A Harvard expert 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 guys, men. It gives them their characteristic deep voices, big muscles, and body and facial hair, distinguishing them from women. It stimulates the development of the genitals at puberty, plays a role in sperm production, fuels libido, and leads to regular erections. Additionally, it boosts the production of red blood cells, boosts mood, and aids cognition.
Over time, the testicular"machinery" which makes testosterone slowly becomes less powerful, and testosterone levels begin to fall, by approximately 1% per year, beginning in the 40s. As men get in their 50s, 60s, and beyond, they may begin to have symptoms and signs of low testosterone such as reduced sex drive and sense of energy, erectile dysfunction, decreased energy, reduced muscle mass and bone density, and anemia. Taken together, these signs and symptoms are often called hypogonadism ("hypo" significance low working and"gonadism" referring to the testicles). Yet it is an underdiagnosed issue, with only about 5% of those affected receiving treatment.
But little consensus exists on what constitutes low testosterone, when testosterone supplementation makes sense, or what dangers patients face.
He has developed specific expertise in treating low testosterone levels. In this interview, Dr. Morgentaler shares his perspectives on current controversies, the treatment plans he utilizes his own patients, and he believes specialists should rethink the potential link between testosterone-replacement therapy and prostate cancer.
Symptoms and diagnosisWhat symptoms and signs of low testosterone prompt that the typical man to find a doctor?
As a urologist, I tend to see guys because they have sexual complaints. The main hallmark of reduced testosterone is reduced sexual desire or libido, but another can be erectile dysfunction, and some other guy who complains of erectile dysfunction must possess his testosterone level checked. Men may experience other symptoms, like more difficulty achieving an orgasm, less-intense climaxes, a much smaller quantity of fluid out of ejaculation, and a feeling of numbness in the penis when they see or experience something that would usually 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 those"soft symptoms" as a normal part of aging, but they are often treatable and reversible by decreasing testosterone levels.
Are not those the very same symptoms that guys have when they're treated for benign prostatic hyperplasia, or BPH?
Not precisely. There are quite a few drugs that 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 doesn't go together with therapy for BPH. Erectile dysfunction does not ordinarily go along with it either, though certainly if a person has less sex drive or less attention, it's more of a challenge to have a good erection.
How do you decide whether or not a person is a candidate for testosterone-replacement therapy?
There are two ways we determine whether somebody has reduced testosterone. One is a blood test and the other is by characteristic symptoms and signs, and the correlation between these two approaches is far from ideal. Normally guys with the lowest testosterone have the most symptoms and guys with highest testosterone have the least. But there are a number of men who have reduced levels of testosterone in their blood and have no symptoms.
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. However, no one quite agrees on a number. It's not like diabetes, where if your fasting sugar is over 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 see it here shouldn't receive testosterone therapy. For a complete copy of the our website instructions, log on to www.endo-society.org. |
Is complete testosterone the ideal thing to be measuring? Or if we are measuring something different?
This is just another area of confusion and good debate, but I do not think it's as confusing as it appears to be from the literature. When most doctors learned about testosterone in medical school, they learned about overall testosterone, or all the testosterone in the human body. However, about half of their testosterone that's circulating in the bloodstream is not available to the cells.
The available part of total testosterone is called free testosterone, and it is readily available to the cells. Nearly every lab has a blood test to measure free testosterone. Even though it's only a small portion of the total, the free testosterone level is a fairly good indicator of low testosterone. It's not ideal, but the correlation is greater than with total testosterone.
This professional organization recommends testosterone treatment for men who have
Therapy Isn't Suggested for men who've
- Breast or prostate cancer
- a nodule on the prostate that can be felt during a DRE
- a PSA greater than 3 ng/ml without further evaluation
- a hematocrit greater than 50 percent or thick, viscous blood
- untreated obstructive sleep apnea
- severe lower urinary tract symptoms
- class III or IV heart failure.
Do time of day, diet, or other factors 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.. However, the information behind that recommendation were attracted to healthy young men. Two recent studies showed 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 modest 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 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 men who consume more protein. But diet has not been studied thoroughly enough to make any recommendations that are clear.
FormulationsExogenous vs. endogenous testosterone
In this article, testosterone-replacement therapy refers to the treatment of hypogonadism with adrenal gland -- testosterone that's produced outside the body. Depending upon the formulation, treatment can cause skin irritation, breast tenderness and enlargement, sleep apnea, acne, reduced sperm count, increased red blood cell count, and other side effects.
Preliminary research has proven that clomiphene citrate (Clomid), a drug generally prescribed to stimulate ovulation in women struggling with infertility, can boost the creation of natural testosterone, also known as endogenous testosterone, in men. In 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 of the guys had heightened levels of testosteronenone reported some side effects during the entire year they had been followed.
Since clomiphene citrate is not accepted by the FDA for use in men, little information exists about the long-term ramifications of taking it (including the probability of developing prostate cancer) or if it is more capable of boosting testosterone than exogenous formulas. But unlike exogenous testosterone, clomiphene citrate maintains -- and potentially enriches -- sperm production. This makes medication like clomiphene citrate one of just a few choices for men with low testosterone who want to father children.
What kinds of testosterone-replacement treatment can be found? *
The oldest form is an injection, which we use because it's inexpensive and since we reliably become fantastic testosterone levels in almost everybody. The disadvantage is that a man needs to come in every few weeks to get a shot. A roller-coaster effect can also occur as blood testosterone levels peak and return to research. [See"Exogenous vs. endogenous testosterone," above.]
Topical therapies help maintain a more uniform level of blood glucose. The first kind of topical treatment was a patch, but it has a quite large rate of skin irritation. In 1 study, as many as 40% of people that used the patch developed a reddish area on their skin. That limits its usage.
The most commonly used testosterone preparation in the United States -- and the one I begin almost everyone off -- is a topical gel. There are just two brands: AndroGel and Testim. According to my experience, it tends to be absorbed to good degrees in about 80% to 85% of guys, but that leaves a substantial number who do not absorb sufficient for it to have a positive effect. [For specifics on various formulations, see table below.]
Are there any downsides to using dyes? How long does it take for them to work?
Men who begin using the implants need to come back in to have their testosterone levels measured again to make certain they're absorbing the proper quantity. Our goal is the mid to upper range of normal, which usually means around 500 to 600 ng/dl. The concentration of testosterone in blood really goes up quite quickly, within several doses. I usually measure it after 2 weeks, even though symptoms may not change for a month or two.