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A Harvard expert shares his Ideas on testosterone-replacement therapy

An interview with Abraham Morgentaler, M.D.

It might be said that testosterone is the thing that makes men, men. It gives them their characteristic deep voices, big muscles, and facial and body hair, differentiating them from women. It stimulates the development of the genitals at puberty, plays a role in sperm production, fuels libido, and leads to normal erections. Additionally, it boosts the production of red blood cells, boosts mood, and assists cognition.

Over time, the testicular"machinery" which makes testosterone slowly becomes less powerful, and testosterone levels start to drop, by approximately 1% per year, beginning in the 40s. As men get in their 50s, 60s, and beyond, they may start to have symptoms and signs of low testosterone like lower libido and sense of energy, erectile dysfunction, decreased energy, decreased muscle mass and bone density, and nausea. Taken together, these signs and symptoms are often referred to as hypogonadism ("hypo" meaning low functioning and"gonadism" speaking to the testicles). Researchers estimate that the condition affects anywhere from two to six million men in the USA. Yet it's an underdiagnosed problem, with only about 5 percent of these affected receiving treatment.

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 specific experience in treating lower testosterone levels. In this interview, Dr. Morgentaler shares his perspectives on current controversies, the treatment plans he utilizes his own patients, and why he thinks specialists should rethink the potential connection between testosterone-replacement therapy and prostate cancer.

Symptoms and diagnosis

What signs and symptoms of low testosterone prompt the average person to find a physician?

As a urologist, I have a tendency to see men because they have sexual complaints. The primary hallmark of low testosterone is low 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're often treatable and reversible by decreasing testosterone levels.

Are not 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 amount of the ejaculatory fluid, no wonder. However a decrease in orgasm intensity normally doesn't go together with therapy for BPH. Erectile dysfunction does not ordinarily go together with it either, though certainly if somebody has less sex drive or less interest, it's more of a challenge to get a good erection.

How can you decide if or not a person is a candidate for testosterone-replacement treatment?

There are two ways that we determine whether somebody has low testosterone. One is a blood test and the other 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. But there are a number of guys who have reduced levels of testosterone in their blood and have no symptoms.

Looking purely at the biochemical amounts, The Endocrine Society* believes low testosterone for a total testosterone level of less than 300 ng/dl, and I think that's a sensible guide. However, no one quite agrees on a number. It's not like diabetes, where if your fasting sugar is over 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 publishes clinical practice guidelines with recommendations for who should and shouldn't receive testosterone therapy. For a complete copy of these instructions, i thought about this log on to www.endo-society.org.

Is total testosterone the ideal thing to be measuring? Or should we be measuring something different?

This is another area of confusion and great 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 overall testosterone, or all the testosterone in the human body. But about half of their testosterone that is circulating in the bloodstream isn't available to cells. It's tightly 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 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

Therapy is not Suggested for men who've

  • Prostate or breast cancer
  • a nodule on the prostate which can be felt during a DRE
  • that a PSA higher than 3 ng/ml without further analysis
  • 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 elements affect testosterone levels?

    For many years, the recommendation has been 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 mature over the course of this day. One reported no change in typical testosterone till after 2 Between 2 and 6 p.m., it went down by 13%, a small sum, and probably not enough to affect diagnosis. Most guidelines still say it's important to perform the evaluation in the morning, however for men 40 and above, it likely doesn't matter much, provided that they obtain their blood drawn before 6 or 5 p.m.

    There are some very interesting findings about dietary supplements. By way of example, 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 therapy refers to the treatment of hypogonadism with adrenal gland -- testosterone that's produced outside the body. Based on the formulation, treatment can cause skin irritation, breast tenderness and enlargement, sleep apnea, acne, decreased 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 three or more months. Within four to six months, each one the guys had increased levels of testosteronenone reported some side effects throughout the entire year they had been followed.

    Since clomiphene citrate isn't 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 is more effective at boosting testosterone than exogenous formulations. But unlike exogenous testosterone, clomiphene citrate preserves -- 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 kinds of testosterone-replacement treatment can be found? *

    The earliest form is an injection, which we still use because it's cheap and since we faithfully become fantastic 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 happen as blood testosterone levels peak and then return to research.

    Topical treatments help maintain a more uniform level of blood testosterone. The first kind of topical treatment was a patch, but it has a very high rate of skin irritation. In 1 study, as many as 40 percent of men who used the patch developed a red area in their skin. That restricts its usage.

    The most widely used testosterone preparation from 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 consume sufficient for it to have a favorable impact. [For specifics on several different formulations, see table ]

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

    Men who begin using the gels have to return in to have their testosterone levels measured again to be sure they are absorbing the proper amount. Our goal is the mid to upper assortment of normal, which generally means around 500 to 600 ng/dl. The concentration of testosterone in blood actually goes up quite fast, within several doses. I usually measure it after 2 weeks, although symptoms may not alter for a month or two.

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