A Harvard expert shares his Ideas on testosterone-replacement therapy
An interview with Abraham Morgentaler, M.D.
It could be stated that testosterone is the thing that makes guys, men. It gives them their characteristic deep voices, large muscles, and body and facial hair, differentiating them from girls. It stimulates the development of the genitals at puberty, plays a role in sperm production, fuels libido, and contributes to normal erections. It also fosters the production of red blood cells, boosts mood, and aids cognition.
Over time, the testicular"machinery" that makes testosterone gradually becomes less effective, and testosterone levels start to fall, by about 1% per year, starting in the 40s. As guys get in their 50s, 60s, and beyond, they might begin to have symptoms and signs of low testosterone like reduced libido and sense of energy, erectile dysfunction, decreased energy, decreased muscle mass and bone density, and nausea. Taken together, these symptoms and signs are often referred to as hypogonadism ("hypo" significance low working and"gonadism" speaking to the testicles). Yet it's an underdiagnosed problem, with only about 5% of those affected receiving treatment.
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 sexual and reproductive difficulties. He's developed specific experience in treating lower testosterone levels. In this interview, Dr. Morgentaler shares his perspectives on current controversies, the treatment plans he uses with his own patients, and he believes 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 average man to find a physician?
As a urologist, I tend to observe guys because they have sexual complaints. The primary hallmark of reduced testosterone is reduced sexual desire or libido, but another can be erectile dysfunction, and some other man who complains of erectile dysfunction should possess his testosterone level checked. Men may experience other symptoms, like more trouble achieving an orgasm, less-intense orgasms, a smaller amount of fluid out of ejaculation, and a sense of numbness in the penis when they see or experience something which would normally be arousing.
The more of these symptoms there are, the more likely it is that a man has low testosterone. Many physicians often dismiss those"soft symptoms" as a normal part of aging, however, they are often treatable and reversible by decreasing testosterone levels.
Aren't those the same symptoms that guys have when they're treated for benign prostatic hyperplasia, or BPH?
Not precisely. There are a number of medications that may lessen sex drive, such as the BPH drugs finasteride (Proscar) and dutasteride (Avodart). Those drugs may also decrease the quantity of the ejaculatory fluid, no question. But a decrease in orgasm intensity usually doesn't go along with therapy for BPH. Erectile dysfunction does not usually go together with it either, though surely if somebody has less sex drive or less attention, it's more of a struggle to get a fantastic erection.
How do you decide whether a person is a candidate for testosterone-replacement therapy?
There are just two ways that we determine whether someone has low testosterone. One is a blood test and the other is by characteristic signs and symptoms, and the correlation between those two approaches is far from perfect. Normally men with the lowest testosterone have the most symptoms and guys with highest testosterone have the least. However, there are a number of guys who have reduced levels of testosterone in their blood and have no symptoms.
Looking at the biochemical numbers, The Endocrine Society* believes low testosterone to be a total testosterone level of less than 300 ng/dl, and I believe that's a reasonable guide. However, no one quite agrees on a number. It is not like diabetes, where if your fasting sugar is above a certain level, they'll say,"Okay, you've got it." With testosterone, that break point isn't quite as clear.
| *Note: The Endocrine Society recommends clinical practice guidelines with recommendations for who should and should not receive testosterone my review here therapy. For a complete copy of the click for more info instructions, my sources log on to www.endo-society.org. |
Is total testosterone the ideal point to be measuring? Or should we be measuring something else?
This is just another area of confusion and good discussion, but I do not think it's as confusing as it is apparently from the literature. When most doctors learned about testosterone in medical school, they learned about total testosterone, or all of the testosterone in the body. But about half of their testosterone that's circulating in the blood isn't available to cells.
The available portion of overall testosterone is known as free testosterone, and it is readily available to the cells. Almost every lab has a blood test to measure free testosterone. Though it's just a little fraction of this overall, the free testosterone level is a pretty good indicator of low testosterone. It is not perfect, but the significance is greater compared to testosterone.
This professional organization urges testosterone therapy for men who have both
- Low levels of testosterone in the blood (less than 300 ng/dl)
- symptoms of low testosterone.
Therapy Isn't Suggested for men who've
- Breast or prostate cancer
- a nodule on the prostate which may be felt during a DRE
- a PSA greater than 3 ng/ml without further evaluation
- a hematocrit greater than 50% or thick, viscous blood
- untreated obstructive sleep apnea
- severe lower urinary tract symptoms
- class III or IV heart failure.
Do time of day, 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 begin to drop after 10 or 11 a.m.. But 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 over the course of this day. One reported no change in typical testosterone until after 2 p.m. Between 2 and 6 p.m., it went down by 13%, a modest amount, and probably insufficient to affect identification. Most guidelines nevertheless say it is important to perform the evaluation in the morning, however for men 40 and above, it probably does not matter much, provided that they obtain their blood drawn before 5 or 6 p.m.
There are some very interesting findings about diet. By way of instance, it seems that individuals who have a diet low in protein have lower testosterone levels than men who eat more protein. But diet has not been researched thoroughly enough to make any recommendations that are clear.
In the following guide, testosterone-replacement therapy refers to the treatment of hypogonadism with exogenous testosterone -- testosterone that is produced outside the body. Based on the formulation, therapy can lead to skin irritation, breast tenderness and enlargement, sleep apnea, acne, reduced sperm count, increased red blood cell count, and additional side effects.
Preliminary studies have proven that clomiphene citrate (Clomid), a drug generally prescribed to stimulate ovulation in women struggling with infertility, can foster the production of natural testosterone, termed nitric oxide, in men. Within four to six months, all of the men had heightened levels of testosteronenone reported some side effects throughout 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 ramifications of taking it (such as the probability of developing prostate cancer) or whether it's more capable of boosting testosterone than exogenous formulas. But unlike adrenal gland, clomiphene citrate preserves -- and potentially enhances -- sperm production. This makes medication such as clomiphene citrate one of only a few options for men with low testosterone who wish to father children.
What kinds of testosterone-replacement therapy can be found? *
The oldest form is the injection, which we still use since it's cheap and because we faithfully get fantastic testosterone levels in nearly everybody. The drawback is that a man should come in every few weeks to find a shot. A roller-coaster effect can also happen as blood testosterone levels peak and then return to research. [See"Exogenous vs. endogenous testosterone," above.]
Topical treatments help maintain a more uniform amount of blood testosterone. The first kind of topical therapy was a patch, but it has a quite high rate of skin irritation. In 1 study, as many as 40% of people that used the patch developed a red area in their skin. That limits its usage.
The most commonly used testosterone preparation in the United States -- and also the one I start almost everyone off with -- is a topical gel. According to my experience, it tends to be consumed to great levels in about 80% to 85 percent of guys, but that leaves a significant number who do not absorb enough for this to have a positive effect. [For details on various formulations, see table ]
Are there any drawbacks to using dyes? How much time does it take for them to get the job done?
Men who begin using the gels have to come back in to have their testosterone levels measured again to make certain they're absorbing the right quantity. Our goal is the mid to upper range of normal, which generally means approximately 500 to 600 ng/dl. The concentration of testosterone in blood really goes up quite fast, within a few doses. I normally measure it after 2 weeks, even though symptoms may not change for a month or two.