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A Harvard Specialist shares his thoughts on testosterone-replacement therapy

A meeting with Abraham Morgentaler, M.D.

It might be said that testosterone is what makes guys, guys. It gives them their characteristic deep voices, large muscles, and facial and body hair, differentiating them from girls. It stimulates the growth of the genitals at puberty, plays a role in sperm production, fuels libido, and leads to normal erections. It also boosts the creation of red blood cells, boosts mood, and aids cognition.

As time passes, the "machinery" which makes testosterone slowly 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 may 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 symptoms and signs are often referred to as hypogonadism ("hypo" meaning low working 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 shown that testosterone-replacement therapy can offer a vast selection of benefits 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 can 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 sexual and reproductive problems. He has developed particular experience in treating low testosterone levels. In this interview, Dr. Morgentaler shares his views on current controversies, the treatment strategies he utilizes his own patients, and he thinks experts should reconsider the potential link between testosterone-replacement treatment and prostate cancer.

Symptoms and diagnosis

What signs and symptoms of low testosterone prompt that the typical man to find 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 can be erectile dysfunction, and any man who complains of erectile dysfunction must get his testosterone level checked. Men can experience different symptoms, such as more trouble achieving an orgasm, less-intense orgasms, a much lesser amount of fluid from ejaculation, and a sense of numbness in the penis 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 these"soft symptoms" as a normal part of aging, but they're often treatable and reversible by normalizing testosterone levels.

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

Not precisely. There are a number of drugs that may reduce libido, such as the BPH drugs finasteride (Proscar) and dutasteride (Avodart). Those drugs can also reduce the quantity of the ejaculatory fluid, no wonder. But a reduction in orgasm intensity normally doesn't go along with treatment for BPH. Erectile dysfunction does not ordinarily go together with it either, though certainly if a person has less sex drive or less attention, it is more of a challenge to get a fantastic 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 is by characteristic signs and symptoms, and the correlation between these two approaches is far from ideal. Normally guys with the lowest testosterone have the most symptoms and men with highest testosterone have the least. But there are some men who have reduced levels of testosterone in their blood and have no signs.

Looking 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, in which if your fasting sugar is over a certain level, they will say,"Okay, you've got it." With testosterone, that break point isn't quite as apparent.

*Notice: The Endocrine Society recommends clinical practice guidelines with recommendations for who should and should not receive testosterone treatment. Watch"Endocrine Society recommendations summarized."

Is total testosterone the right thing to be measuring? Or should we be measuring something else?

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

The available part of total testosterone is called free testosterone, and it's readily available to the cells. Though it's just a little fraction of the total, the free testosterone level is a pretty good indicator of reduced testosterone. It is not ideal, but the significance is greater compared to testosterone.

This professional organization recommends testosterone treatment for men who have

Therapy Isn't Suggested for men who have

  • Prostate or breast cancer
  • a nodule on the prostate which may be felt during a DRE
  • that a PSA greater 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 symptoms
  • class III linked here or IV heart next failure.

    Do time daily, diet, or other elements affect testosterone levels?

    For years, the recommendation was to receive a testosterone value early in the morning because levels start to fall after 10 or 11 a.m.. However, 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 average testosterone till after 2 p.m. Between 6 and 2 p.m., it went down by 13 percent, a modest sum, and probably not enough to affect identification. Most guidelines still say it is important to do the evaluation in the morning, but for men 40 and over, it probably does not matter much, provided that they get their blood drawn before 6 or 5 p.m.

    There are some rather interesting findings about diet. By way of example, it seems that individuals that have a diet low in protein have lower testosterone levels than males who consume more protein. But diet has not been researched thoroughly enough to create any clear recommendations.

    Exogenous vs. endogenous testosterone

    In the following article, testosterone-replacement treatment refers to the treatment of hypogonadism with exogenous testosterone -- testosterone that's manufactured outside the body. Based on the formula, treatment can lead to skin irritation, breast enlargement and tenderness, sleep apnea, acne, decreased sperm count, increased red blood cell count, and additional side effects.

    Preliminary research has proven that clomiphene citrate (Clomid), a drug generally prescribed to stimulate ovulation in women struggling with infertility, can foster the creation of natural testosterone, known as endogenous testosterone, in men. 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 of the guys had increased levels of testosterone; none reported some side effects during the entire year they had been followed.

    Because clomiphene citrate isn't approved by the FDA for use in men, little information exists regarding the long-term effects of carrying it (including the probability of developing prostate cancer) or whether it is more capable of boosting testosterone than exogenous formulations. But unlike adrenal gland, clomiphene citrate maintains -- and possibly enriches -- sperm production. This makes drugs such as clomiphene citrate one of only a few choices for men with low testosterone that want to father children.

    What forms of testosterone-replacement treatment are available? *

    The earliest form is the injection, which we still use because it is cheap and since we reliably get fantastic testosterone levels in almost everybody. The disadvantage is that a man should come in every couple of weeks to get a shot. A roller-coaster effect can also occur as blood glucose levels peak and return to baseline.

    Topical therapies help maintain a more uniform level of blood glucose. The first kind of topical therapy was a patch, but it has a very high rate of skin irritation. In 1 study, as many as 40 percent of people that used the patch developed a reddish area in their skin. That limits its use.

    The most commonly used testosterone preparation in the United States -- and also the one I begin almost everyone off -- is a topical gel. There are just two brands: AndroGel and Testim. The gel comes from tiny tubes or within a unique dispenser, and you rub it on your shoulders or upper arms once a day. According to my experience, it has a tendency to be consumed to good levels in about 80% to 85% of men, but that leaves a substantial number who do not consume sufficient for it to have a positive effect. [For specifics on various formulations, see table below.]

    Are there any drawbacks to using gels? How much time does it require them to get the job done?

    Men who begin using the gels have to come back in to have their testosterone levels measured again to make 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 actually goes up quite quickly, within a few doses. I usually measure it after two weeks, though symptoms may not change for a month or two.

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