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Science/Tech
See other Science/Tech Articles

Title: Testosterone replacement: A cautionary tale
Source: [None]
URL Source: [None]
Published: Oct 26, 2011
Author: staff
Post Date: 2011-10-26 00:32:46 by Tatarewicz
Keywords: None
Views: 81
Comments: 1

"Every man desires to live long," wrote Jonathan Swift, "but no man would be old." Much has changed over the centuries, but the desire to retain youthful vigor during the golden years has endured. Fortunately, modern medicine has developed a plan for successful aging. It includes getting regular physical activity and mental stimulation; eating right; controlling blood pressure, cholesterol, and blood sugar levels; staying lean; building strong interpersonal relationships; and avoiding tobacco and other risky exposures and activities.

A wise lifestyle can help extend life and slow the aging process - but it takes effort and discipline, especially for gents who have started down the wrong path. So it's no surprise that men continue to look for a medicinal shortcut. One of the most tempting is testosterone.

The manly hormone

Testosterone is the most powerful androgen, a group of steroid hormones whose name is derived from the Greek words for "man-maker." The name is appropriate, since androgens are responsible for the large muscles, strong bones, deep voice, and pattern of hair growth that characterize the gender. The hormone promotes the production of red blood cells. Testosterone also stimulates the growth of the genitals at puberty, and it's responsible for sperm production throughout life. In addition, it has major, if incompletely understood, effects on male behavior; testosterone contributes to energy (and aggressiveness), is essential for the sex drive, and plays a role in normal erections and sexual performance. And after the hormone is converted to dihydrotestosterone, it stimulates the growth of prostate cells and stuns the hair follicles of men genetically predisposed to male pattern baldness.

Testosterone and aging

As men age, things change. Bone calcium declines, muscle mass decreases, and body fat increases. Red blood cell counts decline. The average man becomes less energetic and less sexually active.

As all this occurs, testosterone levels are falling. Total testosterone levels fall by about 1% a year starting around age 40, while bioavailable testosterone, the form that does the hormone's work, falls about 2% a year.

Putting declining testosterone levels and diminishing male capacities together, it's easy to see why testosterone therapy is so appealing. Remember, though, that despite slowly falling hormone levels, most men stay in the normal range throughout life. In addition, although hormone levels wane as men age, there is no proof that falling levels cause the undesirable effects of aging, or that testosterone therapy will reverse those changes. Finally, and most importantly, many doctors are worried that testosterone therapy may not be safe. They remember that, in women, major studies turned conventional wisdom on its ear by reporting that postmenopausal hormone replacement therapy does more harm (breast cancer, heart attacks, and strokes) than good, particularly for older women.

The safety of testosterone therapy for older men remains controversial. Its role in prostate disease, both benign prostatic hyperplasia (BPH) and prostate cancer, is one unresolved issue. Other possible side effects include polycythemia (an excessive number of red blood cells), sleep apnea (respiratory pauses during sleep that can increase the risk of hypertension, heart attack, and stroke), gynecomastia (benign breast enlargement), acne, and liver disease.

More research is needed to learn if these concerns about the safety of testosterone are justified. But doctors were close to crossing heart disease off the testosterone worry list, since studies seemed to exonerate it as a cardiac risk. Unfortunately, though, one study will reignite debate about testosterone and heart disease.

Symptoms of testosterone deficiency

Highly suggestive

* Decreased sex drive (libido) and sexual activity * Decreased spontaneous erections * Shrinking or very small testicles * Reduced facial or body hair * Osteoporosis, low-trauma fracture, loss of height * Breast enlargement or discomfort * Hot flashes and night sweats * Infertility

Less specific symptoms

* Loss of muscle bulk or strength * Decreased energy, fatigue, or lethargy * Increasing body fat * Depression * Poor concentration and memory * Disturbed sleep or increased sleepiness * Anemia * Diminished physical function

The TOM trial

The Testosterone in Older Men with Mobility Limitations (TOM) trial was designed to evaluate the efficacy and safety of testosterone therapy in men who seemed to need the hormone most. All of the participants were 65 years of age or older, had low or low-normal testosterone levels, and had limited ability to walk or climb stairs, which suggested muscular weakness. On average, the men were overweight, and the majority had hypertension. But the study excluded men at high risk of complications. All the participants had normal prostate specific antigen (PSA) levels, none had severe lower urinary tract symptoms, and none had been diagnosed with prostate cancer or other active malignancies. In addition, none of the men had uncontrolled hypertension, unstable angina or a recent heart attack, advanced heart failure, poorly controlled diabetes, abnormally high red blood cell counts, or severe sleep apnea, and only 9% were current smokers.

The volunteers were randomly assigned to receive daily treatment with a standard testosterone gel or a placebo gel. As expected, blood testosterone levels rose only in the treatment group, but never to abnormally high levels. Muscular strength and red blood cell counts improved significantly in the testosterone-treated men. Blood pressure did not change; the hormone produced a fall in HDL ("good") cholesterol levels, but LDL ("bad") cholesterol also fell.

The TOM study plan called for 252 participants and six months of therapy. But the study's data and safety monitoring board halted it after just 209 men were enrolled, of whom 129 had completed six months and 47 had completed 12 or more weeks of therapy. The reason was an excess of cardiovascular events in the men who received testosterone. In all, cardiovascular events developed in 23 of the 106 men who received testosterone, compared with five cardiovascular events in the 103 men who received placebo. The increase in cardiovascular complications associated with therapy remained significant even after the researchers took underlying risk factors into account. The testosterone-treated men also experienced a higher rate of complications involving the respiratory tract and skin.

Perspectives

The TOM study raises a red flag about testosterone therapy in older men, but it does not merit a stop sign. The study was designed primarily to evaluate muscular strength, not cardiac effects, so the cardiovascular side effects were less closely monitored than they might otherwise have been. The heart problems included a range of difficulties, rather than just one specific hazard. The testosterone therapy began at 100 milligrams (mg) a day, while the manufacturer's recommended starting dose is 50 mg a day, with an option to increase to 100 mg after two weeks. Finally, the study was relatively small and brief and the participants were older men (average age 74) with a high prevalence of cardiovascular risk factors, such as hypertension, obesity, and abnormal cholesterol levels.

Despite these mitigating factors, the TOM study is cause for concern. Many of the studies that report that testosterone is safe for the heart are substantially smaller and briefer than TOM. Some of the earlier studies used lower doses of testosterone but others used similar doses, and the TOM scientists adjusted the dosage to keep blood testosterone levels in the desired physiological range. The men who participated in TOM were older, less mobile, and more likely to have cardiovascular risk factors than the men in some other trials, but they are also the very type of men who might be most likely to benefit from hormone therapy.

Who should take testosterone?

Testosterone replacement therapy is approved for men with testosterone deficiency, or 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.

Nearly all men with hypogonadism have total testosterone levels below 300 nanograms per deciliter (ng/dL), free testosterone levels below 5 ng/dL, and bioavailable testosterone levels below 150 ng/dL. But since hormone levels fluctuate widely during the course of the day, blood should be drawn between 7 a.m. and 10 a.m. for greatest accuracy. And although testing is relatively simple, most experts recommend that it be reserved for men with symptoms that suggest hypogonadism (see "Symptoms of testosterone deficiency").

Men with hypogonadism should receive testosterone replacement therapy. Exceptions include patients who have had prostate or breast cancer, unexplained high PSA levels, prostate nodules or severe BPH, elevated red blood cell counts or abnormally viscous ("thick") blood, untreated obstructive sleep apnea, or severe heart failure. And the TOM study suggests that older men and those with cardiovascular disease or major risk factors should receive testosterone with extreme care, if at all.

According to the Institute of Medicine, 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.

Most of these men are taking testosterone for its purported "anti-aging" effects or for erectile dysfunction (with benefit very doubtful). Even without considering possible prostate problems, the TOM study reminds us that taking testosterone is serious business, with potential hazards. Many experts believe that testosterone therapy should be restricted to men with hypogonadism or to those enrolled in careful clinical trials. Unbiased research is the only way to learn if testosterone therapy is a boon or bane.

Harvard Men's Health Watch

Volume 15 - Number 7

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#1. To: Tatarewicz (#0)

You can increase testosterone naturally by working out.

God is always good!

RickyJ  posted on  2011-10-26   3:00:48 ET  Reply   Trace   Private Reply  


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