Not enough test in testosterone

(This article was first printed in the April, 2004 issue of the Harvard Heart Letter. For more information or to order, please go to http://health.harvard.edu/heart.)

More and more men are turning to testosterone therapy even though little is known about its effects on the heart and long-term health.

If aging causes a gradual droop in a man’s production of testosterone, can boosting levels of this hormone restore youthful vitality, or at least slow aging and prevent the diseases that come with it? The million or so men now taking testosterone certainly hope so.

By age 60, about one in five men have testosterone levels below what’s normal for young men. Whether their levels are too low for men of their age is still a big unknown. Having less testosterone in the bloodstream could protect men against prostate cancer or other testosterone-related diseases. It could also pose problems.

Testosterone, sometimes erroneously called the male hormone (women’s bodies make it, too) affects much more than a man’s sex drive, hair pattern, and prostate. It helps build muscle and metabolize fat. It strengthens bone. It can also boost energy and mood, and may play a role in memory.

These possible benefits, coupled with the siren song of looking and feeling younger, are calling a growing number of older men to try testosterone therapy. For those whose bodies make too little of the hormone, it’s the right thing to do. For everyone else, testosterone therapy is an unplanned, uncontrolled, unsupervised experiment.

We say this because no one knows if extra testosterone improves health or well-being in men with normal or low-normal levels of the hormone. More alarming, there’s no clear picture of the hazards (see How taking testosterone could affect the body). How testosterone therapy affects the heart, blood vessels, and circulation is another gray area.

Hormones and the heart

For years, testosterone was blamed for the earlier appearance of heart disease in men than in women. Yet studies now suggest the opposite possibility: that testosterone could be good for men’s hearts. Some studies, but not all, have linked higher testosterone levels with higher levels of HDL (good) cholesterol, lower blood pressure, better natural clot-busting ability, greater sensitivity to insulin, and less inflammation. Men with more testosterone seem to be less likely to develop atherosclerosis (the process leading to cholesterol-clogged arteries) and diabetes than men with lower levels.

Among men with too little testosterone, regular doses that bring the hormone into the normal range don’t harm cholesterol levels or blood pressure. Some small but intriguing studies suggest that testosterone therapy can improve the flexibility of arteries, ease activity-related chest pain (angina), and improve heart function among men with heart failure.

Lessons from women

If this paints a positive, why-not-start-today picture of testosterone therapy, the flip-flop on hormone therapy in women should raise a red flag.

During the 1990s, women were encouraged to take estrogen after menopause to help prevent heart disease. This recommendation was based on two consistent streams of evidence. In several studies that followed the health of large groups of women for up to a decade or longer, those who chose to take estrogen had fewer heart attacks or strokes than those who didn’t take hormones. At the same time, smaller experiments showed that estrogen improved cholesterol levels, blood vessel flexibility, and natural anticlotting ability.

Yet when large trials in which volunteers took an unmarked pill containing estrogen plus progestin or a placebo finally got under way, women who took the hormones had more heart attacks, strokes, serious blood clots, and new cases of breast cancer.

This won’t necessarily happen with testosterone. But we can’t be sure how this hormone affects the heart without the same kind of randomized trials that revealed possible problems with hormone therapy in women.

What to do

Such trials haven’t yet gotten off the drawing board, and the Institute of Medicine has recommended putting them on hold. So it could be five years or longer before the true benefits and risks begin to firm up.

What should you do in the meantime? If you aren’t taking testosterone, don’t start unless your body needs it and you have symptoms that suggest a testosterone problem. Tip-offs include fatigue, muscle weakness, dwindling interest in sex, osteoporosis, or a suspicious bone fracture. A simple early-morning blood test (possibly repeated once or twice) can tell you how much testosterone is circulating in your blood. A low reading may prompt your doctor to check for possible causes. These may include problems with the pituitary gland or the part of the brain called the hypothalamus, both of which regulate testosterone production. Some doctors use 200 nanograms per deciliter (ng/dL) as a cutoff, while others use 300–400 ng/dL.

If your testosterone is indeed low, Drs. Ernani Rhoden and Abraham Morgentaler, from Harvard-affiliated Beth Israel Deaconess Medical Center, suggest some steps to take before starting therapy. They recommend having a prostate exam along with blood tests for red blood cells and prostate-specific antigen (PSA, a test for prostate cancer). They also urge their older patients to have a prostate biopsy to check for hidden prostate cancer. These recommendations appeared in their review of testosterone therapy in the January 29, 2004, New England Journal of Medicine.

Once you start taking testosterone, itR 17;s important to monitor how your body responds to it. Are blood levels of the hormone rising? Are symptoms improving? Have you noticed changes in your urination, or are you snoring more? Routine follow-up should include rectal exams for prostate cancer and periodic blood tests for PSA and hematocrit (red blood cells). Because the effects of testosterone therapy on the heart and circulatory system are unknown, paying more attention to the warning signs of a heart attack or stroke may also be in order.

If you are taking testosterone even though your level is in the normal range, there’s no urgent need to stop. You might want to revisit the benefits and risks with your doctor, though, and keep alert for possible problems. In other words, approach testosterone therapy like the experimental treatment it is, open to the possibility of benefit and alert for the possibility of harm.