A Harvard expert shares his Ideas on testosterone-replacement therapy
An interview with Abraham Morgentaler, M.D.
It might be said that testosterone is the thing that makes men, men. It gives them their characteristic deep voices, big muscles, and facial and body hair, differentiating them from women. It stimulates the development of the genitals , 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 assists cognition.
Over time, the testicular"machinery" which makes 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 signs and symptoms of low testosterone like lower sex drive and sense of energy, erectile dysfunction, decreased energy, decreased muscle mass and bone density, and nausea. Taken together, these signs and symptoms are often referred to as hypogonadism ("hypo" meaning low functioning and"gonadism" speaking to the testicles). Researchers estimate that the condition affects anywhere from two to six million men in the United States. Yet it's an underdiagnosed problem, with only about 5 percent of those affected undergoing therapy.
But little consensus exists on what constitutes low testosterone, when testosterone supplementation makes sense, or what dangers patients face. 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 ailments and male sexual and reproductive difficulties. He's developed particular 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 believes 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 physician?
As a urologist, I tend to see guys since they have sexual complaints. The main hallmark of low testosterone is reduced sexual desire or libido, but another can be erectile dysfunction, and any man who complains of erectile dysfunction must possess his testosterone level checked. Men can experience other symptoms, such as more difficulty achieving an orgasm, less-intense orgasms, a much lesser quantity of fluid from ejaculation, and a feeling of numbness in the manhood 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 discount those"soft symptoms" as a normal part of aging, however, they're often treatable and reversible by decreasing testosterone levels.
Are not those the very same symptoms that guys have when they are treated for benign prostatic hyperplasia, or BPH?
Not exactly. There are a number of drugs that may lessen sex drive, 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 normally does not go together with therapy for BPH. Erectile dysfunction does not usually go along with it either, though certainly if somebody has less sex drive or less interest, it's more of a challenge to have a fantastic erection.
How can you decide whether a man is a candidate for testosterone-replacement therapy?
There are just two ways we determine whether somebody has low testosterone. One is a blood test and the other is by characteristic symptoms and signs, and the correlation between these two approaches is far from perfect. Normally guys with the lowest testosterone have the most symptoms and guys with maximum testosterone possess the least. However, there are a number of men who have low levels of testosterone in their blood and have no symptoms.
Looking purely at the biochemical amounts, The Endocrine Society* believes low testosterone for a entire testosterone level of less than 300 ng/dl, and I believe that's a reasonable guide. But no one really agrees on a number. It's not like diabetes, in which if your fasting sugar is over a certain level, they'll say,"Okay, you've got it." With testosterone, that break point is not quite as apparent.
| *Notice: The Endocrine Society publishes clinical practice guidelines with recommendations for who should and shouldn't receive testosterone therapy. For a complete copy of these instructions, log Recommended Reading on to www.endo-society.org. |
Is complete testosterone the ideal thing to be measuring? Or if we are measuring something different?
This is another area of confusion and great debate, but I do not think that it's as confusing as it appears to be in the literature. When most doctors learned about testosterone in medical school, they heard about overall testosterone, or all of the testosterone in the body. However, about half of their testosterone that is circulating in the blood is not readily available to cells. It is closely bound to a carrier molecule called sex hormone--binding globulin, which we abbreviate as SHBG.
The biologically available portion of total testosterone is called free testosterone, and it is readily available to the cells. Almost every laboratory has a blood test to measure free testosterone. Even though it's just a small fraction of this total, the free testosterone level is a fairly good indicator of reduced testosterone. It's not ideal, but the correlation is greater compared to total testosterone.
This professional organization urges testosterone therapy for men who have both
- Reduced levels of testosterone in the blood (less than 300 ng/dl)
- symptoms of low testosterone.
Therapy is not Suggested for men who have
- Breast or prostate cancer
- a nodule on the prostate that can be felt during a DRE
- that a PSA greater than 3 ng/ml without additional evaluation
- a hematocrit greater than 50 percent or thick, viscous blood
- untreated obstructive sleep apnea
- severe lower urinary tract symptoms
- class III or IV heart failure.
Do time daily, diet, or other elements affect testosterone levels?
For many 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 that recommendation were attracted to healthy young men. Two recent studies showed 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 2 and 6 p.m., it went down by 13 percent, a small amount, and probably insufficient to affect diagnosis. Most guidelines still say it is important to perform the test in the morning, but for men 40 and over, it likely doesn't matter much, as long as they get their blood drawn before 6 or 5 p.m.
There are a number of very interesting findings about diet. By way of instance, it appears that individuals who have a diet low in protein have lower testosterone levels than males who eat more protein. But diet hasn't been researched thoroughly enough to create any clear recommendations.
Within the following article, testosterone-replacement therapy refers to the treatment of hypogonadism with exogenous testosterone -- testosterone that's produced outside the body. Based upon the formulation, treatment can cause skin irritation, breast tenderness and enlargement, sleep apnea, acne, decreased sperm count, increased red blood cell count, along with additional side effects.
In a recent prospective study, 36 hypogonadal men took a daily dose of clomiphene citrate for at least three months. 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 is more capable of boosting testosterone than exogenous formulations. But unlike exogenous testosterone, clomiphene citrate preserves -- and possibly enriches -- sperm production. This makes medication such as clomiphene citrate one of just a few choices for men with low testosterone who want to father children.
FormulationsWhat forms of testosterone-replacement therapy are available? *
The oldest form is the injection, which we use since it's inexpensive and because we reliably get good testosterone levels in nearly everybody. The disadvantage is that a person should come in every couple of weeks to find a shot. A roller-coaster effect may also happen as blood glucose levels peak and return to research.
Topical therapies help maintain a more uniform level of blood testosterone. The first form 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 people that used the patch developed a reddish area on their skin. That limits its use.
The most commonly 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. The gel comes in miniature tubes or in a unique dispenser, and you rub it on your shoulders or upper arms once a day. According to my experience, it has a tendency to be consumed to great levels in about 80% to 85% of men, but leaves a significant number who do not consume enough for it to have a positive impact. [For details on various formulations, see table below.]
Are there any downsides to using dyes? How long 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 target is that the mid to upper assortment of normal, which usually means around 500 to 600 ng/dl. The concentration of testosterone in blood actually goes up quite quickly, in just a few doses. I usually measure it after 2 weeks, although symptoms may not alter for a month or two.