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A Harvard Specialist shares his Ideas on testosterone-replacement therapy

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 body and facial hair, differentiating them from women. It stimulates the growth of the genitals , plays a role in sperm production, fuels libido, and contributes to normal erections. It also fosters the creation of red blood cells, boosts mood, and assists cognition.

As time passes, the testicular"machinery" which makes testosterone slowly becomes less effective, and testosterone levels start to drop, by approximately 1 percent per year, starting in the 40s. As guys get in their 50s, 60s, and beyond, they might begin to have symptoms and signs of low testosterone like reduced libido and sense of energy, erectile dysfunction, diminished energy, reduced muscle mass and bone density, and anemia. Taken together, these signs and symptoms are often referred to as hypogonadism ("hypo" significance low functioning and"gonadism" referring to the testicles). Yet it is an underdiagnosed issue, with just about 5% of these affected undergoing therapy.

Much of the current debate focuses on the long-held belief that testosterone can stimulate prostate cancer.

He has developed specific expertise in treating lower testosterone levels. In this interview, Dr. Morgentaler shares his views on current controversies, the treatment plans he uses with his patients, and why he believes specialists should rethink the possible connection between testosterone-replacement therapy and prostate cancer.

Symptoms and diagnosis

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

As a urologist, I have a tendency to see guys because they have sexual complaints. The main hallmark of low testosterone is reduced sexual desire or libido, but another may be erectile dysfunction, and any man who complains of erectile dysfunction must get his testosterone level checked. Men may experience different symptoms, such as more difficulty achieving an orgasm, less-intense climaxes, a smaller quantity of fluid out of 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 you will find, the more likely it is that a man has low testosterone. Many physicians tend to 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 same symptoms that men have when they are treated for benign prostatic hyperplasia, or BPH?

Not precisely. There are a number of medications which may lessen sex drive, including the BPH medication finasteride (Proscar) and dutasteride (Avodart). Those drugs may also decrease the amount of the ejaculatory fluid, no question. However a decrease in orgasm intensity usually does not go together with treatment for BPH. Erectile dysfunction does not usually go together with it , though surely if a person has less sex drive or less interest, it's more of a struggle to have a good erection.

How can you decide if 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 signs and symptoms, and the correlation between these two methods is far from perfect. Generally men with the lowest testosterone have the most symptoms and men with highest testosterone possess the least. But there are some men who have low levels of testosterone in their blood and have no symptoms.

Looking purely at the biochemical numbers, The Endocrine Society* considers low testosterone to be a total testosterone level of less than 300 ng/dl, and I think that's a reasonable guide. But no one quite agrees on a number. It's 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 is not quite as apparent.

*Notice: The Endocrine Society recommends clinical practice guidelines with recommendations for who should visit this site and should not receive testosterone treatment.

Is complete testosterone the ideal point to be measuring? Or if we are measuring something different?

This is just another area of confusion and great debate, but I don't think it's as confusing as it is apparently from the literature. When most physicians learned about testosterone in medical school, they heard about overall testosterone, or all of the testosterone in the body. But about half of the testosterone that is circulating in the blood is not available to the cells. It's tightly bound to a carrier molecule known as sex hormone--binding globulin, which we abbreviate as SHBG.

The available portion of overall testosterone is known as free testosterone, and it's readily available to the cells. Though it's only a small portion of this total, the free testosterone level is a pretty good indicator of low testosterone. It is not ideal, but the correlation is greater than with testosterone.

Endocrine Society recommendations outlined

This professional organization recommends testosterone therapy for men who have

Therapy is not Suggested for men who've

Breast or prostate cancer
a nodule on the prostate that can be felt during a DRE
a PSA higher than 3 ng/ml without further evaluation
that a hematocrit greater than 50 percent or thick, viscous blood
untreated obstructive sleep apnea
severe lower urinary tract symptoms

class III or IV visit homepage heart failure.

Do time of day, diet, or other elements affect testosterone levels?

For years, the recommendation was to get a testosterone value early in the morning because levels begin to drop after 10 or 11 a.m.. However, the data 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 until after 2 p.m. Between 6 and 2 p.m., it went down by 13%, a small amount, and probably not enough to affect diagnosis. Most guidelines nevertheless say it is important to perform the test in the morning, however for men 40 and above, it probably doesn't 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. For instance, it appears that individuals that have a diet low in protein have lower testosterone levels than males who consume more protein. But diet has not been studied thoroughly enough to make any clear recommendations.

Exogenous vs. endogenous testosterone

In the following guide, testosterone-replacement treatment refers to the treatment of hypogonadism with adrenal gland -- testosterone that is manufactured outside the body. Depending on the formula, therapy can cause skin irritation, breast tenderness and enlargement, sleep apnea, acne, reduced 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 at least three months. Within four to six weeks, each one the guys had heightened levels of testosterone; none reported any side effects during the entire year they had been followed.

Since clomiphene citrate isn't accepted 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 capable of boosting testosterone than exogenous formulations. But unlike adrenal gland, clomiphene citrate preserves -- and potentially enhances -- 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.

Formulations

What forms of testosterone-replacement treatment are available? *

The earliest form is an injection, which we use since it's inexpensive and because we reliably get good testosterone levels in nearly everybody. The disadvantage is that a man needs to come in every couple of weeks to get a shot. A roller-coaster effect can also happen as blood testosterone levels peak and then return to baseline. [Watch"Exogenous vs. endogenous testosterone," above.]

Topical treatments help maintain a more uniform level of blood testosterone. The first form of topical treatment has been a patch, but it has a very 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 restricts its usage.

The most commonly used testosterone preparation from the United States -- and also the one I start almost everyone off -- is a topical gel. There are just two brands: AndroGel and Testim. Based on my experience, it has a tendency to be absorbed to good degrees in about 80% to 85% of men, but that leaves a significant number who do not absorb sufficient for it to have a favorable effect. [For details on several different formulations, see table ]

Are there any drawbacks to using dyes? How much time does it take for them to get the job done?

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 right amount. Our target is that the mid to upper assortment of normal, which generally means approximately 500 to 600 ng/dl. The concentration of testosterone in blood really goes up quite fast, within a few doses. I normally measure it after 2 weeks, even although symptoms may not alter for a month or two.

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