Testosterone and the Heart— A New Era?

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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.

[ANDROGEL PICTURE] 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.

Abdominal Obesity, Insulin Resistance

A growing number of studies have linked androgen deficiency to insulin resistance, as well as increased abdominal obesity. These two factors are also common with men suffering from cardiovascular disease, and may directly contribute to (among other things) endothelial cell dysfunction and vascular damage. Androgen substitution has been shown in several studies to reduce midsection fat deposits, increase glucose tolerance, and improve the overall metabolic state. It has additionally been postulated that due to the important role of testosterone in managing insulin sensitivity, androgen deficiency may be a contributing factor to adult-onset (type 2) diabetes. Likewise, the substitution of testosterone in aging men with hypogonadism might reduce the likelihood of developing diabetes.

Endothelial Function

The endothelium is a layer of cells that lines the blood vessels throughout the entire circulatory system. These cells are responsible for managing the passage of some materials in and out of the blood vessels, and supporting the flow of blood through the system. Endothelial cells play a role in vasoconstriction and vasodilation, they regulate certain inflammatory processes, and they’re involved in blood clotting and in supporting the formation of new blood vessels. Endothelial dysfunction is linked to androgen deficiency in men, and may result in elevated blood pressure (hypertension), vascular ‘stiffness,’ and significantly increased risk of cardiovascular disease. Likewise, replacement of testosterone in men with a deficiency has been shown to improve endothelial function, blood vessel dilation, arterial vasoreactivity, and blood flow.

One additional important ‘endpoint’ of improvement to this therapy appears to be an increase in endothelial progenitor cell activity, which helps repair damage to the vascular system.

Conclusion

Traditionally, most physicians are extremely cautious with testosterone drugs. Many family doctors are very willing to prescribe estrogens to their female menopausal patients complaining of symptoms such as sexual dysfunction, but when it comes to their male patients with similar complaints, the response is often different. Many of these same physicians are much more willing to prescribe a drug like Viagra than the basic male androgen testosterone. Some mistakenly consider testosterone to be ‘too dangerous’ to give most of their patients, and reserve its use for extreme cases. And when testosterone is considered, it is given only for a very narrow and specific set of psychological or physical symptoms.

Of course in the era of AndroGel, some physicians are much more enlightened. Still, the troubling common fear of this hormone remains. Perhaps this is changing, and perhaps the accepted set of symptoms and therapies for prescribing this hormone is changing.

It seems clear that we can no longer paint testosterone as simply a ‘bad’ hormone for the cardiovascular system. While excessive high-level elevations of this hormone may indeed damage an individual’s cardiovascular health, we have strong evidence that within a certain physiological range, it may also protect the cardiovascular system from some of the same health issues. As such, its replacement may indeed turn out to be very important medical intervention for millions of men across the country, helping us to not only live better— but also live longer.

After all this time, it appears that this very controversial hormone, the same steroid demonized in the media, might actually help reduce the risk of cardiovascular disease in aging male patients. The study we reviewed this month is, likewise, something all men should take to heart— literally.

Reference:

1.The Dark Side of Testosterone Deficiency: III. Cardiovascular Disease. Traish AM, Saad F et al. Journal of Andrology, April 2, 2009. ePub, Ahead of Print.

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