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.
Injections
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.
