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.