A Harvard Specialist shares his thoughts on testosterone-replacement therapy
An interview with Abraham Morgentaler, M.D.
It could be stated that testosterone is the thing that makes men, men. It gives them their characteristic deep voices, big muscles, and body and facial hair, differentiating them from girls. It stimulates the development of the genitals , plays a role in sperm production, fuels libido, and contributes to normal erections. Additionally, it boosts the production of red blood cells, boosts mood, and assists cognition.
Over time, the "machinery" which produces testosterone gradually becomes less powerful, and testosterone levels begin to fall, by approximately 1 percent a year, starting in the 40s. As guys get into their 50s, 60s, and beyond, they might begin to have signs and symptoms of low testosterone such as reduced sex drive and sense of vitality, erectile dysfunction, diminished energy, reduced muscle mass and bone density, and nausea. Taken together, these symptoms and signs are often called hypogonadism ("hypo" significance low functioning and"gonadism" speaking to the testicles). Researchers estimate that the illness affects anywhere from two to six million men in the United States. Yet it's an underdiagnosed problem, with just about 5% of these affected undergoing therapy.
Studies have revealed that testosterone-replacement therapy may provide a wide selection of benefits for men with hypogonadism, such as improved 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 can 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's developed particular experience in treating low testosterone levels. In this interview, Dr. Morgentaler shares his perspectives on current controversies, the treatment strategies he utilizes his own patients, and he thinks specialists should rethink the possible connection between testosterone-replacement therapy and prostate cancer.
Symptoms and diagnosisWhat symptoms and signs of low testosterone prompt the average man to see a doctor?
As a urologist, I have a tendency to see guys because they have sexual complaints. The main hallmark of reduced testosterone is low sexual libido or desire, but another can be erectile dysfunction, and some other guy who complains of erectile dysfunction should possess his testosterone level checked. Men can experience other symptoms, such as more trouble achieving an orgasm, less-intense orgasms, a much lesser amount of fluid out of ejaculation, and a sense of numbness in the penis when they see or experience something which would usually be arousing.
The more of these symptoms you will find, the more probable it is that a man has low testosterone. Many physicians tend to discount those"soft symptoms" as a normal part of aging, but they're often treatable and reversible by normalizing testosterone levels.
Aren't those the very same symptoms that men have when they are treated for benign prostatic hyperplasia, or BPH?
Not exactly. There are quite a few drugs that may reduce libido, such as the BPH drugs finasteride (Proscar) and dutasteride (Avodart). Those drugs can also reduce the quantity of the ejaculatory fluid, no wonder. But a reduction in orgasm intensity normally doesn't go along with treatment for BPH. Erectile dysfunction does not usually go together with it , though certainly if a person has less sex drive or less attention, it's more of a challenge to have a fantastic erection.
How do you determine whether or not a person 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 methods is far from perfect. Generally men with the lowest testosterone have the most symptoms and guys with highest testosterone have the least. But there are some guys who have reduced levels of testosterone in their blood and have no signs.
Looking at the biochemical numbers, The Endocrine Society* considers low testosterone to be a total testosterone level of less than 300 ng/dl, and I think that is a sensible guide. However, no one really agrees on a few. It is similar to diabetes, in which if your fasting sugar is over a certain level, they will say,"Okay, you've got it." With testosterone, that break point isn't quite as apparent.
| *Notice: The Endocrine Society recommends clinical practice guidelines with recommendations for who should and should not receive testosterone treatment. For you can try these out a complete copy of the guidelines, log on continue reading this to www.endo-society.org. |
Is total testosterone the right thing to be measuring? Or should we be measuring something else?
Well, this is just another area of confusion and good debate, but I don't think it's as confusing as it appears to be in the literature. When most doctors learned about testosterone in medical school, they learned about total testosterone, or all of the testosterone in the human body. However, about half of their testosterone that is circulating in the bloodstream is not available to the cells. It's tightly bound to a carrier molecule known as sex hormone--binding globulin, which we abbreviate as SHBG.
The available part of total testosterone is known as free testosterone, and it is readily available to cells. Nearly every laboratory has a blood test to measure free testosterone. Though it's just a small fraction of the total, the free testosterone level is a fairly good indicator of reduced testosterone. It is not perfect, but the correlation is greater than with testosterone.
This professional organization recommends testosterone therapy for men who have
- Low levels of testosterone in the blood (less than 300 ng/dl)
- symptoms of low testosterone.
Therapy is not recommended for men who have
- Breast or prostate cancer
- a nodule on the prostate which can be felt during a DRE
- a PSA higher than 3 ng/ml without additional analysis
- 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 of day, diet, or other elements influence testosterone levels?
For years, the recommendation has been to receive a testosterone value early in the morning since levels start to drop after 10 or even 11 a.m.. However, the data behind this recommendation were attracted to healthy young men. Two recent studies demonstrated little change in blood testosterone levels in men 40 and older within the course of this day. One reported no change in average testosterone until after 2 Between 6 and 2 p.m., it went down by 13 percent, a modest sum, and probably not enough to influence identification. Most guidelines still say it's important to perform the test in the morning, but for men 40 and over, it likely doesn't matter much, as long as they obtain their blood drawn before 6 or 5 p.m.
There are some rather interesting findings about diet. By way of example, it seems that individuals that have a diet low in protein have lower testosterone levels than men who eat more protein. But diet hasn't been researched thoroughly enough to make any clear recommendations.
FormulationsExogenous vs. endogenous testosterone
Within this guide, testosterone-replacement therapy refers to the treatment of hypogonadism with adrenal gland -- testosterone that is produced outside the body. Depending on the formula, treatment can lead to skin irritation, breast enlargement and tenderness, sleep apnea, acne, decreased sperm count, increased red blood cell count, and additional side effects.
At a recent prospective study, 36 hypogonadal men took a daily dose of clomiphene citrate for at least three months. Within four to six months, all of the guys had heightened levels of testosterone; none reported some side effects during the year they had been followed.
Since clomiphene citrate is not accepted by the FDA for use in males, little information exists about the long-term effects of carrying it (including the risk of developing prostate cancer) or if it's more effective at boosting testosterone than exogenous formulas. But unlike exogenous testosterone, clomiphene citrate preserves -- and potentially enriches -- sperm production. That makes drugs such as clomiphene citrate one of just a few choices for men with low testosterone who wish to father children.
What forms of testosterone-replacement treatment can be found? *
The oldest form is an injection, which we use because it is cheap and because we faithfully become good testosterone levels in almost everybody. The drawback is that a person needs to come in every couple of weeks to get a shot. A roller-coaster effect can also occur as blood testosterone levels peak and then return to research.
Topical therapies help maintain a more uniform amount of blood testosterone. The first kind of topical therapy was a patch, but it has a very large rate of skin irritation. In 1 study, as many as 40% of men who used the patch developed a reddish area on their skin. That restricts its use.
The most widely used testosterone preparation in the United States -- and the one I begin almost everyone off -- is a topical gel. There are two brands: AndroGel and Testim. According to my experience, it tends to be absorbed to good degrees in about 80% to 85% of guys, but leaves a significant number who do not absorb sufficient for it to have a favorable effect. [For specifics on several different formulations, see table below.]
Are there any drawbacks to using dyes? How much time does it require them to work?
Men who begin using the gels have to come back in to have their testosterone levels measured again to make sure they're absorbing the right quantity. Our goal is that the mid to upper assortment of normal, which generally means approximately 500 to 600 ng/dl. The concentration of testosterone in blood actually goes up quite quickly, within several doses. I normally measure it after 2 weeks, even although symptoms may not change for a month or two.