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A Harvard Specialist shares his Ideas on testosterone-replacement therapy

It might be stated that testosterone is the thing that makes men, guys. It gives them their characteristic deep voices, big muscles, and facial and body hair, differentiating them from girls. It stimulates the growth of the genitals , plays a role in sperm production, fuels libido, and contributes to regular erections. Additionally, it fosters the production of red blood cells, boosts mood, and assists cognition.

As time passes, the testicular"machinery" that makes testosterone gradually becomes less effective, and testosterone levels begin to drop, by about 1% per year, starting in the 40s. As men get in their 50s, 60s, and beyond, they may begin to have signs and symptoms of low testosterone like lower sex drive 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 functioning and"gonadism" speaking to the testicles). Researchers estimate that the illness affects anywhere from two to six million men in the USA. Yet it's an underdiagnosed problem, with just about 5% of those affected receiving treatment.

Studies have shown that testosterone-replacement therapy may offer a wide range of benefits for men with hypogonadism, including improved libido, mood, cognition, muscle mass, bone density, and red blood cell production. But little consensus exists about what constitutes low testosterone, when testosterone supplementation makes sense, or what risks 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 ailments and male reproductive and sexual problems. He has developed particular expertise in treating lower testosterone levels. In this interview, Dr. Morgentaler shares his perspectives on current controversies, the treatment plans he utilizes his patients, and why he believes specialists should rethink the possible link between testosterone-replacement treatment and prostate cancer.

Symptoms and Continued diagnosis

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

As a urologist, I have a tendency to see men since they have sexual complaints. The primary hallmark of reduced testosterone is low sexual desire or libido, but another may be erectile dysfunction, and some other man who complains of erectile dysfunction must get his testosterone level checked. Men can experience other symptoms, like more difficulty achieving an orgasm, less-intense climaxes, a much lesser quantity of fluid from ejaculation, and a feeling of numbness in the penis when they see or experience something that would normally be arousing.

The more of the symptoms there are, the more probable it is that a man has low testosterone. Many physicians tend to dismiss these"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 guys have when they are treated for benign prostatic hyperplasia, or BPH?

Not exactly. There are a number of drugs that may lessen sex drive, such as the BPH medication 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 treatment for BPH. Erectile dysfunction does not ordinarily go together with it either, though surely if somebody has less sex drive or less attention, it's more of a struggle to have a good erection.

How can you decide whether or not a person is a candidate for testosterone-replacement therapy?

There are two ways that we determine whether someone has reduced 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 ideal. Generally guys with the lowest testosterone have the most symptoms and guys with highest testosterone have the least. However, there are some guys who have reduced levels of testosterone in their blood and have no symptoms.

Looking at the biochemical numbers, The Endocrine Society* believes low testosterone for a entire testosterone level of less than 300 ng/dl, and I believe that's a sensible guide. But no one really agrees on a few. It is not like diabetes, where if your fasting sugar is above a certain level, they will say,"Okay, you've got it." With testosterone, that break point is not quite as apparent.

*Note: The Endocrine Society recommends clinical practice guidelines with recommendations for who should and shouldn't receive testosterone treatment. Watch"Endocrine Society recommendations summarized."

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

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

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

This professional organization recommends testosterone therapy for men who have both

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

Therapy is not Suggested for men who've

  • Prostate or breast cancer
  • a nodule on the prostate that may be felt during a DRE
  • that a PSA greater 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 was to get a testosterone value early in the morning because levels start to fall after 10 or 11 a.m.. But the data behind this recommendation were drawn from healthy young men. Two recent studies demonstrated little change in blood testosterone levels in men 40 and older within the course of the day. One reported no change in typical testosterone until after 2 Between 2 and 6 p.m., it went down by 13 percent, a modest sum, and probably insufficient to affect diagnosis. Most guidelines nevertheless say it's important to do the evaluation in the morning, but for men 40 and over, it likely doesn't matter much, provided that they obtain their blood drawn before 5 or 6 p.m.

There are a number of rather interesting findings about dietary supplements. For instance, it appears that individuals that have a diet low in protein have lower testosterone levels than males who eat more protein. But diet hasn't been researched thoroughly enough to make any recommendations that are clear.

Exogenous vs. endogenous testosterone

Within the following guide, testosterone-replacement therapy refers to the treatment of hypogonadism with adrenal gland -- testosterone that is produced outside the body. Depending on the formula, treatment can cause skin irritation, breast enlargement and tenderness, sleep apnea, acne, reduced sperm count, increased red blood cell count, and additional side effects.

Within four to six weeks, each one the guys had heightened levels of testosteronenone reported some side effects throughout the entire year they had been followed.

Because clomiphene citrate isn't accepted by the FDA for use in males, little information exists regarding the long-term effects of taking it (such as the risk of developing prostate cancer) or whether it's more effective at boosting testosterone compared to exogenous formulas. But unlike exogenous testosterone, clomiphene citrate preserves -- and potentially enriches -- sperm production. That makes drugs such as clomiphene citrate one of just a few choices for men with low testosterone who wish to father children.

Formulations

What kinds of testosterone-replacement treatment are available? *

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

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 large rate of skin irritation. In 1 study, as many as 40 percent of men who used the patch developed a red area on their skin. That limits its use.

The most commonly used testosterone preparation in the United States -- and the one I start almost everyone off -- is a topical gel. According to my experience, it has a tendency to be consumed to great degrees in about 80% to 85 percent of guys, but leaves a substantial number who do not consume sufficient for it to have a positive effect. [For specifics on several different formulations, see table ]

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 certain they are absorbing the right quantity. Our goal is the mid to upper assortment of normal, which usually means around 500 to 600 ng/dl. The concentration of testosterone in blood actually goes up quite quickly, in just several doses. I usually measure it after 2 weeks, though symptoms may not alter for a month or two.

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