Cardiovascular Disease

Cardiovascular disease encompasses conditions like atherosclerosis, heart attacks, and heart failure that impair heart and blood vessel function, often stemming from factors such as plaque buildup, inflammation, and poor metabolic health. In the context of low testosterone, particularly in men, it is associated with elevated risks including insulin resistance, dyslipidemia, and increased all-cause mortality, potentially exacerbating these issues without directly causing them.

Bidirectional Link: Low Testosterone ↔ Cardiovascular Disease

Low testosterone → cardiovascular disease: Reduced vasodilation → testosterone has direct relaxing effects on blood vessels. Increased blood pressure → low testosterone correlates with systolic and diastolic hypertension. Worsened lipid profile → lower HDL, higher triglycerides. Increased atherosclerosis → decreased arterial elasticity and endothelial function. Increased inflammatory markers → chronic inflammation promotes cardiovascular damage.

Cardiovascular disease → low testosterone Cardiovascular medication can affect testosterone production. Chronic disease and stress suppress hypothalamic-pituitary-gonadal axis. Reduced physical activity due to heart problems → further declining testosterone. Systemic inflammation disrupts hormonal signaling pathways.

Vicious circle: Low testosterone → cardiovascular risk factors → cardiovascular disease → further hormonal disruption

Effect of TRT

Overall Safety: TRT does not increase major cardiovascular events, heart attacks, strokes, or cardiovascular deaths in men with low testosterone
Mortality Benefits: TRT may reduce all-cause mortality risk by 35-44% compared to untreated low testosterone
Arrhythmia Risk: Modest increase in atrial fibrillation and heart rhythm problems observed in some large studies
Secondary Effects: Small increases in kidney issues and blood clots noted but overall cardiovascular safety profile remains favorable
Study Quality: Conclusions supported by multiple large randomized controlled trials involving over 20,000 participants across recent meta-analyses
Risk-Benefit: Benefits of preventing cardiovascular mortality from untreated low testosterone appear to outweigh small increased risks of non-fatal complications

Based on multiple recent meta-analyses of randomized controlled trials involving over 20,000 participants, the evidence shows moderate-to-strong quality that TRT does not increase cardiovascular disease risk and is cardiovascularly safe in men with low testosterone. However, the evidence for TRT actively reducing cardiovascular disease is limited, as most high-quality studies demonstrate cardiovascular neutrality rather than protective effects, with the primary benefit being prevention of the increased mortality risk associated with untreated low testosterone.

Serum Total Testosterone and Premature Mortality Among Men in the USA (PMC8317905) (2021) (Cohort Study)

Men with low testosterone (<300 ng/dL) face over twice the risk of early death.
Cardiovascular issues are a main cause of this increased mortality risk.
The study highlights low testosterone as a key factor in overall health decline.

Endogenous Testosterone and Mortality in Men: A Systematic Review and Meta-Analysis (PMC3200249) (2011) (Meta-Analysis)

Low natural testosterone levels link to higher heart disease and overall death risks.
Risk increases by 25-35% for men with low testosterone.
Findings are consistent across multiple studies on men's health.
Low testosterone may signal broader health problems leading to mortality.

Low testosterone in men predicts impaired arterial elasticity and microvascular function (PMC9135451) (2022) (Observational Study)

Low testosterone predicts stiffer arteries and poorer small blood vessel function.
This raises overall heart disease risk in affected men.
The issues may contribute to long-term cardiovascular problems.

Predictive value of low testosterone concentrations regarding coronary heart disease and mortality in men and women – evidence from the FINRISK97 study (PMC6851597) (2019) (Cohort Study)

Low testosterone does not predict future heart disease or death in men or women.
No strong link found between testosterone levels and cardiovascular outcomes.
Results challenge assumptions about low testosterone's role in heart health.

Age-associated reductions in cardiovagal baroreflex sensitivity are exaggerated in middle-aged and older men with low testosterone (PMC9359637) (2022) (Observational Study)

Low testosterone worsens age-related drops in heart rate regulation.
This increases risks for heart events in older men.
The effect is more pronounced with both aging and low testosterone.

Cardiovascular Safety of Testosterone-Replacement Therapy (37326322) (2023) (RCT)

Testosterone therapy is as safe as placebo for major heart events in men with low testosterone and heart risks.
No increase in heart attacks, strokes, or heart-related deaths.
Higher rates of irregular heartbeats, kidney issues, and lung clots observed.
Study involved over 5,000 men followed for about 3 years.

Association between testosterone replacement therapy and cardiovascular disease: A meta-analysis of 30 randomized controlled trials (38589271) (2024) (Meta-Analysis of RCTs)

Testosterone therapy does not raise heart disease risk or overall death rates in men with low testosterone.
No differences in strokes, heart attacks, or heart-related deaths compared to placebo.
Analysis of 30 studies with over 11,000 participants supports safety.

Testosterone Replacement Therapy and Cardiovascular Outcomes: A Meta-analysis of Randomized Controlled Trials (40694252) (2025) (Meta-Analysis of RCTs)

Testosterone therapy does not increase overall death, heart-related death, strokes, or heart attacks in older men with low testosterone.
It does raise the risk of heart rhythm problems.
Review of 23 studies with over 9,000 men confirms general safety but notes arrhythmia concern.

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