Testosterone replacement therapy and aneurysm biology: current evidence and clinical implications

Abstract Background Testosterone replacement therapy (TRT) is increasingly used to treat male hypogonadism, but its role in aneurysm biology remains unclear. Because aneurysm formation is driven by inflammation, extracellular matrix degradation, and vascular remodeling, testosterone may influence disease progression through androgen receptor–mediated pathways. Methods A narrative literature review was conducted using PubMed/MEDLINE, EMBASE, and Google Scholar (August–September 2025). Studies examining testosterone, TRT, vascular inflammation, and aneurysm-related outcomes, including experimental, preclinical, and clinical studies, were included. Evidence synthesis Available evidence is mostly mechanistic and preclinical. Animal studies indicate vascular bed-specific effects: physiological androgen signaling seems protective in abdominal aortic aneurysm models by reducing macrophage infiltration and inflammatory cytokine signaling, whereas exogenous or supraphysiologic testosterone may exacerbate oxidative stress and vascular injury in intracranial aneurysm models. Human data remain indirect, with no prospective studies specifically assessing aneurysm formation, growth, or rupture in TRT users. Large randomized trials and meta-analyses indicate cardiovascular safety comparable to placebo in appropriately selected patients, though higher rates of atrial fibrillation, pulmonary embolism, and erythrocytosis have been reported. Conclusion Testosterone has context-, dose-, and vascular bed-specific effects on aneurysm biology. Until clinical studies on aneurysm outcomes are available, TRT should be individualized, dosed to meet physiological needs, and closely monitored for cardiovascular and vascular health. No evidence-based recommendation can currently be made to initiate, withhold, or modify TRT solely on the basis of aneurysm status. Multidisciplinary discussion and continued standard aneurysm surveillance are advisable for hypogonadal patients with known aneurysmal disease.