A Harvard Specialist shares his thoughts on testosterone-replacement therapy
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 women. It stimulates the development of the genitals at puberty, plays a role in sperm production, fuels libido, and contributes to regular erections. It also fosters the creation of red blood cells, boosts mood, and aids cognition.
Over time, the "machinery" which produces testosterone gradually becomes less effective, 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 symptoms and signs of low testosterone such as reduced libido 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" significance 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 issue, with only about 5 percent of those affected undergoing therapy.
But little consensus exists about what constitutes low testosterone, when testosterone supplementation makes sense, or what risks patients face.
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 sexual and reproductive problems. He has developed specific expertise in treating lower testosterone levels. In this interview, Dr. Morgentaler shares his perspectives on current controversies, the treatment strategies he utilizes his own patients, and he believes experts should reconsider the potential link between testosterone-replacement therapy and prostate cancer.
Symptoms and diagnosisWhat symptoms and signs of low testosterone prompt the typical man to see a physician?
As a urologist, I tend to observe guys because they have sexual complaints. The main hallmark of low 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, like more trouble achieving an orgasm, less-intense orgasms, a much smaller quantity of fluid from ejaculation, and a sense of numbness in the manhood when they see or experience something that would normally be arousing.
The more of these symptoms you will find, the more likely it is that a man has low testosterone. Many physicians tend to discount those"soft symptoms" as a normal part of aging, but they are often treatable and reversible by decreasing testosterone levels.
Are not those the same symptoms that guys have when they are treated for benign prostatic hyperplasia, or BPH?
Not exactly. There are a number of medications which may lessen sex drive, including the BPH medication finasteride (Proscar) and dutasteride (Avodart). Those drugs may also decrease the amount of the ejaculatory fluid, no wonder. However a reduction in orgasm intensity normally does not go along with treatment for BPH. Erectile dysfunction does not ordinarily go together with it , though certainly if a person has less sex drive or less attention, it is more of a challenge to get a good erection.
How do you decide if or not a person is a candidate for testosterone-replacement therapy?
There are two ways that we determine whether somebody has reduced testosterone. One is a blood test and the other one is by characteristic signs and symptoms, and the correlation between these two approaches is far from ideal. Generally men with the lowest testosterone have the most symptoms and men with highest testosterone have the least. But there are some men who have low 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's a sensible guide. However, no one really agrees on a few. It is not like 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 official source testosterone treatment. For a complete click reference copy of the guidelines, log on to www.endo-society.org. |
Is total testosterone the right thing to be measuring? Or should we be measuring something different?
This is just another area of confusion and good discussion, but I do not think it's as confusing as it appears to be in the literature. When most doctors learned about testosterone in medical school, they heard about total testosterone, or all the testosterone in the body. But about half of their testosterone that is circulating in the blood is not available to the cells. It's closely bound to a carrier molecule known as sex hormone--binding globulin, which we abbreviate as SHBG.
The available portion of overall testosterone is called free testosterone, and it's readily available to the cells. Though it's only a small portion of this total, the free testosterone level is a pretty good indicator of low testosterone. It is not ideal, but the correlation is greater than with testosterone.
Endocrine Society recommendations outlinedThis professional organization recommends testosterone therapy for men who have Therapy Isn't Suggested for men who have
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Do time of day, diet, or other elements influence testosterone levels?
For years, the recommendation was to get a testosterone value early in the morning since levels begin to drop after 10 or even 11 a.m.. However, the data behind this recommendation were drawn from healthy young men. Two recent studies showed little change in blood glucose levels in men 40 and older within the course of the day. One reported no change in average testosterone till after 2 p.m. Between 6 and 2 p.m., it went down by 13%, a modest sum, and probably not enough to affect diagnosis. Most guidelines nevertheless say it is important to do the evaluation in the morning, but for men 40 and over, it probably does not 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 has not been studied thoroughly enough to create any recommendations that are clear.
In this guide, testosterone-replacement therapy refers to the treatment of hypogonadism with adrenal gland -- testosterone that is produced outside the body. Depending upon the formulation, therapy can lead to skin irritation, breast enlargement and tenderness, sleep apnea, acne, decreased sperm count, increased red blood cell count, and additional side effects.
Within four to six weeks, all 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 (such as the risk of developing prostate cancer) or if it's more effective at boosting testosterone compared to exogenous formulations. But unlike exogenous testosterone, clomiphene citrate maintains -- and potentially enhances -- sperm production. That makes drugs such as clomiphene citrate one of only a few choices for men with low testosterone that wish to father children.
FormulationsWhat forms of testosterone-replacement therapy can be found? *
The earliest form is an injection, which we still use because it is cheap and since we reliably get good testosterone levels in almost everybody. The drawback is that a person should come in every few weeks to get a shot. A roller-coaster effect can also happen as blood glucose levels peak and return to research. [Watch"Exogenous vs. endogenous testosterone," above.]
Topical treatments help preserve a more uniform amount of blood glucose. The first form of topical therapy was a patch, but it has a very high rate of skin irritation. In one study, as many as 40 percent of people that used the patch developed a reddish area in their skin. That restricts its use.
The most commonly used testosterone preparation in the United States -- and the one I start almost everyone off -- is a topical gel. According to my experience, it has a tendency to be consumed to great degrees in about 80% to 85 percent of guys, but leaves a substantial number who don't absorb enough for it to have a positive effect. [For specifics on various formulations, see table ]
Are there any downsides to using dyes? How long does it take for them to work?
Men who start using the gels have to come back in to have their testosterone levels measured again to make certain they are absorbing the proper amount. Our target is the mid to upper range of normal, which generally means around 500 to 600 ng/dl. The concentration of testosterone in the blood actually goes up quite fast, in just several doses. I normally measure it after two weeks, though symptoms may not alter for a month or two.