A Harvard Specialist shares his Ideas on testosterone-replacement therapy
An interview with Abraham Morgentaler, M.D.
It might be said that testosterone is the thing that makes men, guys. It gives them their characteristic deep voices, large muscles, and body and facial hair, distinguishing them from girls. It stimulates the growth of the genitals at puberty, plays a role in sperm production, fuels libido, and leads to normal erections. Additionally, it boosts the production of red blood cells, boosts mood, and assists cognition.
Over time, the "machinery" which makes testosterone gradually becomes less powerful, and testosterone levels start to drop, by approximately 1% per year, beginning in the 40s. As men get in their 50s, 60s, and beyond, they may begin to have symptoms and signs of low testosterone such as reduced sex drive and sense of vitality, erectile dysfunction, diminished energy, reduced muscle mass and bone density, and anemia. Taken together, these symptoms and signs are often called hypogonadism ("hypo" meaning low working and"gonadism" referring to the testicles). Researchers estimate that the illness affects anywhere from two to six million men in the USA. Yet it is an underdiagnosed problem, with just about 5 percent of those affected undergoing therapy.
Various studies have shown that testosterone-replacement therapy may provide a wide range of advantages for men with hypogonadism, such as enhanced libido, mood, cognition, muscle mass, bone density, and red blood cell production. Much of the current debate focuses on the long-held belief that testosterone may stimulate prostate cancer.
Dr. Abraham Morgentaler, an associate professor of surgery at Harvard Medical School and the director of Men's Health Boston, specializes in treating prostate diseases and male reproductive and sexual difficulties. He has developed specific experience in treating lower testosterone levels. In this interview, Dr. Morgentaler shares his views on current controversies, the treatment strategies he uses with his patients, and why he thinks specialists should rethink the potential link between testosterone-replacement therapy and prostate cancer.
Symptoms and diagnosisWhat symptoms and signs of low testosterone prompt that the typical man to see a doctor?
As a urologist, I tend to observe guys since they have sexual complaints. The main hallmark of low testosterone is low sexual desire or libido, but another can be erectile dysfunction, and any man who complains of erectile dysfunction must possess his testosterone level checked. Men can experience other symptoms, such as more difficulty achieving an orgasm, less-intense orgasms, a much lesser quantity of fluid out of ejaculation, and a feeling of numbness in the penis when they see or experience something that would usually be arousing.
The more of these symptoms there are, the more likely it is that a man has low testosterone. Many physicians tend to dismiss these"soft symptoms" as a normal part of aging, but they are often treatable and reversible by normalizing testosterone levels.
Aren't those the same symptoms that guys have when they're treated for benign prostatic hyperplasia, or BPH?
Not exactly. There are a number of drugs which may reduce libido, such as the BPH medication finasteride (Proscar) and dutasteride (Avodart). Those drugs may also reduce the quantity of the ejaculatory fluid, no wonder. But a reduction in orgasm intensity usually does not go along with treatment for BPH. Erectile dysfunction does not usually go along with it either, though surely if a person has less sex drive or less interest, it is more of a struggle to have a fantastic erection.
How can you determine whether a man is a candidate for testosterone-replacement therapy?
There are two ways we determine whether somebody has low testosterone. One is a blood test and the other is by characteristic signs and symptoms, and the correlation between these two approaches is far from perfect. Generally guys with the lowest testosterone have the most symptoms and guys with maximum testosterone have the least. But there are a number of guys who have low levels of testosterone in their blood and have no symptoms.
Looking at the biochemical numbers, The Endocrine Society* believes low testosterone for a entire testosterone level of less than 300 ng/dl, and I think that's a sensible guide. However, no one quite agrees on a few. It is not like diabetes, where if your fasting sugar is over a certain level, they'll say,"Okay, you've got it." With testosterone, that break point is not quite as apparent.
| *Note: The Endocrine Society publishes clinical practice guidelines with recommendations for who should and shouldn't receive testosterone check my reference treatment. For a complete copy of the guidelines, log on to www.endo-society.org. |
Is complete testosterone the right point to be measuring? Or if we are measuring something else?
Well, this is just another area of confusion and good debate, but I do not think that it's as confusing as it appears to be from the literature. When most physicians learned about testosterone in medical school, they heard about total testosterone, or all of the testosterone in the body. But about half of the testosterone that's circulating in the bloodstream is not readily available to the cells. It's closely bound to a carrier molecule called sex hormone--binding globulin, which we abbreviate as SHBG.
The available portion of total testosterone is known as free testosterone, and it's readily available to cells. Almost every laboratory has a blood test to measure free testosterone. Even though it's just a small portion of the overall, the free testosterone level is a fairly good indicator of low testosterone. It is not perfect, but the correlation is greater compared to total testosterone.
This professional organization recommends testosterone treatment for men who have both
- Reduced levels of testosterone in the blood (less than 300 ng/dl)
- symptoms of low testosterone.
Therapy is not Suggested for men who have
- Breast or prostate cancer
- a nodule on the prostate which can be felt during a DRE
- that a PSA greater than 3 ng/ml without additional evaluation
- a hematocrit greater than 50% or thick, viscous blood
- untreated obstructive sleep apnea
- severe lower urinary tract infections
- class III or IV heart failure.
Do time daily, diet, or other factors affect testosterone levels?
For many years, the recommendation has been to receive a testosterone value early in the morning since levels start to fall after 10 or 11 a.m.. But the information behind that recommendation were attracted to healthy young men. Two recent studies demonstrated little change in blood testosterone levels in men 40 and mature within the course of the day. One reported no change in typical testosterone till after 2 p.m. Between 2 and 6 p.m., it went down by 13 percent, a small amount, and probably insufficient to influence identification. Most guidelines nevertheless say it's important to perform the evaluation in the morning, but for men 40 and over, it likely doesn't matter much, as long as they obtain their blood drawn before 5 or 6 p.m.
There are a number of rather interesting findings about diet. By way of example, it appears that those who have a diet low in protein have lower testosterone levels than men who eat more protein. But diet has not been studied thoroughly enough to make any recommendations that are clear.
Exogenous vs. endogenous testosteroneWithin this article, testosterone-replacement treatment refers to the treatment of hypogonadism with exogenous testosterone -- testosterone that is produced outside the body. Based on the formulation, treatment can lead to skin irritation, breast tenderness and enlargement, sleep apnea, acne, reduced sperm count, increased red blood cell count, and other side effects. In a recent prospective study, 36 hypogonadal men took a daily dose of clomiphene citrate for three or more months. Within four to six months, all of the men had heightened levels of testosterone; none reported some side effects throughout the entire year they had been followed. Because clomiphene citrate is not approved by the FDA for use in men, little information exists regarding the long-term ramifications of carrying it (such as the probability of developing prostate cancer) or if it's more capable of boosting testosterone than exogenous formulations. But unlike exogenous testosterone, clomiphene citrate preserves -- and possibly enhances -- sperm production. That makes drugs like clomiphene citrate one of only a few choices for men with low testosterone who want to father children. What kinds of testosterone-replacement treatment can be found? * The earliest form is the injection, which we use since it is cheap and since we faithfully become good testosterone levels in nearly everybody. The disadvantage is that a man needs to come in every couple of weeks to find a shot. A roller-coaster effect may also occur as blood testosterone levels peak and then return to research. Topical treatments help maintain a more uniform level of blood testosterone. The first kind of topical treatment was a patch, but it has a very high rate of skin irritation. In 1 study, as many as 40 percent of people that used the patch developed a reddish area on their skin. That limits its use. The most widely used testosterone preparation in the United States -- and the one I start almost everyone off with -- is a topical gel. There are just two brands: AndroGel and Testim. Based on my experience, it tends to be consumed to great levels in about 80% to 85% of guys, but that leaves a substantial number who do not consume enough for this to have a favorable effect. [For specifics on several different formulations, see table ] Are there any drawbacks to using dyes? How long does it take for them to work? Men who start using the implants need to come back in to have their testosterone levels measured again to be sure they're absorbing the proper amount. Our target is that the mid to upper range of normal, which generally means approximately 500 to 600 ng/dl. The concentration of testosterone in the blood really goes up quite quickly, in just a few doses. I usually measure it after 2 weeks, although symptoms may not change for a month or two. |