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Androgens and Androgen Deficiency

courtesy of WebMD
By Christopher Steidle, M.D.

The use of testosterone is widespread. Previous reported uses include infertility, athletic enhancement, erectile dysfunction and libido problems. Their use can have grave consequences if not used prudently. Androgen, or more specifically testosterone, is widely utilized to treat erectile dysfunction. The classic theory about testosterone treatment is that it stimulates the sex drive and, by doing so, restores erectile functioning.

True androgen deficiency is an uncommon diagnosis. Individuals with truly low androgen levels have dramatically augmented their sex drives with the use of testosterone. Because testosterone affects the skin, bone, and skeletal muscle, as well as blood lipids and blood cells, these men generally have muscle weakness, muscle atrophy, little facial and body hair, and a female escutcheon. Depending on what age the deficiency occurred, there may also be changes in the size of the genitalia.

Following a careful history and physical examination, the only accurate way to diagnose the low testosterone state is by measuring the serum level of testosterone. This is a simple blood test that any commercial laboratory can do. At different points during the day, testosterone levels may be widely variable. The human body is cyclical. For example, our state of restfulness or wakefulness varies at different times of the day just as testosterone levels vary.

Serum testing measures testosterone levels in the body. Initially, the hormone that exists in the serum may be bound to a protein that allows it to be transported in the body. This protein is called sex hormone binding globulin (SHBG). The total testosterone consists of two forms of testosterone; one is bound to SHBG and the other is free circulating testosterone unattached to serum proteins. In conditions such as hypothyroidism and cirrhosis, measurement of the total testosterone level may be normal but the patient may have symptoms of low testosterone. In these conditions, the SHBG is increased and this decreases the amount of testosterone that is available for use. The opposite is true where SHBG is decreased and the free testosterone levels are high. This situation is seen in men with obesity and hypothyroidism. These men have normal amounts of testosterone available for use by the body but the serum testosterone level is decreased. Generally, your physician will make the determination of whether to obtain a test measure for both total and free testosterone levels. I usually reserve this in clinical situations where I am suspicious.

Once it has been determined that the testosterone level is low, measuring the luteinizing hormone (LH) can help determine the cause. This separates the patients who have testicular disease from those who have diseases of the pituitary gland, the master gland that sits at the base of the brain and essentially controls many bodily functions. A low testosterone level may indicate an elevated prolactin level as well, a condition known as a hyperprolactinoma. Elevated prolactin can decrease testosterone levels by decreasing the secretion of the hormone that tells the testicle to produce testosterone.

Several things must be weighed before beginning testosterone replacement therapy. In most clinical practice, men are simply given a course of testosterone injections over several months to see if it improves the erectile functioning. This is common in a primary care setting but unfortunately it rarely produces improvement.

Some causes of low testosterone levels include congenital problems (such as deficiencies of male hormones and rare malformation syndromes), and acquired problems, including aging, chronic illness, drugs, starvation, stress, head trauma, infections, cancers, surgeries, alcoholism, removal of or trauma to the testicles, and infection or twisting of the testicles in their sack. This is just a small portion of a long list of possible causes. Another factor is whether or not the testosterone is bound by SHBG. High-fat diets, for example, affect SHBG. Also, certain drugs compete with testosterone in the body, such as spironolactone, an antihypertensive, and danazol, a drug used to treat certain breast conditions in women.

R.Y. was a fifty-one-year-old man who had lethargy and erectile dysfunction. Upon examination he was found to have a normal phallus but very small, firm testicles. He had sparse facial hair and indicated that he shaved only once every week, if even that often. His serum testosterone level was less than 100. His diagnosis was mumps orchitis. He had contracted mumps when he was nineteen, and it had affected both testicles. He was started on testosterone supplementation at a dose of 200 mg every three weeks, which his wife administered. The results were dramatic. He gained weight, began shaving daily, and was able to have sustained intercourse on a regular basis.

Men with low testosterone levels can improve their libido with testosterone treatment. Once a man is diagnosed as hypogonadic, or having a low testosterone level, the next step is to choose which form of treatment to utilize. As with all medications, benefits must be weighed against the numerous risks. Age is one important factor in making this decision. In men less than fifty years old, the goal is to restore libido and erections. Some of the side benefits include preservation of bone mass, much in the same way estrogen helps prevent osteoporosis in menopausal women. Testosterone also improves strength, physical stamina, and general well-being. It almost sounds like this is the perfect drug.

The downside of testosterone is that it can increase serum cholesterol. It can also increase the growth of the prostate, and if early-stage prostate cancer is present, treatment may stimulate wild growth. The analogy I use with patients is that testosterone treatment is like throwing Miracle Grow on a patch of weeds. So it is extremely important to be sure you don't have prostate cancer before beginning testosterone replacement therapy.

Testosterone preparations are as numerous as the causes for low testosterone. Physicians have a host of choices, including oral or sublingual preparations, patches, pellets, and shots. In the injectable category there are numerous short-acting and long-acting preparations. We will briefly discuss each of the preparations and the risks and benefits of each.

Before beginning testosterone replacement therapy, I also recommend monitoring prostate-specific antigen (PSA) levels. The PSA is a useful marker that aids in the diagnosis and management of prostate cancer. It is extremely important to know the baseline PSA before beginning therapy. I also check baseline liver function to be sure that there is no liver damage prior to testosterone therapy, and finally, I do a baseline blood lipid test. I then monitor the blood lipids at least twice a year. I carefully counsel the patient about the potential downfall of this type of therapy since long-term testosterone therapy has been associated with prostate cancer. Men who have low levels of testosterone are still at risk for prostate cancer.

Oral Preparations

The major drawback to oral preparations of testosterone is the fact that they must be in a form that will allow their absorption from the GI tract. In other words, they are taken by mouth as an inactive form, absorbed, and then activated in the liver, a process known as methylation. Unfortunately, this is not an ideal situation as these preparations are fraught with liver dysfunction. Additionally, the half-life of these preparations is very short, and they must be taken throughout the day.

The oral preparations available in the United States are perhaps the least desirable way to replace testosterone, and I personally feel that there are no indications to use these in replacement therapy. Other oral preparations available outside the United States are reported to be somewhat better. They are compounded with medications that allow the testosterone to bypass the liver and avoid liver toxicity. Unfortunately, these are not currently available in the United States.

Transdermal Preparations

Two transdermal preparations are widely available. The first and original is a patch worn on the scrotum. The scrotal skin is ideal, not because of its position but because of its unique properties that allow the testosterone to absorb into the skin. The scrotal skin is thinner and has a higher circulation than other skin surfaces. This type of treatment has a low incidence of side effects, but the major drawback is the need to shave the scrotum on a fairly regular basis and to use a hairdryer to apply it. This preparation, unfortunately, has not become extremely popular.

Recently, another testosterone replacement preparation has been approved that uses the unique delivery system of daily placing the patch on the torso. With this method, serum testosterone levels remain stable, unlike the wide swings of the injection method, and patients can thereby avoid the monthly injections. Downsides, however, include skin lesions and dermatitis, and it is expensive. Common skin rashes can be avoided by pretreatment with cortisone creams. Also, many patients who prefer the transdermal route have third party insurance plans that pay for prescription medications because the cost is prohibitive for men who are on chronic replacement therapy.

R.B. was a fifty-one-year-old executive. He had a sudden loss of interest in sexual relations. A careful history revealed that he was able to achieve an erection but had no desire in having intercourse. He had recently remarried, and the relationship had initially been extremely physical. His testosterone level was extremely low, and further evaluation indicated a high serum prolactin level. He indicated that he also had double vision and headaches as well. His diagnosis was a prolactinoma; a small prolactin-secreting tumor at the base of the brain in the area known as the pituitary. Treatment with the drug bromocriptine was dramatic and has totally resolved the problem.

Both preparations are widely available, and it is certainly important to discuss these options with your physician when considering testosterone replacement therapy.


Currently, the most popular method of testosterone supplementation is by injection. The most common compound and the ones used for decades in the United States are testosterone cypionate and testosterone enanthate. These are generally given as a 200-mg injection every two to three weeks. Results are usually satisfactory for the majority of patients.

The downside to this has been an initial super-physiologic testosterone level during the first few days after the injection followed by a decrease. In other words, when you first get the injection, the testosterone level goes much higher than natural levels would be, and then tends to drop. This creates a peak-and-valley situation. It is usually not noticeable to patients. Some physicians, however, feel that the intermittent elevations may have more long-term consequences than a steady level produced by transdermal preparations.

Studies are currently investigating whether transdermal testosterone has advantages over testosterone shots. Again, this is not a clear situation, and so it is important to discuss this with your physician. In my clinical practice, most patients choose testosterone injections because of cost considerations. I generally teach patients or their partners how to give the injection, and then prescribe the appropriate dosages. Cost is roughly $10 for a 10-cc vial, which is good for up to fifteen weeks. It is the most cost-effective option available.

Other types of testosterone preparations include testosterone pellets that can be implanted much the same as the Norplant, although this is not available worldwide. Studies are also looking at testosterone given under the tongue, or sublingually. The most important take-home message in this situation is that each testosterone delivery system has its benefits and side effects. It is important that both patient and physician understand them thoroughly.

The current recommendation for men about to undergo testosterone replacement therapy is either the transdermal or transcrotal patch or testosterone cypionate injections, 200 mg every two weeks, or 400 mg every month. The downside to the 400 mg dose is that the peak-and-valley effect is more dramatic than with the 200-mg treatments. Men on 400 mg should be carefully watched for signs of liver toxicity as well as changes in the blood lipids.



Copyright 1998 NTC/Contemporary Publishing Group. From The Impotence Sourcebook, by arrangement with The RGA Publishing Group. The Impotence Sourcebook

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