Testosterone is the primary male sex hormone, an androgen that influences muscle mass, bone density, and reproductive function. Arterial plaque, formally known as atherosclerosis, describes the buildup of fatty deposits within the walls of arteries throughout the body. The question of whether testosterone contributes to plaque formation and subsequent cardiovascular disease has been a long-standing subject of scientific investigation. Clarifying this relationship requires examining the distinct effects of naturally occurring testosterone levels versus those achieved through therapeutic hormone administration.
Understanding Arterial Plaque
Arterial plaque is a complex deposit that develops slowly over many years, primarily composed of fat, cholesterol, calcium, and cellular waste products. Atherosclerosis begins when the endothelium, the inner lining of an artery, sustains damage from factors like high blood pressure or smoking. This injury triggers a defensive inflammatory response in the arterial wall.
The inflamed area becomes a site for low-density lipoprotein (LDL) cholesterol particles to accumulate and become trapped beneath the endothelial surface. Immune cells called monocytes migrate to the site and transform into macrophages, which then consume the trapped cholesterol, becoming “foam cells.” These foam cells contribute to the growing, soft core of the plaque.
As the condition progresses, smooth muscle cells migrate to the site and lay down a fibrous cap over the fatty core, attempting to stabilize the lesion. This fibrous cap separates the plaque from the flowing blood inside the artery. A rupture of this cap can expose the core material to the bloodstream, triggering a blood clot that may partially or completely block the vessel, leading to a heart attack or stroke.
Testosterone’s Role in Vascular Health
Testosterone acts as a vasoactive hormone, directly influencing the tone and diameter of blood vessels. It has demonstrated vasodilatory actions, promoting the relaxation of arterial smooth muscle cells to help regulate blood flow and pressure. This effect is mediated by the hormone’s interaction with androgen receptors located within the vascular tissue.
The hormone also influences cardiovascular risk factors, including body composition. Testosterone generally favors the development of lean muscle mass over adipose tissue, and low body fat is associated with better vascular outcomes. Furthermore, testosterone appears to possess anti-inflammatory and antioxidant properties, which help protect the endothelium from the initial damage that triggers plaque formation.
Testosterone’s influence on the body’s lipid profile is complex, but some evidence suggests it can affect the balance of high-density lipoprotein (HDL) and LDL cholesterol. Its general physiological presence supports a healthier environment for the arterial system. Its metabolites, such as dihydrotestosterone, also contribute to these direct effects on the vascular wall.
Examining the Link Between Testosterone Levels and Atherosclerosis
Contrary to the common concern that the male sex hormone actively causes plaque, a large body of evidence suggests that low endogenous testosterone levels are associated with increased cardiovascular risk and accelerated atherosclerosis. Observational studies have found an inverse relationship between a man’s natural, circulating testosterone level and the risk or progression of severe atherosclerosis. Men in the lowest quartile of total testosterone levels have shown a significantly increased likelihood of cardiovascular mortality.
This link between low testosterone and poor vascular health is hypothesized to stem from the hormone’s absence contributing to a pro-atherosclerotic environment. Low levels are frequently correlated with known risk factors for plaque buildup, such as increased abdominal fat, insulin resistance, and poor metabolic control. The deficiency may also lead to heightened oxidative stress and chronic inflammation within the arterial wall, encouraging the initial steps of plaque development.
While some studies have conflicting results, the overall consensus is that physiological levels of testosterone may be protective. For instance, analyses have reported an inverse association between testosterone levels and the total carotid plaque area in cross-sectional studies. This suggests that maintaining testosterone within a healthy, normal range is more likely to be beneficial for arterial health than detrimental.
Clinical Considerations for Testosterone Therapy
The question shifts when considering exogenous testosterone replacement therapy (TRT), as administering the hormone can elevate levels beyond a man’s natural range. Clinical trials investigating TRT’s effects on plaque progression have yielded mixed results, prompting caution in its use. One study in older men with low testosterone found that one year of treatment was associated with a significantly greater increase in non-calcified coronary artery plaque volume compared to a placebo group.
However, a large-scale clinical trial (TRAVERSE) focusing on men with hypogonadism and a high risk of cardiovascular events provided reassurance. It found that TRT was noninferior to placebo regarding the primary endpoint of major adverse cardiovascular events. This suggests that for men with true hypogonadism, the overall risk of heart attack or stroke may not be significantly increased by therapy.
The TRAVERSE trial did note a higher incidence of specific risks, including pulmonary embolism and atrial fibrillation, in the testosterone group, highlighting the need for careful risk assessment. For patients undergoing therapy, monitoring is important, especially for hematocrit levels, as TRT can increase red blood cell production, potentially leading to polycythemia. Physicians must weigh the benefits of symptom relief against the potential for adverse effects, particularly in men with pre-existing cardiovascular conditions.