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Harvard Commentaries
Harvard Commentaries
Reviewed by the Faculty of Harvard Medical School

Man to Man Man to Man

Testosterone -- The 'Heart' of the Matter

January 24, 2013

By Harvey B. Simon M.D.

Harvard Medical School

Forget clothes. In a very real sense, testosterone makes the man. It:

  • Gives us the deep voice, large muscle mass and strong bones that characterize our gender
  • Stimulates the production of red blood cells by the bone marrow
  • Contributes to aggressiveness
  • Is essential for the libido or sex drive, as well as for normal erections and sexual performance
  • Stimulates the growth of the genitals at puberty and helps produce sperm
  • Can lead to acne, put hair on the chest — or take it off the scalp — after the hormone is converted to dihydrotestoterone (DHT)

DHT also stimulates the normal growth of prostate cells in adolescents but contributes to benign prostatic hyperplasia (BPH) — and perhaps prostate cancer — in many older men.

So while these effects on the body are well-known, new research is challenging old assumptions about how the hormone affects a man's heart, circulation and metabolism.

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What We Know

For years, doctors have worried about a link between testosterone and heart disease. This is largely because men have much more testosterone than women, and they develop heart disease about 10 years before women. But we also know that:

  • Animals given testosterone develop enlarged hearts
  • Athletes who abuse testosterone and other androgenic steroids have a sharply increased risk of high blood pressure, heart attack and stroke
  • In high doses, testosterone can raise LDL ("bad") cholesterol and lower HDL ("good") cholesterol levels

There is no doubt that high doses of testosterone are bad for the heart and for cholesterol levels. But what about normal doses?

When doctors from the Mayo Clinic recently reviewed 30 clinical trials of normal-dose testosterone replacement therapy, they did not find any overall effect of hormone treatment on cholesterol levels, for better or worse. (Men who have a testosterone deficiency — called hypogonadism — are given replacement therapy. This condition can be due to genetic errors, mumps, severe trauma, alcoholism, cancer chemotherapy and radiation, and other, less common conditions.)

We have less information about how testosterone affects other heart disease risk factors. But it doesn't appear linked to diabetes, obesity, hypertension, heart-harmful inflammation or high levels of homocysteine (an amino acid linked to heart disease and stroke).

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Could Testosterone Therapy Be Good for a Man's Heart?

Just because large doses of testosterone harm the heart and metabolism doesn't necessarily mean that normal amounts are also harmful. Is it possible that testosterone therapy could help men with heart and blood vessel disease?

Only a few small, short-term studies so far suggest any answers, and their results are mixed.

  • A 2000 trial evaluated 46 men with mild angina (chest pain) and low-normal blood testosterone levels. They were randomly assigned to 12 weeks of treatment with a testosterone patch or a placebo patch. Each man took an exercise stress test on a treadmill before and after treatment. Compared with the placebo-treated subjects, the men who got testosterone increased their treadmill time by an average of 26 seconds on the repeat stress test.
  • A 2004 study of 10 men with angina and low testosterone levels found that after one month, men who received testosterone shots gained 74 seconds on the treadmill test compared with similar men who got placebo shots. The testosterone did not change HDL ("good") or LDL ("bad) cholesterol levels.
  • In a 2008 study, 25 men with heart disease took either a testosterone pill or a placebo pill. The testosterone modestly increased blood flow to the heart muscle by widening healthy coronary arteries that showed no blockages. Testosterone also boosted heart-muscle contractions. However, treatment had no effect on angina and it did lower HDL ("good") cholesterol levels.

The real question is whether testosterone therapy can change a man's risk of having a heart attack, stroke or blood clot. Mayo Clinic scientists reviewed six trials that together included 147 men who received placebos and 161 who received testosterone for up to three years. The testosterone did not change the risk of these events for better or worse.

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Testosterone Tinkering

Testosterone deficiency (hypogonadism) affects about 6% of American men. Most are older. If the Institute of Medicine's estimates are correct, about 250,000 American men are receiving testosterone for this condition. This is the only condition for which the hormone is approved for use by the U.S. Food and Drug Administration (FDA).

But some 1.75 million prescriptions for testosterone products were written by American doctors in 2002 — at a cost of $400 million — and the numbers have continued to soar. Why are all these men taking testosterone? And should they?

Heart disease is not the only thing that's linked to aging. As the years pile on, men experience declines in:

  • Muscle mass and bone density
  • Red blood cells
  • Sexual desire
  • Mood
  • Energy
  • Memory

The only thing that goes up is body fat. In theory, at least, testosterone therapy might weaken or reverse each of these woes.

This makes testosterone sound pretty good. It's why so many men are turning to the drug. But the theoretical benefits should be balanced against theoretical risks.

The most serious long-term risks of testosterone therapy are benign prostatic hyperplasia (BPH) and prostate cancer. Other potential side effects include polycythemia (an excessive number of red blood cells), sleep apnea (breathing pauses during sleep that may increase the risk of high blood pressure, heart attack and stroke), gynecomastia (benign breast enlargement), acne and liver disease.

Nobody knows if the potential gains of testosterone treatment outweigh the possible pains. To date, only small, short-term studies have been completed. They report few side effects but also few benefits.

More research is needed to learn how testosterone affects the heart and the rest of a man's body and mind. Because of the Women's Health Initiative, medical "wisdom" was turned on its ear when the large study reported that hormone replacement therapy does more harm (breast cancer, heart attacks and strokes) than good, particularly for older women. Because of the possible risks of long-term testosterone therapy, however, a "Men's Health Initiative" is not in the works.

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The Bottom Line

Without good data, what's a guy to do? The best advice is to protect your heart and your body by reducing or eliminating risk factors such as cholesterol, blood pressure, diabetes, obesity and tobacco exposure.

Don't forget that diet and exercise are still the keys to:

  • Lowering heart-disease risk
  • Shedding body fat
  • Building up muscles and bones
  • Improving memory, mood and vigor
  • Sslowing the aging process

Testosterone makes the man, but a good lifestyle makes him healthy.

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Harvey B. Simon, M.D. is an Associate Professor of Medicine at Harvard Medical School and a member of the Health Sciences Technology Faculty at Massachusetts Institute of Technology. He is the founding editor of the Harvard Men's Health Watch newsletter and author of six consumer health books, including The Harvard Medical School Guide to Men's Health (Simon and Schuster, 2002) and The No Sweat Exercise Plan, Lose Weight, Get Healthy and Live Longer (McGraw-Hill, 2006). Dr. Simon practices at the Massachusetts General Hospital; he received the London Prize for Excellence in Teaching from Harvard and MIT.


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