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By William Llewellyn

Testosterone and the Heart— A New Era?

If you are a man, at some point in your life you are likely to be a candidate for hormone replacement therapy. As we age, our testosterone levels decline, and with them often a number of physical and psychological characteristics. It has long been understood that low testosterone levels can be linked to reduced libido, sexual dysfunction, diminished energy, and a reduced overall sense of well-being. For these reasons, replacement therapy with testosterone drugs is a strong and steadily growing area of medicine for aging men.

Beyond these basic facts, testosterone remains a controversial drug. Its abuse is linked to changes in the body that may increase the likelihood of cardiovascular disease, and partly because of this, the potential benefits and risks of testosterone replacement therapy have long been the subject of much debate. Is this therapy actually safe?

In recent years, evidence has been surfacing that testosterone replacement may actually reduce cardiovascular disease risk. Usually isolated in scope, these papers concern many favorable changes in cardiovascular health markers, such as the management of triglycerides and cholesterol. I believe I’ve discussed some of these papers in this column before. Hopefully, a paper published in the Journal of Andrology will further this discussion a great deal.

This 37-page report entitled “The Dark Side of Testosterone Deficiency” is the third in a series of papers covering the potential benefits of hormone replacement therapy in men.1 It specifically reviews the mounting evidence in favor of the use of testosterone for reducing heart disease risk, addressing the most detailed and relevant studies on the subject. This is the most extensive paper on testosterone therapy and heart disease to date, and covers several specific potential benefits.

Growing evidence suggests that testosterone administration may actually reduce the risk of heart disease in older men.

Serum Lipids

One of the first potential benefits of testosterone replacement therapy (TRT) reviewed in this paper is the management of triglyceride and cholesterol levels. As detailed in a growing number of studies, testosterone replacement therapy consistently improves the lipid profile in men with hormone deficiency. The most consistent endpoints of improvement appear to be a reduction in total cholesterol, a reduction in LDL (‘bad’) cholesterol, and a lowering of serum triglycerides. The improvements in lipid profile appear to be more pronounced in older men, although both young and old populations tend to show improvements in serum lipids when testosterone is given to correct a deficient state.

The effect of TRT on HDL (‘good’) cholesterol levels is less consistent. Studies giving testosterone gels, patches, or the longest-acting ester (testosterone undecanoate) tend to show improvement or no consistent effect on HDL. Studies with the more common esters such as cypionate and enanthate tend to show minor decreases in HDL during therapy, likely owing to the brief supraphysiological peaks for several days after administration. Note that HDL is often improved when TRT is combined with exercise and other lifestyle modifications.

Inflammatory Markers

Androgen deficiency is associated with an increase in certain inflammatory markers that can support the progression of atherosclerosis. Testosterone replacement therapy has been shown to reduce some of the same inflammatory mediators, specifically TNF-alpha (tumor necrosis factor-alpha) and IL-1B (interleukin-1beta).

Inflammation in the vascular system is an especially important concern with heart disease. For one, vascular inflammation is associated with the deposition of arterial plaque, a key component of this disease. Inflammation of the blood vessels may also damage the arteries, making them both thicker and weaker. Scarring may be noticed, and blood flow may be reduced. All of this can restrict blood flow and reduce the heart’s blood pumping capacity.

By helping to reduce the production of TNF-alpha and IL-1B, hormone replacement therapy may reduce inflammation, vascular damage, and the chance for atherosclerosis. Again, instead of seeing a neutral or ‘negative’ effect, we find a specific improvement in the cardiovascular disease risk profile with the administration of this drug.

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