A Harvard Specialist shares his Ideas on testosterone-replacement Treatment
An interview with Abraham Morgentaler, M.D.
It could be stated that testosterone is the thing that makes guys, guys. 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 , plays a role in sperm production, fuels libido, and contributes to normal erections. It also boosts the creation of red blood cells, boosts mood, and assists cognition.
As time passes, the testicular"machinery" which produces testosterone gradually becomes less powerful, and testosterone levels begin to fall, by about 1 percent per year, starting in the 40s. As guys get in their 50s, 60s, and beyond, they may start to have signs and symptoms of low testosterone like reduced sex drive and sense of vitality, 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 functioning and"gonadism" referring to the testicles). Yet it's an underdiagnosed issue, 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 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 problems. He's developed particular expertise in treating low testosterone levels. In this interview, Dr. Morgentaler shares his perspectives on current controversies, the treatment plans he uses with his patients, and why he thinks specialists should rethink the potential link between testosterone-replacement therapy and prostate cancer.
Symptoms and diagnosisWhat symptoms and signs of low testosterone prompt the typical man to find a physician?
As a urologist, I tend to see men since they have sexual complaints. The primary hallmark of reduced testosterone is low sexual libido or desire, but another can be erectile dysfunction, and some other man who complains of erectile dysfunction must possess his testosterone level checked. Men may experience other symptoms, like more difficulty achieving an orgasm, less-intense orgasms, a lesser amount of fluid from ejaculation, and a feeling of numbness in the penis when they see or experience something which would normally be arousing.
The more of the symptoms there are, the more probable it is that a man has low testosterone. Many physicians often dismiss these"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 are treated for benign prostatic hyperplasia, or BPH?
Not precisely. There are quite a few drugs that may reduce libido, such as the BPH drugs finasteride (Proscar) and dutasteride (Avodart). Those drugs can also decrease the quantity of the ejaculatory fluid, no question. However a reduction in orgasm intensity usually doesn't go together with treatment for BPH. Erectile dysfunction does not ordinarily go along with it , though surely if somebody has less sex drive or less interest, it's more of a struggle to get a fantastic erection.
How do you determine if a man is a candidate for testosterone-replacement therapy?
There are two ways we determine whether someone has low testosterone. One is a blood test and the other one is by characteristic signs and symptoms, and the correlation between those two methods is far from perfect. Normally men with the lowest testosterone have the most symptoms and guys with maximum testosterone have the least. But there are a number of men who have reduced levels of testosterone in their blood and have no symptoms.
Looking purely at the biochemical amounts, The Endocrine Society* considers low testosterone for a total testosterone level of less than 300 ng/dl, and I think that's a reasonable guide. However, no one quite agrees on a number. It is not like diabetes, where if your fasting glucose is above a certain level, they'll say,"Okay, you've got it." With testosterone, that break point isn't quite as apparent.
| *Note: The Endocrine Society recommends clinical practice guidelines with recommendations for who should and shouldn't receive testosterone therapy. Watch"Endocrine Society recommendations summarized." |
Is complete testosterone the ideal point to be measuring? Or if we are measuring something different?
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 heard about total testosterone, or all the testosterone in the human body. But about half of the testosterone that is circulating in the bloodstream isn't readily available to the cells. It's closely bound to a carrier molecule called sex hormone--binding globulin, which we abbreviate as SHBG.
The biologically available part of total testosterone is known as free testosterone, and it's readily available to the cells. Nearly every laboratory has a blood test to measure free testosterone. Though it's just a little fraction of this overall, the free testosterone level is a fairly good indicator of reduced testosterone. It is not ideal, but the correlation is greater than with total testosterone.
This professional organization urges testosterone therapy for men who have
Therapy is not recommended for men who have
- Breast or prostate cancer
- a nodule on the prostate that may be felt during a DRE
- a PSA higher than 3 ng/ml without further analysis
- that a hematocrit greater than 50 percent or thick, viscous blood
- untreated obstructive sleep apnea
- severe lower urinary tract infections
- class III click this or IV anonymous heart failure.
Do time of day, diet, or other factors affect testosterone levels?
For years, the recommendation was to receive a testosterone value early in the morning since levels begin to fall after 10 or even 11 a.m.. But the data behind that recommendation were drawn from healthy young men. Two recent studies demonstrated little change in blood glucose levels in men 40 and mature within the course of the day. One reported no change in typical testosterone until after 2 Between 6 and 2 p.m., it went down by 13%, a small amount, and probably insufficient to influence diagnosis. Most guidelines nevertheless say it's important to perform the evaluation in the morning, but for men 40 and above, it likely does not matter much, provided that they get their blood drawn before 6 or 5 p.m.
There are a number of rather interesting findings about dietary supplements. By way of example, it appears that those who have a diet low in protein have lower testosterone levels than men who eat more protein. But diet hasn't been researched thoroughly enough to create any clear recommendations.
FormulationsExogenous vs. endogenous testosterone
Within this article, testosterone-replacement treatment refers to the treatment of hypogonadism with exogenous testosterone -- testosterone that's manufactured outside the body. Based upon the formulation, therapy can lead to skin irritation, breast enlargement and tenderness, sleep apnea, acne, reduced sperm count, increased red blood cell count, and other side effects.
Preliminary research has shown that clomiphene citrate (Clomid), a drug generally prescribed to stimulate ovulation in women struggling with infertility, can boost the production of natural testosterone, known as endogenous testosterone, in men. In 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 increased levels of testosterone; none reported some side effects during the entire year they had been followed.
Because clomiphene citrate isn't approved by the FDA for use in men, little information exists regarding the long-term ramifications of taking it (including the risk of developing prostate cancer) or if it's more effective at boosting testosterone compared to exogenous formulas. But unlike exogenous testosterone, clomiphene citrate preserves -- and possibly enhances -- sperm production. That makes drugs like clomiphene citrate one of only a few choices for men with low testosterone that want to father children.
What kinds of testosterone-replacement therapy are available? *
The oldest form is an injection, which we still use because it's inexpensive and because we faithfully become fantastic 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 may also occur as blood testosterone levels peak and then return to baseline.
Topical therapies help maintain a more uniform amount of blood testosterone. The first form of topical therapy has been 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 red area on their skin. That restricts its use.
The most commonly used testosterone preparation from the United States -- and the one I begin almost everyone off -- is a topical gel. There are just two brands: AndroGel and Testim. The gel comes from tiny tubes or in a special dispenser, and you rub it on your shoulders or upper arms once a day. Based on my experience, it tends to be consumed to good levels in about 80% to 85 percent of guys, but leaves a substantial number who don't absorb enough for this to have a positive effect. [For details on several different formulations, see table below.]
Are there any downsides to using dyes? How much time does it take for them to get the job done?
Men who begin using the implants need to return in to have their testosterone levels measured again to be sure they are absorbing the right quantity. Our target is that the mid to upper range of normal, which usually means around 500 to 600 ng/dl. The concentration of testosterone in the blood actually goes up quite quickly, in just a few doses. I usually measure it after two weeks, although symptoms may not alter for a month or two.