Similar to what happens to women during menopause, for men over 40, testosterone levels start to fall at an average of about 1.6 percent per year. Once serum testosterone levels fall below normal, symptoms of andropause, including a reduction in vigor and sexual drive, ensue. For young men, testosterone helps build muscles and develop strong bones, boosts energy levels to allow “all-nighters” with ease, and propels foolish actions with the false belief that their youthful bodies can scale an unattainable mountaintop or perhaps leap from a helicopter without a parachute. But during the middle-age years and beyond, that all begins to change, and men in this age group may approach their physicians with concerns about those changes.

As urologists learn more about the role of testosterone in the physical and mental development of young men in their prime, they are also studying the role of testosterone in the aging body. One result of this increased study is that testosterone replacement therapy (TRT) has increasingly been promoted in print media and television, and especially over the Internet, as the solution to the male equivalent of the female menopause, known as andropause. TRT is intended to counter the effects of andropause with promises to improve a man’s libido, increase muscle mass, eliminate cognitive deficiencies, elevate mood, and bolster bone density. Before requesting TRT, however, you need to know what makes a patient a good candidate for this treatment and what the risks and benefits are.


Common Symptoms of Andropause and Hypogonadism

The progressive testosterone (androgen) deficiency that occurs during andropause in aging men can lead to a syndrome known as hypogonadism, which can manifest itself in osteoporosis (loss of bone density), decreased libido, erectile dysfunction, difficulty sleeping, and mood changes (i.e., the “grumpy old man syndrome”). In addition, hypogonadism causes muscle to become flabby and decrease in size, leaving men with the dreaded middle-age paunch. Because serum testosterone levels continue to decline about 1 percent per year, about half of men age 80 and older will have a low serum testosterone and may experience the slow changes to the body listed above.


Who Needs TRT?

Hypogonadism has become widely recognized over the past 10 years. As a result, physicians have increased the number of testosterone replacement prescriptions at an enormous rate. Pharmaceutical studies indicate a 500 percent increase in the use of testosterone products in the elderly and middle-aged population over the last decade, promoting the hopes of turning pot bellies into six-packs, fragile bones into pillars of strength, and grumpy old men into enthusiastic Lotharios.

To determine if you need TRT, your physician will assess your base levels of testosterone. Here are some important numbers to keep in mind: the accepted low limit for normal men is a testosterone level of at least 200 ng/dL (nanograms per deciliter). If a man’s serum testosterone is below 200 ng/dL, TRT may be recommended. If a man’s serum testosterone level falls between 200 and 400 ng/dL, the risk-to-benefit ratio of TRT and its potential hazards, which are discussed below, must be considered. This range of testosterone level is considered a gray zone for TRT. Therefore, a doctor should discuss all the potential risks of TRT with patients whose testosterone levels fall within that zone. For serum testosterone levels of greater that 400 ng/dL, not only is there no benefit for TRT, but there is also considerable risk involved. TRT is absolutely contraindicated in men with normal serum testosterone levels. If testosterone is given in this situation, a patient is no better than a cheating jock attempting to get “juiced” to enhance physical performance. The results can be disastrous.

It is not uncommon to find low serum testosterone in patients with infertility. The testicles are the primary source for the production of testosterone, and the pituitary gland and the brain send signals to the testicles to regulate testosterone production. Low testosterone levels can result from problems either in the pituitary or in the testicles, but in the aging male, the commonest cause is testicular dysfunction. Less common causes for low serum testosterone are testicular injury, undescended testicles, the results of radiation or chemotherapy, and mumps infection affecting the testicles. Other factors resulting in low serum testosterone can include inflammatory disease (such as tuberculosis), HIV and AIDS, opiate use, obesity, and type 2 diabetes.

If a patient displays the commonest side effects associated with low testosterone, usually manifested by a depressed mood, fatigue, anemia, cognitive problems, and hot flashes, a physician may consider the presumptive diagnosis of hypogonadism. The gold standard for diagnostic hypogonadism is to measure the total testosterone levels in the blood to determine if the level is low. Blood is normally drawn for testing in the morning, when testosterone levels are typically the highest.


TRT and Prostate Cancer

Contrary to common thinking, TRT does not cause prostate cancer. However, if a small, undiagnosed prostate cancer is present, TRT can accelerate the growth of the tumor. Older men with high levels of PSA (prostate specific antigen) are not suitable candidates for TRT. Patients receiving testosterone treatment need to have their serum testosterone and overall condition monitored on a regular basis. Patients who respond well to treatment should be monitored every three to four months during the first year of treatment. In men over 50 years of age, a prostate examination (digital rectal exam) and PSA testing every six to twelve months is recommended.


Method of Treatment

Unfortunately, no simple pill exists that can be taken because the oral ingestion of testosterone is extremely toxic to the liver; however, men with confirmed low testosterone levels who choose to undergo treatment have a number of options. Treatment options include injection therapy, wherein testosterone is admitted intramuscularly every two to three weeks. The disadvantage of injections is that they cause a strong surge in the level of serum testosterone shortly after the injection, and this level decreases dramatically by the end of the two- to three-week cycle. The good news is that a number of topical preparations are available. In this method of treatment, the testosterone is applied to the skin and is absorbed into the bloodstream at a constant level. Several gels can be applied to the lower abdomen, upper arm, armpit, or shoulder. As the gel dries, the testosterone is absorbed through the skin. Patients using the gel should not wash the area and should avoid contact with children and female partners for several hours after applying the gel.


Potential Risks Associated with TRT

No discussion of TRT would be complete unless we weighed the risks against the benefits. First, the long-term effects of TRT are not well defined. The main areas of concern are cardiovascular and prostate problems, both of which are common in men with diminished testosterone levels, particularly aging males. Cardiologists have noted that the increased incidence of coronary artery disease in men, compared with women, may be testosterone-dependent. It has been found that aging men receiving long-term TRT have significant changes in their lipid profiles. These changes directly affect cardiovascular health. Unfortunately, TRT lowers the beneficial cholesterol (high-density lipids, or HDL), widely recognized for its role in protecting against coronary artery disease. The good news is that TRT also lowers the bad cholesterol (low-density lipids, or LDL) responsible for blocking coronary arteries. It is encouraging that these effects on the lipid profile may be minimal when TRT maintains a serum testosterone level below 400 ng/dL. However, the cardiac risks increase dramatically when TRT is taken to abusive levels above 400 ng/dL.

Another effect of TRT is increased production of red blood cells. The increase causes a hypercoagulation of the blood, causing a thickening that may increase the potential for a stroke or heart attack. This is especially true in smokers, who already have an increased circulating red blood cell volume. Therefore, physicians should not prescribe TRT that would raise serum testosterone above 400 ng/dL. Having a healthy heart and healthy arteries should not be compromised by the desire to attain a slender waistline or bigger muscles.

A practitioner who starts a patient on TRT should ensure that he does not exceed the recommended dosage in an attempt to radically change his physical appearance. If an aging man longs for that youthful body that is beginning to disappear, a doctor may recommend that he modify his diet, maintain a healthy exercise routine, and accept the realities of aging—a reality that sometimes brings with it a little paunch.

Another important issue to consider surrounding the risks of TRT is its impact on prostate disease. As mentioned previously, it is well known that TRT can cause rapid and potentially catastrophic growth of an unrecognized prostate cancer. There is no evidence that TRT can create prostate cancers; however, if there is even a tiny focus of cancer cells in an otherwise benign prostate, TRT can encourage these cells to grow explosively. This can become life threatening. If a man is receiving TRT, his doctor should be meticulously monitoring his prostate health with semiannual digital rectal examinations (DRE), cancer screening blood tests (PSA), and prostatic ultrasonography.


Prescribing TRT

With the overwhelming media blitz promoting treatment for male andropause and hypogonadism, patients are asking if TRT is safe. Based on the evidence available, it is safe to use TRT, and it is clearly beneficial in symptomatic men with a serum testosterone level of less than 200 ng/dL. (But remember that, in men whose serum testosterone is greater than 400 ng/dL, it is unacceptable.) The results of TRT for symptomatic men are quite remarkable and will improve many of the physical effects associated with the toughest part of life—getting old. TRT is the primary medical treatment available for andropause, and for the right patients, physicians should recommend TRT as appropriate.


A Note on the Placebo Effect

Much of the aging male’s sexuality can be defined as “99 percent between the ears and 1 percent between the legs.” The unscrupulous marketers of non-FDA-approved products and supplements, who often make bold and false claims—that love, sex, size, desire, and performance will be enhanced—rely on the placebo effect. There are many well-controlled scientific studies across the board that show about 40 percent of patients receiving the placebo report that they experience effects similar to those receiving the real product or supplement. Male sexuality, being so intertwined with imagination, mental gymnastics, the power of suggestion, and the illusion of sex appeal, becomes the perfect foil for the wide distribution and enormous profitability of thousands of male “enhancement products” by companies capitalizing on the placebo effect or the power of suggestion.

The takeaway message is this: if you have legitimate symptoms of andropause—weakness, fatigue, loss of libido, increased abdominal girth, mood changes—have your serum testosterone level tested; if it is deficient and you are prescribed an FDA-approved product, see your doctor for regular monitoring.



Photo by Ben White on Unsplash.