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A Harvard expert shares his thoughts on testosterone-replacement therapy

It could be stated that testosterone is what makes guys, men. It gives them their characteristic deep voices, big muscles, and facial and body hair, distinguishing them from women. It stimulates the development of the genitals at puberty, plays a role in sperm production, fuels libido, and leads to regular erections. Additionally, it boosts the creation 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 begin 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 referred to as hypogonadism ("hypo" significance low functioning 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 these 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 diseases and male reproductive and sexual difficulties. He has developed particular experience in treating lower testosterone levels. In this interview, Dr. Morgentaler shares his perspectives on current controversies, the treatment plans he utilizes his patients, and he thinks specialists should rethink the potential connection between testosterone-replacement treatment and prostate cancer.

Symptoms and diagnosis

What signs and symptoms of low testosterone prompt the average man to see a physician?

As a urologist, I have a tendency to observe guys because they have sexual complaints. The primary 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 different symptoms, like more trouble achieving an orgasm, less-intense climaxes, a much lesser quantity 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, however, they are often treatable and reversible by normalizing testosterone levels.

Aren't those the very same symptoms that guys have when they are treated for benign prostatic hyperplasia, or BPH?

Not precisely. There are quite a few medications which 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. However a decrease in orgasm intensity normally does not go along with treatment for BPH. Erectile dysfunction does not usually go along with it either, though certainly if somebody has less sex drive or less attention, it is more of a struggle to get a good erection.

How can you decide if 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 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 guys with highest testosterone have the least. However, there are a number of guys who have low levels of testosterone in their blood and have no symptoms.

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 sensible guide. But no one really agrees on a few. It's similar to diabetes, in which if your fasting glucose is over a certain level, they will say,"Okay, you've got it." With testosterone, that break point is not quite as clear.

*Notice: The Endocrine Society publishes clinical practice guidelines with recommendations for who should and shouldn't receive testosterone treatment. See"Endocrine Society next page recommendations summarized."

Is complete testosterone the ideal thing to be measuring? Or if we are measuring something else?

This is just another area of confusion and great discussion, but I don't think it's as confusing as it is apparently in the literature. When most physicians learned about testosterone in medical school, they learned about total testosterone, or all of the testosterone in the body. However, about half of the testosterone that is circulating in the bloodstream isn't readily available to the cells.

The biologically available portion of total testosterone is known as free testosterone, and it's readily available to cells. Almost every laboratory has a blood test to measure free testosterone. Even though it's just a small portion of the overall, the free testosterone level is a pretty good indicator of reduced testosterone. It's not ideal, but the correlation is greater compared to total testosterone.

This professional organization recommends testosterone treatment for men who have both

  • Low levels of testosterone in the blood (less than 300 ng/dl)
  • symptoms of low testosterone.

Therapy Isn't 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% 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 influence 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.. But the information behind that recommendation were attracted to 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 2 and 6 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 evaluation in the morning, however for men 40 and above, it probably does not matter much, provided that they get their blood drawn before 5 or 6 p.m.

There are a number of rather interesting findings about diet. By way of instance, it appears that individuals that have a diet low in protein have lower testosterone levels than males who consume more protein. But diet hasn't been studied thoroughly enough to create any clear recommendations.

Within the following article, testosterone-replacement treatment refers to the treatment of hypogonadism with adrenal gland -- testosterone that is manufactured outside the body. Depending upon the formula, therapy can lead to 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 any side effects throughout the entire year they had been followed.

Since clomiphene citrate isn't accepted by the FDA for use in males, little information exists regarding the long-term ramifications of carrying it (such as the probability of developing prostate cancer) or if 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 that wish to father children.

What forms of testosterone-replacement therapy are available? *

The oldest form is an injection, which we still use because it's inexpensive and since we faithfully become good testosterone levels in nearly everybody. The disadvantage is that a man should come in every couple of weeks to find a shot. A roller-coaster effect may also occur as blood testosterone levels peak and then return to research. [Watch"Exogenous vs. endogenous testosterone," above.]

Topical treatments help maintain a more uniform level of blood testosterone. The first kind of topical treatment has been a patch, but it has a very high rate of skin irritation. In one study, as many as 40 percent of people that used the patch developed a red area on their skin. That restricts its usage.

The most widely used testosterone preparation in the United States -- and the one I begin almost everyone off -- is a topical gel. The gel comes in tiny tubes or within a special dispenser, and you rub it on your shoulders or upper arms once a day. Based on my experience, it has a tendency to be consumed to good levels in about 80% to 85 percent of men, but that leaves a significant number who do not 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 long does it take for them to get the job done?

Men who start using the gels have to come back in to have their own testosterone levels measured again to make sure they are absorbing the right quantity. Our target is the mid to upper assortment of normal, which usually means approximately 500 to 600 ng/dl. The concentration of testosterone in the blood actually goes up quite fast, within several doses. I normally measure it after two weeks, even though symptoms may not change for a month or two.

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