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A Harvard Specialist shares his Ideas on testosterone-replacement Treatment

An interview with Abraham Morgentaler, M.D.

It might be said that testosterone is the thing that makes men, guys. It gives them their characteristic deep voices, large muscles, and body and facial hair, distinguishing them from girls. It stimulates the growth of the genitals at puberty, plays a role in sperm production, fuels libido, and contributes to regular erections. It also 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 drop, by approximately 1% per year, starting in the 40s. As men get in their 50s, 60s, and beyond, they might start to have symptoms and signs of low testosterone such as lower libido and sense of vitality, erectile dysfunction, decreased energy, decreased 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" speaking to the testicles). Researchers estimate that the illness affects anywhere from two to six million men in the United States. Yet it's an underdiagnosed issue, with only about 5% of these affected undergoing therapy.

Studies have revealed that testosterone-replacement therapy can offer a wide range of advantages for men with hypogonadism, such as improved 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 sexual and reproductive difficulties. He's developed specific expertise in treating low testosterone levels. In this interview, Dr. Morgentaler shares his views 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 typical person to find a doctor?

As a urologist, I tend to see men since they have sexual complaints. The main hallmark of reduced 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 difficulty achieving an orgasm, less-intense orgasms, a smaller amount of fluid from ejaculation, and a feeling 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 decreasing testosterone levels.

Are not those the very same symptoms that men have when they're 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 may also reduce the quantity of the ejaculatory fluid, no wonder. However a decrease in orgasm intensity usually doesn't go along with treatment for BPH. Erectile dysfunction does not usually go along with it either, though certainly if a person has less sex drive or less attention, it is more of a struggle to have a good erection.

How do you determine whether a person is a candidate for testosterone-replacement treatment?

There are just two ways we determine whether someone has reduced testosterone. One is a blood test and the other one is by characteristic symptoms and signs, and the correlation between those two methods is far from perfect. Normally guys with the lowest testosterone have the most symptoms and men with highest testosterone have the least. However, there are a number of men 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's a reasonable guide. However, no one really agrees on a number. It's similar to 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 is not quite as clear.

*Notice: The Endocrine Society recommends clinical practice guidelines with recommendations click here to find out more for who should and shouldn't receive testosterone therapy. For a complete copy of these instructions, log on to www.endo-society.org.

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

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

The biologically available portion of overall testosterone is called free testosterone, and it is readily available to the cells. Even though it's just a small portion of this total, 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.

Endocrine Society recommendations summarized

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 recommended for men who've

  • Prostate or breast cancer
  • a nodule on the prostate which can be felt during a DRE
  • that a PSA greater than 3 ng/ml without additional evaluation
  • 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 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.. But the data behind this recommendation were drawn from healthy young men. Two recent studies showed little change in blood glucose levels in men 40 and older over the course of this day. One reported no change in typical testosterone till after 2 Between 6 and 2 p.m., it went down by 13%, a modest sum, and probably insufficient to influence diagnosis. Most guidelines nevertheless say it's important to do the test in the morning, however for men 40 and over, it probably doesn't matter much, provided that they obtain their blood drawn before 5 or 6 p.m.

There are some rather interesting findings about dietary supplements. For instance, it seems that those who have a diet low in protein have lower testosterone levels than men who consume more protein. But diet has not been researched thoroughly enough to create any clear recommendations.

Within the following guide, testosterone-replacement therapy refers to the treatment of hypogonadism with exogenous testosterone -- testosterone that is produced outside the body. Based upon the formula, 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.

In a recent prospective study, 36 hypogonadal men took a daily dose of clomiphene citrate for at least three months. Within four to six weeks, all of the men had increased levels of testosteronenone reported any side effects during the year they were followed.

Because clomiphene citrate is not 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'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 only a few choices for men with low testosterone who want to father children.

Formulations

What forms of testosterone-replacement therapy can be found? *

The earliest form is the injection, which we use because it is cheap and since we faithfully get good testosterone levels in nearly everybody. The drawback is that a person should come in every few weeks to get a shot. A roller-coaster effect can also happen as blood glucose levels peak and then return to baseline.

Topical therapies help preserve a more uniform amount of blood glucose. The first form of topical therapy has been a patch, but it has a quite high 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 limits its usage.

The most widely used testosterone preparation from the United States -- and the one I start almost everyone off -- is a topical gel. There are two brands: AndroGel and Testim. 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 degrees in about 80% to 85 percent of guys, but that leaves a significant number who do not absorb sufficient for this to have a positive impact. [For details on various formulations, see table below.]

Are there any downsides to using gels? How much time does it require them to work?

Men who begin using the gels have to come back in to have their own testosterone levels measured again to make certain they are absorbing the right 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 the blood actually goes up quite fast, within a few doses. I normally measure it after two weeks, even though symptoms may not alter for a month or two.

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