26. Testosterone for Life

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26. Testosterone for Life




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Acknowledgments ix

Introduction xiii

Chapter 1

Recognizing the Symptoms 1

Chapter 2

Testosterone and Your Health:

Understanding Testosterone 17

Chapter 3

Could You Have Low Testosterone? 39

Chapter 4

What You Should Know About Being Evaluated

for Low Testosterone 59

Chapter 5

Benefi ts of Testosterone Therapy 79

Chapter 6

Treatment for Low Testosterone Levels 95

Chapter 7

Testosterone and Prostate Cancer 115

Chapter 8

Risks, Side Effects, and Medical Monitoring 141

Chapter 9

Treating Men Who Have a History of

Prostate Cancer 159

Chapter 10

The Future of Testosterone 175

References 183

Index 191

Testosterone for Life

Testosterone is often equated in the popular culture with the macho male physique and virility. Viewed by some as an anti-aging tonic, the growth in testosterone’s reputation and increased use by men of all ages in the United States has outpaced the scientific evidence about its potential benefits and risks. Scientific questions of safety and effectiveness are best answered by randomized clinical trials, the gold standard in clinical research. The Women’s Health Initiative (WHI) and other large-scale clinical trials, for example, have provided new insights into the benefits and risks of postmenopausal hormone therapy in women that are quite different from what had been assumed during decades of widespread use of estrogen-progestin therapy. Now, as large-scale clinical trials of testosterone therapy are being considered by the National Institutes of Health (NIH) and other research organizations, it is important to carefully assess the rationale for such studies so that the research can be designed to best answer questions regarding benefits and risks in a timely and cost-effective manner.

Both men and women are Earthbound, but sometimes it seems they really are from different planets. The biologic model of gender identity attributes the difference to hormones and genes, while the social model examines cultural, educational, and familial influences. In fact, both factors contribute to the behavioral differences, which remain pronounced even as our society becomes more egalitarian.

As a rule, men tend to be less social and more independent, less communicative and more active. Men take more risks and are more aggressive. Men may thank these traits for their political dominance and economic success, but they also contribute to the occupational injuries, accidents, substance abuse, and violence that cost so many men their lives. The problem is particularly acute in young men. Among 15- to 24-year-old Americans, for example, the death rate of males is three times that of females. Motor vehicle accidents and homicides account for much of the difference, but suicide is also more common in teenage boys than girls.
Cultural expectations and peer pressures certainly account for many behavioral differences between the sexes. But hormones also play a role; in particular, testosterone contributes to aggressive behavior, especially in high doses. Neuroscientists are also beginning to assemble data pointing to structural and functional differences in the brains of men and women. For example, scientists in Germany reported that men and women use different parts of their brains to navigate their way out of a maze — and that men are about 28% faster at navigation. It’s an interesting observation, but the researchers didn’t offer any explanation for the legendary male reluctance to ask for directions when their navigational skills fail. Men tend to perform better on certain spatial tasks, but women excel at certain manual tasks requiring precision. Men outperform women on tests of mathematical reasoning, but women do better on arithmetical calculation tests. Males tend to have superior musical and mathematical skills; women, enhanced verbal abilities.

These distinctions, of course, are far from absolute, and it is far from clear if they depend on biology or culture, nature or nurture. Still, new research suggests that testosterone may play an important role in cognitive function.

Testosterone and the mind

All the body’s attributes change with age, and mental function is no exception. Memory is the most fragile mental function. With age, new learning is slower, new information is processed less carefully, and details often slip. Short-term memory typically weakens, but long-term memory is well preserved. These changes give rise to “the senior moment” in healthy elders and to cognitive impairment and dementia in those who are not so lucky.

Testosterone levels decline with age, just when memory begins to slow. Might falling hormone levels account for some of the problem?

Perhaps. The data are far from conclusive, but some studies suggest a link:
• A 2005 study of 565 World War II veterans found that higher testosterone levels in midlife were linked to better preservation of brain tissue in some, but not all, regions of the brain in late life.
• A 2004 study of 400 men age 40 to 80 found that higher testosterone levels were associated with better cognitive performance in older men. No link was observed in younger individuals.
• A 2004 report from the Baltimore Longitudinal Study of Aging evaluated 574 men over a 19-year period. Low free testosterone levels predicted an increased risk of developing Alzheimer’s disease, even after other dementia risk factors were taken into account.
• A 2002 study of 310 men with an average age of 73 found that higher levels of bioavailable testosterone were associated with better scores on three tests of cognitive function.
• A 2002 study of 407 men between the ages of 51 and 91 found that men with higher free testosterone levels achieved higher scores on four cognitive function tests, including visual and verbal memory.
• A 1999 study of 547 men between the ages of 59 and 89 found that high testosterone levels in older men were associated with better performance on several cognitive function tests.

If high testosterone levels are indeed linked to better mental function, will treatments that reduce hormone levels lead to cognitive decline? Androgen deprivation therapy is an effective treatment for advanced prostate cancer and a useful adjunct to radiation therapy for locally advanced prostate cancer. Three studies published in 2005 and 2006 linked androgen deprivation therapy with impaired performance on various cognitive function tests. The effects were modest, however, and certainly should not deter men who need androgen deprivation therapy from receiving it.

Now for the $64,000 question: Can testosterone therapy improve mental function in older men who are healthy or in those with cognitive impairment? Only a few small, short-term studies have examined this question. Subtle improvements on cognitive function tests have been reported, but a 2006 trial found no benefit for healthy older men or Alzheimer’s patients. And in laboratory experiments, high levels of testosterone can trigger apoptosis, the process of cell self-destruction. Until more research is available, men should not use testosterone or any other androgen to improve mental function.

Testosterone and mood

Studies of testosterone and mood are in their infancy. Some research suggests that men with abnormally low testosterone levels, either because of hypogonadism (see below) or androgen deprivation therapy, have an increased incidence of depression, but other studies disagree. Small, short-term studies suggest that testosterone therapy may help alleviate symptoms of depression in some men but that very high doses may promote aggressive or manic behavior. All in all, the bottom line is familiar: More research is needed.

Testosterone therapy

Men who are truly testosterone deficient should receive replacement therapy. The Institute of Medicine estimates that four to five million men are in this category but that only 5% of them are receiving testosterone.

Testosterone deficiency is called hypogonadism. Causes include testicular failure due to genetic errors, mumps, severe trauma, alcoholism, and cancer chemotherapy and radiation. In other cases, the problem originates in the pituitary gland of the brain; causes include tumors (almost all benign), head trauma, brain surgery, various medications, some hereditary disorders, severe malnutrition, and chronic illnesses.
How do doctors diagnose testosterone deficiency? According to the Endocrine Society, men over 50 years of age who have total testosterone levels of 200 ng/dL or lower are hypogonad; they require an evaluation of pituitary function before beginning testosterone therapy. Men with testosterone levels between 200 and 400 ng/dL are borderline and should have additional testing before considering therapy, and men with levels above 400 ng/dL don’t need further tests or therapy.

Until recently, men who needed testosterone required injections of the hormone every one to three weeks. That’s changed dramatically. Now, most men use skin patches (Testoderm, Androderm), gels (AndroGel, Testim), or tablets that are placed on the surface of the gum, where they form a gel that releases the hormone so it can be absorbed across the mouth’s membranes (Striant). All these products require a doctor’s prescription and, except for injections, all are expensive. A safe testosterone pill has not yet been developed.

Testosterone tinkering

If the Institute of Medicine’s estimates are correct, about 250,000 American men are receiving testosterone for hypogonadism, the only condition for which the hormone is approved. 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?
Memory is not the only thing that declines with age. Men also lose muscle mass and bone density; the red blood cell count drifts down; sexual ardor declines; and body fat increases. In theory, at least, testosterone therapy might attenuate or reverse each of these changes.

Unfortunately, doctors don’t know if the theoretical benefits of testosterone can be realized in practice; well-designed, long-term studies have not been performed. And because federal funding agencies think the potential risks of testosterone therapy may outweigh the potential benefits, those studies may be a long time in coming.

The most serious long-term risks of testosterone therapy are prostate diseases, both benign prostatic hyperplasia and prostate cancer. Other potential side effects include polycythemia (an excessive number of red blood cells), sleep apnea (respiratory pauses during sleep that may increase the risk of high blood pressure, heart attack, and stroke), gynecomastia (benign breast enlargement), acne, and liver disease. Cholesterol abnormalities and heart disease were once on that list, but they now appear less likely.
Doctors will have to start at the beginning, with small, short-term trials of testosterone in older men. If the benefits appear to outweigh the risks, the next step will be larger, longer trials in younger men. Only then will men know if testosterone therapy is effective or safe.

It will take time. Meanwhile, men who are really hypogonad should receive testosterone, but other men should not. The experience of millions of American women who took hormone replacement therapy before studies showed that it did more harm than good should help men resist temptation.

But that doesn’t mean you should simply sit back and wait for science to tell you what to do. Keep your mind young and supple with mental activity, physical exercise, good nutrition, and regular medical care. And you can also get many of the purported benefits of testosterone for your body without any of its risks. Along with a healthy amount of dietary protein, resistance exercises and other forms of strength training will help preserve muscle mass and strength, bone density, and musculoskeletal function. A reasonable consumption of calcium (1,200 milligrams a day) and vitamin D (800 international units a day) will help prevent osteoporosis. Above all, perhaps, a program of regular exercise and a low-fat, high-fiber, vegetable- and fruit-rich diet will help prevent atherosclerosis, hypertension, and diabetes — the three major causes of illness, disability, and erectile dysfunction in older men. And since illness and obesity accelerate the age-related decline in testosterone levels, healthy living may actually make your testosterone levels 10 years younger.
It’s never too late to start thinking young and living young — and it’s never too early, either.



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