilatory effects.

In men with coronary artery disease, TRT has demonstrated anti-ischemic benefits by improving coronary perfusion. The review notes that men treated with testosterone exhibit prolonged exercise time before the onset of angina, suggesting an improvement in myocardial oxygen supply-demand balance.

Concerns regarding thrombosis and polycythemia are valid but manageable. Polycythemia risk increases with higher doses of testosterone or in men predisposed to erythrocytosis, but careful dosing and routine hematocrit monitoring maintain safety. Similarly, no strong evidence supports a connection between TRT and major adverse cardiovascular events when therapy is properly supervised.

Thus, the review’s conclusion is unambiguous: in appropriately selected men with documented hypogonadism, TRT is safe and may confer cardiovascular benefit.

Addressing the Controversies: Understanding the Past Misconceptions

Despite the robust evidence supporting testosterone’s neutral or beneficial cardiovascular effects, controversy persists, largely due to earlier studies with methodological limitations. The review outlines that early observational studies suggesting harm suffered from confounding variables, improper patient selection, retrospective design, and non-standardized testosterone dosing.

Several high-profile studies that triggered regulatory concern involved frail elderly patients with multiple comorbidities who received supraphysiologic dosing or nontherapeutic formulations. Some data sets aggregated men prescribed testosterone with men who were merely evaluated for it, artificially inflating event rates.

More rigorous studies, including randomized controlled trials, corrected these flaws and found no increase in cardiovascular events. Modern consensus statements now emphasize that TRT is safe when prescribed correctly. Still, clinicians should remain vigilant, as misuse, unsupervised administration, and excessively high serum levels pose legitimate risks.

The authors highlight the importance of:

selecting genuine hypogonadal patients
targeting physiological—not supraphysiologic—levels
monitoring hematocrit, PSA, and cardiovascular status
avoiding TRT in men with unstable cardiovascular disease

This balanced approach reconciles safety concerns with therapeutic opportunity.

Testosterone Therapy in Special Cardiovascular Populations

Not all patient populations respond to TRT equally. The review discusses outcomes in specific cardiovascular contexts.

Men with heart failure often exhibit low testosterone as a biomarker of disease severity. TRT improves exercise tolerance and metabolic efficiency, making it a promising adjunct therapy. However, long-term mortality data are still limited.

Men with coronary artery disease experiencing angina may benefit from testosterone’s vasodilatory action. The review notes improved exercise test performance, though the long-term impact on atherosclerosis remains under study.

In men with obesity and metabolic syndrome, TRT improves insulin sensitivity and lipid profiles, conferring indirect cardiovascular benefit. These metabolic shifts can reduce overall cardiovascular risk burden.

Patients with hypertension may also benefit from testosterone’s vasodilatory effects, although the magnitude of blood pressure reduction is modest.

Overall, TRT demonstrates clinically meaningful improvement in symptoms and surrogate markers across these populations, though long-term outcome studies remain needed.

Conclusion

The review “Testosterone and the Heart” challenges long-standing misconceptions by presenting compelling evidence that physiological testosterone is not detrimental, but rather integral to cardiovascular health. Testosterone deficiency correlates with endothelial dysfunction, metabolic syndrome, ischemic heart disease, heart failure, and increased mortality. Conversely, testosterone replacement therapy, when used appropriately, appears safe and may improve multiple cardiovascular parameters, including exercise tolerance, glucose metabolism, and coronary perfusion.

The hormone’s effects are multifaceted—ranging from vasodilation and lipid modulation to anti-inflammatory activity and improved myocardial contractility. These actions collectively support cardiovascular function rather than compromise it. As clinical practice evolves, testosterone should be viewed not as a cardiovascular threat but as a physiological ally in properly selected patients.

The overarching lesson is that endocrinology and cardiology are inseparable disciplines, and testosterone represents a crucial bridge connecting them. Clinicians must therefore approach testosterone deficiency with seriousness, nuance, and evidence-driven decision making.

FAQ

1. Does testosterone therapy increase the risk of heart attack or stroke?

Current evidence shows that physiological testosterone replacement does not increase cardiovascular risk in hypogonadal men when properly monitored. Most concerns originated from flawed early studies.

2. Is low testosterone really linked to heart disease?

Yes. Low testosterone is associated with higher rates of coronary artery disease, heart failure, metabolic syndrome, and overall mortality. It is increasingly recognized as a cardiovascular risk factor.

3. Can testosterone therapy improve heart function?

In hypogonadal men with heart failure or angina, testosterone therapy may improve exercise capacity, vascular function, and myocardial efficiency. Benefits depend on proper dosing and patient selection.