A Harvard expert shares his thoughts on testosterone-replacement therapy
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 development 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 aids cognition.
As time passes, the testicular"machinery" which produces testosterone gradually becomes less powerful, and testosterone levels start to fall, by approximately 1% a year, starting in the 40s. As men get into their 50s, 60s, and beyond, they might start to have symptoms and signs of low testosterone like lower libido and sense of energy, erectile dysfunction, decreased energy, reduced muscle mass and bone density, and nausea. Taken together, these signs and symptoms 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 United States. Yet it is an underdiagnosed issue, with just about 5% of those affected undergoing therapy.
But little consensus exists on what constitutes low testosterone, when testosterone supplementation makes sense, or what risks patients face. 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 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 connection between testosterone-replacement treatment and prostate cancer.
Symptoms and diagnosisWhat signs and symptoms of low testosterone prompt the average man to see a doctor?
As a urologist, I have a tendency to observe guys since they have sexual complaints. The main hallmark of reduced testosterone is low sexual desire or libido, but another can be erectile dysfunction, and any man who complains of erectile dysfunction should get his testosterone level checked. Men may experience other symptoms, such as more difficulty achieving an orgasm, less-intense orgasms, a smaller amount of fluid out of ejaculation, and a sense of numbness in the manhood when they see or experience something which would usually be arousing.
The more of the symptoms you will find, the more probable it is that a man has low testosterone. Many physicians often discount those"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 men have when they're treated for benign prostatic hyperplasia, or BPH?
Not precisely. There are quite a few medications which may reduce libido, including the BPH drugs finasteride (Proscar) and dutasteride (Avodart). Those drugs can also decrease the quantity of the ejaculatory fluid, no wonder. But a reduction in orgasm intensity usually doesn't go together with therapy for BPH. Erectile dysfunction does not usually go along with it either, though surely if a person has less sex drive or less attention, it's more of a challenge to get a fantastic erection.
How can you determine whether or not a person is a candidate for testosterone-replacement treatment?
There are two ways that we determine whether somebody has low testosterone. One is a blood test and the other one is by characteristic signs and symptoms, and the correlation between these two methods is far from perfect. Normally guys with the lowest testosterone have the most symptoms and men with highest testosterone possess the least. However, there are some men who have reduced levels of testosterone in their blood and have no signs.
Looking purely at the biochemical amounts, 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 similar to 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 shouldn't receive testosterone therapy. |
Is complete testosterone the right thing to be measuring? Or if we are measuring something else?
This is another area of confusion and great discussion, but I don't think that it's as confusing as it appears to be from the literature. When most physicians learned about testosterone in medical school, they learned about overall testosterone, or all the testosterone in the human body. But about half of the testosterone that is circulating in the bloodstream isn't available to cells.
The available part of overall testosterone is called free testosterone, and it is readily available to the cells. Nearly every lab has a blood test to measure free testosterone. Though it's only a little fraction of this total, 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 urges testosterone therapy for men who have
- Reduced levels of testosterone in the blood (less than 300 ng/dl)
- symptoms of low testosterone.
Therapy is not Suggested for men who've
- Prostate or breast cancer
- a nodule on the prostate which can be felt during a DRE
- that a PSA greater than 3 ng/ml without additional analysis
- a hematocrit greater than 50 percent or thick, viscous blood
- untreated obstructive sleep apnea
- severe lower urinary tract symptoms
- class III or IV heart see it here failure.
Do time daily, diet, or other elements 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 even 11 a.m.. But the information behind that recommendation were drawn from 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 6 and 2 p.m., it went down by 13 percent, a modest amount, and probably insufficient to influence diagnosis. Most guidelines nevertheless say it is important to do the test in the morning, however 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 dietary supplements. For example, it seems that those that have a diet low in protein have lower testosterone levels than men who consume more protein. But diet has not been researched thoroughly enough to make any recommendations that are clear.
Exogenous vs. endogenous testosterone
In the following guide, testosterone-replacement treatment refers to the treatment of hypogonadism with exogenous testosterone -- testosterone that is manufactured outside the body. Based upon the formula, therapy can cause skin irritation, breast enlargement and tenderness, sleep apnea, acne, decreased sperm count, increased red blood cell count, along with additional side effects.
Within four to six months, each one the guys had increased levels of testosteronenone reported some side effects throughout the entire year they had been followed.
Since clomiphene citrate isn't approved by the FDA for use in men, little information exists about the long-term effects of taking it (including the risk of developing prostate cancer) or whether it's more capable of boosting testosterone compared to exogenous formulas. But unlike adrenal gland, clomiphene citrate maintains -- and potentially enriches -- sperm production. This makes medication such as clomiphene citrate one of just a few options for men with low testosterone who want to father children.
What forms of testosterone-replacement therapy are available? *
The oldest form is the injection, which we use because it's inexpensive and since we faithfully become fantastic 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 happen as blood glucose levels peak and then return to baseline. [See"Exogenous vs. endogenous testosterone," above.]
Topical therapies help maintain a more uniform amount of blood glucose. 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 percent of men who used the patch developed a red area on their skin. That limits its use.
The most widely used testosterone preparation from the United States -- and the one I start almost everyone off -- is a topical gel. Based on my experience, it tends to be absorbed to great degrees in about 80% to 85% of men, but leaves a substantial number who don't consume enough for it to have a favorable impact. [For specifics on various formulations, see table ]
Are there any drawbacks to using gels? How much time does it take for them to work?
Men who begin using the gels have to come back in to have their own testosterone levels measured again to be sure they are absorbing the proper amount. Our goal is the mid to upper range of normal, which generally means around 500 to 600 ng/dl. The concentration of testosterone in blood actually goes up quite fast, in just a few doses. I usually measure it after 2 weeks, although symptoms may not change for a month or two.