A Harvard Specialist shares his thoughts on testosterone-replacement therapy
It might be said that testosterone is what makes men, men. It gives them their characteristic deep voices, large muscles, and body and facial hair, differentiating them from women. 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% a year, beginning in the 40s. As men get into their 50s, 60s, and beyond, they may start to have signs and symptoms of low testosterone such as reduced libido and sense of energy, erectile dysfunction, diminished 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" referring to the testicles). Yet it's an underdiagnosed issue, with just about 5 percent of these affected undergoing therapy.
Various studies have revealed that testosterone-replacement therapy may offer a wide range of advantages for men with hypogonadism, such as enhanced libido, mood, cognition, muscle mass, bone density, and red blood cell production. 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 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 utilizes his own patients, and why he believes experts should reconsider the possible link between testosterone-replacement treatment and prostate cancer.
Symptoms and diagnosisWhat symptoms and signs of low testosterone prompt that the average person to find a physician?
As a urologist, I have a tendency to see guys because 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 guy who complains of erectile dysfunction should get his testosterone level checked. Men can experience other symptoms, like more difficulty achieving an orgasm, less-intense climaxes, a lesser amount of fluid out of 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 you will find, the more probable it is that a man has low testosterone. Many physicians tend to discount these"soft symptoms" as a normal part of aging, but they're often treatable and reversible by normalizing testosterone levels.
Are not 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 which 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. However a reduction in orgasm intensity normally does not go together with treatment 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 determine whether a man 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 symptoms and signs, and the correlation between those two approaches is far from perfect. Normally guys with the lowest testosterone have the most symptoms and men with maximum testosterone have the least. But there are a number of men who have low levels of testosterone in their blood and have no signs.
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 believe that is a reasonable guide. However, no one quite agrees on a few. It's not like diabetes, in which if your fasting glucose is above a certain level, they will say,"Okay, you've got it." With testosterone, that break point isn't quite as clear.
| *Notice: The Endocrine Society recommends clinical practice guidelines with recommendations for who should and shouldn't receive testosterone therapy. Watch"Endocrine Society recommendations summarized." For a try here complete copy navigate to this website of the instructions, 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 great debate, but I do not think it's as confusing as it appears to be in the literature. When most physicians learned about testosterone in medical school, they learned about overall testosterone, or all the testosterone in the body. But about half of their testosterone that is circulating in the bloodstream is not available to cells.
The available part of total testosterone is known as free testosterone, and it is readily available to cells. Though it's just a small portion of this overall, the free testosterone level is a fairly good indicator of low testosterone. It's not perfect, but the correlation is greater compared to testosterone.
This professional organization urges testosterone treatment for men who have
- Low levels of testosterone in the blood (less than 300 ng/dl)
- symptoms of low testosterone.
Therapy is not recommended for men who have
- Breast or prostate cancer
- a nodule on the prostate which may be felt during a DRE
- that a PSA higher than 3 ng/ml without additional analysis
- that a hematocrit greater than 50 percent or thick, viscous blood
- untreated obstructive sleep apnea
- severe lower urinary tract infections
- class III or helpful hints IV heart failure.
Do time of day, diet, or other factors affect testosterone levels?
For years, the recommendation has been to get a testosterone value early in the morning because levels start to drop after 10 or 11 a.m.. But the data behind that recommendation were drawn from healthy young men. Two recent studies showed little change in blood testosterone levels in men 40 and older over the course of the day. One reported no change in average testosterone till after 2 Between 2 and 6 p.m., it went down by 13 percent, a small sum, 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 over, it likely doesn't matter much, as long as they get their blood drawn before 5 or 6 p.m.
There are some very interesting findings about diet. For example, it seems that those that have a diet low in protein have lower testosterone levels than males who consume more protein. But diet hasn't been researched thoroughly enough to create any recommendations that are clear.
FormulationsExogenous vs. endogenous testosterone
In this article, testosterone-replacement treatment refers to the treatment of hypogonadism with exogenous testosterone -- testosterone that's produced outside the body. Depending on the formula, therapy can lead to skin irritation, breast enlargement and tenderness, sleep apnea, acne, reduced 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 three or more months. Within four to six months, each one the guys had increased levels of testosterone; none reported any side effects throughout the entire year they had been followed.
Because clomiphene citrate is not approved by the FDA for use in men, little information exists regarding the long-term ramifications of carrying it (including the risk of developing prostate cancer) or if it is more capable of boosting testosterone compared to exogenous formulations. But unlike adrenal gland, clomiphene citrate preserves -- and possibly enriches -- sperm production. That makes medication like clomiphene citrate one of just a few choices for men with low testosterone that want 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 get a shot. A roller-coaster effect may also occur as blood glucose levels peak and then return to research.
Topical therapies help preserve a more uniform level of blood glucose. The first form of topical treatment 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 on their skin. That restricts its use.
The most widely used testosterone preparation in the United States -- and also the one I start almost everyone off with -- is a topical gel. There are two brands: AndroGel and Testim. Based on my experience, it has a tendency to be absorbed to great levels in about 80% to 85 percent of guys, but that leaves a significant number who don't consume enough for it to have a favorable effect. [For details on several different formulations, see table below.]
Are there any downsides to using gels? How long does it require them to work?
Men who start using the implants need to come back in to have their testosterone levels measured again to be sure they're absorbing the proper quantity. Our target is that the mid to upper assortment of normal, which usually means approximately 500 to 600 ng/dl. The concentration of testosterone in blood really goes up quite fast, within several doses. I normally measure it after two weeks, even although symptoms may not change for a month or two.