Testosterone is the silver bullet for restoring youth in men once testosterone deficiency starts becoming apparent. Blood testosterone levels naturally peak in young men around age 18 and continue to stay elevated in the second decade of life, but start to gradually decline around age 30. This age-related gradual decline eventually leads to profound testosterone deficiency in men around age 40.
Most men begin to have minor signs and symptoms such as fatigue and weight gain in their 30’s, but the symptoms are usually non-specific and not profound enough to seek the help of a physician specialized in hormone therapy. For those individuals who visit a primary care physician for a full work-up, an annual physical exam does not generally include a full hormonal work-up and testosterone deficiency can be missed. Even if testosterone levels are checked, some physicians check total testosterone levels instead of a full panel which includes total testosterone, free testosterone, and SHBG (sex hormone binding globulin).
Recently, I had a 50 year old patient who complained of weight gain in the abdominal region despite regular exercise and a healthy diet. He complained that his waist seems to be getting larger despite all efforts at the GYM and a healthy diet that has not changed in years. He mentioned his total weight on the scale has remained about the same, but his abdominal girth is larger and he has significantly less muscle mass in his arms and shoulders. He is a busy executive with a family and 2 teenage children, but his stress level has not particularly changed at the office or at home. He has noticed however, that he drinks more coffee to sustain energy at work, and has to drink energy drinks while driving long distances to stay awake, and his libido has decreased. When I inquired about his last check-up, he proudly pulled out several pages of labs which he had proactively requested from his primary care physician for our visit. Not to my surprise, a full age-related panel was done delineating normal cholesterol, prostate antigen, sugar, liver, kidney, blood count, and total testosterone levels. The total testosterone level was 375 ng/dl and of course within the reference range. This case brings up several important points:
- Given normal total testosterone levels (within reference range), does this patient have testosterone deficiency to explain the symptoms?
- Are there any other testosterone related tests that could be important in evaluating this patient?
- Should he be treated based on symptoms alone despite a normal reference range?
- What about the risks and the benefits of treatment?
- Given different available testosterone formulations (injections, patch, gel, cream), which type of therapy should one choose?
In males, testosterone is made in the testicle and released into the blood where it binds a protein called albumin, and another protein called Sex Hormone Binding Globulin (SHBG). Free testosterone which is the active testosterone is actually the smallest percentage of bioavailable hormone, which is not protein bound and ready for uptake into any cell or tissue such as the muscle.
Checking total testosterone levels without checking free testosterone levels could give a false impression that levels are normal when in fact could be severely low. The levels of SHBG are inversely proportional to free testosterone levels, therefore the levels tend to rise with age where total and free testosterone levels decline with age.
So what is the definition of low testosterone and should levels be compared to one’s age or clinical symptoms?
Low testosterone therapy is the treatment of low levels of testosterone, or any level of testosterone that is associated with symptoms such as low sex drive, erectile dysfunction, loss of lean body mass or muscle atrophy, fatigue, depression, osteoporosis, osteopenia, and increase in body fat percentage.
Normal aging is associated with primary hypogonadism or low testosterone. Conventional medicine defines low testosterone as levels lower <320 ng/dL and low free testosterone <64 pg/mL.
Here is the problem with conventional medicine and the above definition: Many physicians focus on “normal levels” or levels that are above 320 ng/dL and ignore symptoms of low testosterone such as fatigue, depression, muscle atrophy, erectile dysfunction, low sex drive, and weight gain. If and when the levels fall in the normal range, testosterone therapy is rarely offered to the patient.
In the case of my 50 year old patient with total testosterone level of 375 ng/dl, which is actually within a normal range, free testosterone was checked and turned out to be low, and SHBG was high, which means the testosterone was not bioavailable in the first place and bound to SHBG. This patient’s clinical symptoms were related to testosterone deficiency and he improved significantly with treatment.
Possible risk factors:
Low testosterone therapy has been somewhat controversial among some doctors due to potential adverse effects of testosterone replacement therapy, but most studies have demonstrated treatment benefits. It is important to note that when testosterone therapy is done scientifically and systematically, in the hands of an expert physician focused on hormone replacement therapy, there should be no side-effects related to testosterone replacement therapy. In fact, the only side-effect would be the promotion of good health, cardiovascular benefits, and rejuvenation. Those individuals who are treated incorrectly, can experience prostate enlargement, hair loss, acne, and possibly cardiovascular events.
For example, if a large bolus of testosterone is injected bi-monthly, the body converts a portion of that exogenous testosterone to a hormone called estradiol, which causes gynecomastia (enlargement of breast tissue), flushing, sweating, and weight gain. Unfortunately, most centers treat low testosterone with large boluses of testosterone and fail to follow the natural biological rhythmic testosterone production, which causes an abnormal biological hormonal balance.
Besides converting to estrodiol, testosterone can also convert to another hormone known as DHT which causes hair loss, male pattern baldness, and prostate enlargement. If testosterone therapy is dosed incorrectly, and the wrong testosterone formulation is used, hair loss could indeed be a side-effect of therapy.
Most importantly I would like to emphasize there is no evidence that low testosterone therapy could lead to cancer of the prostate.
There are several different formulations of testosterone that could be used including testosterone gel, testosterone topical solution, testosterone patch, testosterone cypionate, testosterone pellets, and buccal testosterone. Generally speaking, the type of testosterone formulation is decided based on the physician’s experience with certain formulations and the patient’s preference, cost, and therapeutic goals.
Generally speaking, I would recommend avoiding topical forms of testosterone such as patches, gels, and other formulations that enter through the skin, simply because topical formulations promote conversion of testosterone to DHT which is the hormone responsible for causing hair loss and prostate enlargement. Skin reactions are common when using the transdermal patch, but the injections are very well tolerated. In young boys, rapid increase in testosterone after treatment may lead to psychological difficulties and aggressive behavior, in particular when abused without a prescription and not carefully monitored.
In conclusion, low testosterone therapy in men should be considered when levels are low and associated with symptoms such as lack of libido, erectile dysfunction, depression, osteoporosis, and muscle atrophy.
Although side-effects are rare when therapy is done by an expert physician focused on low testosterone therapy, gynecomastastia (enlargement of breast tissue), hair loss, prostate enlargement, and acne are among potential side-effects, in particular if therapy is not carefully dosed and not monitored by highly trained individuals.