Lown Cardiovascular Research Foundation

Harvard Heart Letter | March 2008

Focus on hormones

Testosterone therapy’s benefits, risks need crystallizing

In older men, low testosterone may contribute to heart disease, diabetes, and other chronic conditions.

Testosterone, the most male of hormones, profoundly affects the heart. In young men, it nudges the heart (and other parts of the body) toward romance. In older men, it helps keep the heart ticking and blood vessels in shape for love and everything else.

Testosterone was once thought to be bad for the heart, a key culprit behind the tendency of heart disease to appear earlier in men than in women. But a growing body of research indicates that for older men, it’s too little testosterone that poses problems, cardiovascular and otherwise.

Two large studies published in 2007, one from California and one from England, suggest that men with low testosterone don’t live as long as those with normal levels. Heart disease and stroke were leading causes of death in both studies. But even after the researchers accounted for age, illness, cholesterol, smoking, obesity, and other factors, low testosterone still stood out as a key connection to heart disease.

These intriguing results add to the mounting evidence linking low testosterone to the development of cardiovascular disease, type 2 diabetes, and other chronic conditions in men. But they don’t answer a key question about the hormone: Does boosting testosterone lengthen life or prevent heart disease?

Testosterone and the ticker

Cells in the heart and blood vessels carry receptors for testosterone. Precisely how this so-called sex hormone affects these cells has yet to be pinned down. It’s known that testosterone helps blood vessels relax, widen, and carry more blood when needed. It improves blood pressure and cholesterol levels and may positively influence electrical conduction in the heart. Testosterone is also somehow involved in helping muscle cells respond to insulin’s signal to absorb blood sugar.

With all this going for testosterone, it’s too bad that production of the hormone usually peaks before age 25 or so. After that, it’s all downhill, with a 1% to 2% decline each year. Most men have a normal testosterone level for life. What defines “normal,” though, is still unsettled. For younger men, it’s a total testosterone level above 300 nanograms per milliliter of blood. Whether older men should be held to that same standard, or a lower one, is up in the air. Low testosterone production, a condition known as hypogonadism, can cause problems ranging from anemia to flagging interest in sex (see “Hazards of low testosterone”).

Testing testosterone

It is relatively easy for a man to raise his testosterone level. A weekly or biweekly injection of the hormone; applying a testosterone gel daily to the upper arms, shoulders, or abdomen; or keeping a testosterone lozenge tucked next to the cheek and gums all do the trick. So if a low level poses cardiovascular and other problems, why not just give it a boost?

Alarming results from trials of estrogen therapy in older women urge caution. Instead of preventing heart disease, as many experts had predicted, estrogen supplements increased the risk of heart disease, stroke, and blood clots. Conflicting findings from testosterone trials in men don’t help matters much. The latest, a six-month study in 200 Dutch men with borderline low testosterone, showed that boosting testosterone increased muscle mass and sensitivity to insulin but decreased protective HDL and had little effect on thinking or memory skills and quality of life. The test was too short to detect an effect on heart disease or prostate cancer. The results were published in the Jan. 2, 2008, issue of the Journal of the American Medical Association.

It is entirely possible that testosterone therapy could offer some protection against heart disease, weakened bones, and type 2 diabetes. But there are worries that it could also promote prostate cancer, negatively affect cholesterol levels, or increase the blood’s tendency to clot. Whether the research needed to answer such questions will get off the ground is anyone’s guess.

What to do now

Excellent advice comes from the Endocrine Society, which represents doctors who specialize in understanding and treating hormonal problems. The society doesn’t believe that testosterone checks should be part of all men’s medical care, like blood pressure and cholesterol measurements. Instead, men with signs or symptoms of low testosterone should have an early-morning blood test for the hormone. If it is low, then testosterone therapy makes sense. But it shouldn’t be used as a tonic or pick-me-up by men whose bodies are making enough of the hormone.