A Harvard Specialist shares his Ideas on testosterone-replacement Treatment
A meeting with Abraham Morgentaler, M.D.
It could be said that testosterone is the thing that makes guys, guys. It gives them their characteristic deep voices, large muscles, and facial and body hair, differentiating them from women. It stimulates the growth of the genitals at puberty, plays a role in sperm production, fuels libido, and leads to regular erections. It also boosts the production of red blood cells, boosts mood, and aids cognition.
As time passes, the testicular"machinery" that produces testosterone slowly becomes less effective, and testosterone levels start to fall, by approximately 1% a year, starting in the 40s. As men get in 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, decreased energy, decreased muscle mass and bone density, and anemia. Taken together, these symptoms and signs are often referred to as 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's an underdiagnosed problem, with only about 5% of these affected receiving treatment.
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 ailments and male sexual and reproductive problems. 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 uses with his patients, and he thinks experts should reconsider the possible connection between testosterone-replacement therapy and prostate cancer.
Symptoms and diagnosisWhat signs and symptoms of low testosterone prompt that the average man to see a doctor?
As a urologist, I tend to see guys because they have sexual complaints. The main hallmark of low testosterone is low sexual libido or desire, but another may be erectile dysfunction, and any guy who complains of erectile dysfunction must possess his testosterone level checked. Men can experience different symptoms, like more difficulty achieving an orgasm, less-intense orgasms, a much smaller quantity of fluid from ejaculation, and a sense of numbness in the penis when they see or experience something which would normally 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 decreasing testosterone levels.
Are not those the very same symptoms that men have when they're treated for benign prostatic hyperplasia, or BPH?
Not precisely. There are quite a few drugs which may reduce libido, including the BPH drugs finasteride (Proscar) and dutasteride (Avodart). Those drugs may also reduce the quantity of the ejaculatory fluid, no question. However a reduction in orgasm intensity normally does not go together with therapy for BPH. Erectile dysfunction does not usually go together with it , though certainly if a person has less sex drive or less interest, it is more of a challenge to get a good erection.
How can you decide whether or not a man is a candidate for testosterone-replacement treatment?
There are just two ways we determine whether somebody has low testosterone. One is a blood test and the other one is by characteristic symptoms and signs, and the correlation between these two methods is far from perfect. Normally guys with the lowest testosterone have the most symptoms and men with maximum testosterone possess the least. However, there are a number of guys who have low levels of testosterone in their blood and have no signs.
Looking at the biochemical numbers, The Endocrine Society* believes low testosterone for a total testosterone level of less than 300 ng/dl, and I think that is a reasonable guide. However, no one quite agrees on a number. 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 clear.
| *Note: The Endocrine Society recommends clinical practice guidelines with recommendations for who should and should not receive testosterone treatment. For a complete copy of Full Report the guidelines, log on to www.endo-society.org. |
Is total testosterone the right thing to be measuring? Or should we be measuring something else?
This is just another area of confusion and great debate, 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 heard about total testosterone, or all of the testosterone in the body. But about half of the testosterone that is circulating in the blood isn't readily available to the cells. It is tightly bound to a copyright 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 the cells. Almost every laboratory has a blood test to measure free testosterone. Even though it's only a small portion of this overall, the free testosterone level is a pretty good indicator of low testosterone. It is not ideal, but the significance is greater than with testosterone.
This professional organization recommends testosterone treatment for men who have both
Therapy is not Suggested for men who have
- Prostate or breast cancer
- a nodule on the prostate which can be felt during a DRE
- that a PSA higher than 3 ng/ml without further analysis
- that 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 because levels start to fall after 10 or 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 mature over the course of the day. One reported no change in typical testosterone until after 2 Between 2 and 6 p.m., it went down by 13%, a modest sum, and probably not enough to influence identification. Most guidelines still say it's important to do the test in the morning, however for men 40 and over, it probably doesn't matter much, as long as they get their blood drawn before 5 or 6 p.m.
There are some rather interesting findings about dietary supplements. By way of example, it appears that individuals who have a diet low in protein have lower testosterone levels than men who eat more protein. But diet hasn't been studied thoroughly enough to create any recommendations that are clear.
Within this article, 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, decreased sperm count, increased red blood cell count, along with additional side effects.
At a recent prospective study, 36 hypogonadal men took a daily dose of clomiphene citrate for three or more months. Within four to six weeks, all the men had heightened levels of testosteronenone reported any side effects during the entire year they had been followed.
Since 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 is more capable of boosting testosterone compared to exogenous formulations. But unlike adrenal gland, clomiphene citrate maintains -- and possibly enriches -- sperm production. This makes drugs like clomiphene citrate one of just a few choices for men with low testosterone that want to father children.
What kinds of testosterone-replacement treatment can be found? *
The earliest form is an injection, which we still use since it is inexpensive and since we faithfully get fantastic testosterone levels in nearly everybody. The drawback is that a man should come in every few weeks to get a shot. A roller-coaster effect may also happen as blood glucose levels peak and then return to baseline. [Watch"Exogenous vs. endogenous testosterone," above.]
Topical therapies help preserve a more uniform amount of blood testosterone. The first kind of topical treatment was a patch, but it has a quite large rate of skin irritation. In one study, as many as 40% of people that used the patch developed a reddish area on their skin. That limits its usage.
The most commonly used testosterone preparation from the United States -- and the one I start almost everyone off -- is a topical gel. There are two brands: AndroGel and Testim. According to my experience, it has a tendency to be absorbed to good degrees in about 80% to 85 percent of men, but that leaves a significant number who don't consume sufficient for it to have a positive impact. [For details on various formulations, see table ]
Are there any downsides to using gels? How long does it take for them to get the job done?
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 quantity. Our target is the mid to upper assortment of normal, which generally means around 500 to 600 ng/dl. The concentration of testosterone in the blood actually goes up quite quickly, within several doses. I normally measure it after 2 weeks, even though symptoms may not alter for a month or two.