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To T or Not to T: Is That the Question?

More than half of all men who reach 80 are clinically deficient in testosterone. Coincidentally, that’s the primary age at which prostate cancer manifests.

“I don’t believe in andropause.” With those words, John’s doctor summarily dismissed John’s request for testosterone-replacement therapy (TRT). The word andropause refers to a drop in the primary male hormone, testosterone, as part of the aging process. Along with the drop in testosterone, which occurs at a rate of 1 to 2 percent per year, commencing at around age 40, comes a host of symptoms.

John based his request on a recent blood test, which showed a 316 testosterone level. While some doctors consider that a “low normal” level, it wasn’t from John’s point of view. The normal level of testosterone ranges from 300 to 1,000 nanograms per deciliter of blood, with younger men having higher levels. Since John was a lifelong bodybuilder, his low testosterone levels likely had something to do with his lack of gains in muscle size and strength in recent years.

John’s doctor warned him that using any form of testosterone was a “known stimulant of prostate cancer, as well as cardiovascular disease.” The doctor was echoing the opinion of many physicians. In their collective minds, male menopause, another term for andropause, just didn’t exist. Yet many of those same doctors still provided hormonal-replacement therapy (HRT) in the form of estrogens and progestins to women, ostensibly because of the established health benefits.

Many in the medical profession think that a gradual lowering of testosterone in men is simply an inevitable part of the aging process. Their concerns about the alleged dangers of TRT are usually based more on emotion than on science, such as the notion that TRT causes prostate cancer and promotes cardiovascular disease.

Another reason, of course, is the steroid stigma. While anabolic steroids, which are altered versions of testosterone, do have some valid medical uses, the negative publicity about rampant steroid abuse in sports has led many to conclude that the negatives outweigh any positives. Government pressure on physicians to avoid dispensing testosterone-related drugs also plays a role here.

Testosterone Deficiency: Real or Imagined?

Despite the continuing skepticism of many in the medical profession, the TRT prescription rate continues to rise. Studies show a 500 percent increase in the sale of testosterone-based drugs between 1993 and 2001, and that rate continues to grow. Numerous studies dispute the previously held dogma that TRT is dangerous to long-term health. Along with that, men are refusing to go gently into that good night, refusing to accept feebleness and lack of quality of life simply because their bodies are no longer making optimal amounts of a hormone that has flowed in their blood since birth.

When a man reaches middle age, an event occurs in his body that turns off testosterone. The event may initially occur in the brain, through a gradually diminished secretion of the gonadatropins that govern the release of luteinizing hormone, a pituitary gland agent that controls the synthesis of testosterone in the testes. Or it could happen in the testes themselves. In that case the testicular cells refuse to respond to LH’s prodding signal to kick up testosterone production.

A less commonly discussed cause of lower testosterone levels in men, particularly middle-aged men, is a gradual increase in bodyfat. Deep-lying fat in the abdomen, known as visceral fat, is linked to both insulin resistance and lower testosterone levels. Higher levels of belly fat lead to lower levels of sex-hormone-binding globulin, the protein-binding hormone of testosterone, in the blood. That, in turn, makes free testosterone circulating in the blood more susceptible to the actions of aromatase, an enzyme found in fat and other tissues that converts testosterone into estrogen. The increase in estrogen signals the hypothalamus in the brain to curtail the release of gonadotrophic hormones that dictate testosterone synthesis. The lack of testosterone leads to even greater fat deposition in the abdomen and under the skin, producing a vicious metabolic cycle that results in lower testosterone levels, along with a heightened risk of diabetes, high blood pressure, cardiovascular disease and the metabolic syndrome.1

Various published studies show a close relationship between testosterone levels and the onset of various degenerative diseases. Much of that relates to the link between testosterone and bodyfat. In short, an optimal level of testosterone promotes fat loss, with the converse also being true: A lack of testosterone promotes bodyfat gain. In a recent study that examined the connection between sex hormones and type 2 diabetes, a higher testosterone level led to a 42 percent lower risk of type 2 diabetes in men, although higher levels of the hormone appeared to increase the risk in women.2 Men who had diabetes also showed higher estrogen levels than men who didn’t have it.

More than half of all men who reach 80 are clinically deficient in testosterone. Coincidentally, that’s the primary age at which prostate cancer manifests. Thus the men lowest in testosterone experience the highest incidence of prostate cancer.

ALLJust what does having deficient testosterone levels do to a man? Among the effects of low testosterone:3

•Mental depression
•Lowered bone density, predisposing to fractures
•Decreased energy, vitality and sense of well-being
•Lowered muscle mass and strength
•Impaired cognition, or brain function
•Increased fatigue
•Sexual problems, including lowered sex drive, impotence, difficulty achieving orgasm, decreased orgasm intensity (gasp!), decreased penile sensation

Despite the plethora of symptoms, only 5 percent of affected men receive TRT. Yet replacement doses reverse all of the above symptoms. For example, TRT increases libido, as well as sexual function. Providing TRT always has beneficial effects on body composition, including added muscle mass and strength, as well as a selective loss of bodyfat, particularly in the abdomen.

Some studies suggest that a lack of testosterone may be related to mental degeneration in men, including Alzheimer’s disease.4

Are the Risks Real?

But what about the claims that testosterone-replacement therapy is risky because it may be related to prostate cancer and cardiovascular disease? First, consider the goal of TRT. The primary goal is to provide a replacement dose of testosterone, just enough to bring a low level to a mid-normal level. In that sense, TRT isn’t much different from taking vitamin and mineral supplements to replace the nutrients that you aren’t getting through your diet. The confusion about the alleged dangers of TRT arises because people assume that its goal is to provide superphysiological, or above normal, levels of testosterone. That’s what occurs with athletic use of anabolic steroids, with athletes often taking several such drugs concurrently, or stacking them. The resulting levels of testosterone in the blood far exceed what could occur naturally. They have nothing to do with supplemental replacement doses of testosterone.

That’s not to say that no side effects are possible. For example, testosterone increases the rate of red blood cell production, stimulating a kidney hormone called EPO. For many older men that’s considered beneficial, because some older men are anemic. In fact, oral steroid drugs, such as Anadrol, were used early on to treat certain forms of hereditary anemia. That role of steroids has been supplanted by recombinant EPO drugs, which are also abused in sports. About half of the men who inject testosterone drugs have red blood cell counts that are too high, leading to increased viscosity of the blood. That, in turn, increases the chance of a blood clot or stroke occurring in predisposed men. This particular side effect doesn’t occur with other forms of TRT, such as patches. Another thing to consider is that most men who are deficient in testosterone are also anemic, according to a recent study.2

About 2 percent of men undergoing testosterone-replacement therapy may experience other symptoms, including gynecomastia, or male breast tissue formation. This occurs when testosterone is converted to estrogen by way of the ubiquitous aromatase enzyme. Bodybuilders and other athletes deal with the problem by using various anti-aromatase drugs, such as Arimidex, that effectively curtail the conversion of testosterone into estrogen. That, however, could be a problem for men undergoing TRT because the conversion of a portion of the testosterone that’s converted to estrogen helps to maintain levels of high-density lipoprotein, the so-called good cholesterol, which offers potent cardiovascular-protective benefits.

Other men occasionally experience peripheral edema, or water retention in the arms and legs. Those with sleep apnea can experience worse sleep problems with testosterone-replacement. The same can occur with those who tend to get acne. Younger men who use TRT may note a shrinkage of the testes, as well as decreased fertility. Transdermal testosterone drugs are associated with localized skin reactions in 3 to 5 percent of users, while patches produce irritation in 40 percent of users. Those who eschew injections or skin patches or creams and opt for oral versions of testosterone risk increased liver abnormalities.

An observation some 60 years ago that removing the testes seemed to control or prevent prostate cancer led to the prevailing notion that testosterone causes prostate cancer. In men with prostate cancer, administering testosterone may indeed speed the growth of a tumor, but there’s no evidence that testosterone itself is a carcinogen. Some men who undergo TRT may have an increase in prostate gland volume during the first six months of therapy, but that doesn’t often cause problems.

Some scientists suggest that all men harbor small focuses of localized cancers in their prostate gland, and using testosterone may “turn on” one of those dormant tumors, turning it into full-blown prostate cancer. Nevertheless, studies show that the risk of prostate cancer in men undergoing TRT is less than 1 percent, or about the same as men not receiving any type of TRT. Other studies show that men who have higher levels of testosterone are not more prone to getting prostate cancer, nor are men with lower testosterone less prone to getting it. Even men with a higher risk of prostate cancer show no increased incidence while undergoing TRT.6

Next month I’ll cover the cardiovascular effects of testosterone-replacement and the forms of such therapy that are available.


1 Cohen, P.G. (2001). Aromatase, adiposity, aging, and disease. The hypogonadal-metabolic-atherogenic-disease and aging connection. Med Hypotheses. 56:702-708.

2 Ding, E.L., et al. (2006). Sex differences of endogenous sex hormones and risk of type 2 diabetes. JAMA. 295:1288-1299.

3 Rhoden, E., et al. (2004). Risks of testosterone-replacement therapy and recommendations for monitoring. N Eng J Med. 350:482-92.

4 Cherrier, M.M., et al. (2001). Testosterone supplementation improves spatial and verbal memory in healthy older men. Neurology. 57:80-88.

5 Ferrucci, L., et al. (2006). Low testosterone levels and the risk of anemia in older men and women. Arch Intern Med. 166:1380-1388.

6 Rhoden, E., et al. (2003). Testosterone-replacement therapy in hypogonadal men at high risk for prostate cancer: Results of one year of treatment in men with prostatic intraepithelial neoplasia. J Urol. 170:2348-51. IM

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