When I completed my training in 1988, the state of knowledge about low testosterone and its treatment could be summed up by two comments: "Who cares?" and "Why bother?"

At the time, the medical community believed that testosterone therapy (T therapy) was useful in no more than 5 percent of men with erectile dysfunction. Treatment seemed like a waste of time. Although doctors recognized that low testosterone led to reduced libido, this symptom was considered a problem of older men, making it seem less important to clinicians.

 Fortunately, medical attitudes have changed significantly over the last few years. Today, we know that T therapy can be highly effective for ED treatment. Diminished libido can be a problem for men of all ages, and the health benefits of T therapy may be substantial. Specifically, T therapy can improve body composition and bone density, correct anemia and resolve multiple symptoms, including chronic fatigue and depression.¹ 

In fact, evidence from several sources shows that men with normal T levels live longer than men with low T, suggesting the possibility that T therapy may lead to greater longevity.^2,3

Men and Lizards

Shortly after I began my medical practice, I realized that T therapy had important effects for men. Despite my training that diagnosing low T was unimportant, I was still curious about testosterone based on research I had performed earlier as an undergraduate at Harvard College. For three years, I had worked in a laboratory under the direction of biologist David Crews, who is now at the University of Texas at Austin. Together, we investigated the effects of hormones, such as testosterone, on the behavior of male lizards. What we found was that testosterone appeared to have powerful influences on sexual function in the lizards.⁴ So I began testing for testosterone levels in men with ED and was surprised to find that many of these men had low T concentrations.

However, it was the response of men to T therapy that really fascinated me. The first surprise was that many men responded well to T therapy for their erection problems. Even more interesting was hearing how T therapy helped many of them feel more energetic, more upbeat and more "alive."

Yet, I was still skeptical and well aware of the possibility that a placebo might be responsible for these reactions. So what convinced me that the beneficial effects of T therapy were real? At the time, the only form of T therapy was intramuscular injections. Back then, men received an injection every three to four weeks.

When I asked my patients what they noticed with their T injections, many of them would say a version of the following: "I feel great for the first week or two after the injection, but afterwards, I feel lousy again, as if I had never received an injection in the first place." These men didn't know it, but T levels tend to drop back to baseline low levels within 12 to 14 days. And the lousy feelings they experienced before the next injection accurately reflected low T levels. It became clear to me that men could tell when their T levels were normal and when they were low.

Given this, the time between injections has been shortened to one to two weeks to reduce the likelihood that T levels will drop below the normal range.

Health Benefits of T Therapy

I'm convinced that we're on the cusp of determining that normal testosterone is important for the health of men of all ages. For many years, medical researchers have focused on sexual symptoms, but they're now looking at testosterone as being a key player in body composition, diabetes, cardiovascular health and bone health.

For example, men with T levels in the lower quarter of the population have double the risk of developing diabetes later in life compared with men with higher T levels. These men also are at increased risk for developing metabolic syndrome--a constellation of problems that includes high blood pressure, high blood sugar, obesity and high lipid concentrations--which confers an increased risk of heart disease. Low T contributes to low bone density in men, which increases the risk of fractures occurring from minor injuries.

Men usually come to see me for sexual problems. In many men, a contributing cause is low T, which can cause weak erections, diminished sex drive, reduced feeling in the penis, more difficulty achieving an orgasm and reduced orgasm intensity. Other symptoms of low T include reduced energy, feeling "blah" or blue, poor motivation, and worse physical performance, such as with exercise or athletics.

Sexual Benefits of T therapy

How good is T therapy for sexual symptoms? From our own published studies and those of others, approximately 80 percent of men will experience an increase in libido, and two-thirds will notice improved erections.⁵ One interesting study took a group of men with low T who were unable to have adequate erections despite full-dose Viagra. After T therapy normalized testosterone levels, the men were instructed to attempt intercourse without Viagra. If there was no success, men were allowed to try Viagra again.

By the end of the study, one-third of the men were able to have sex with T therapy alone, another third was successful with the combination of T therapy and Viagra, and the remaining third were still unable to achieve adequate erections.⁶ This study suggests that T therapy may be better than Viagra for some men with ED. It also may rescue adequate erections in other men for whom the ED pills haven't worked.

Within three months, our tests show that most of the men gain muscle and lose fat-an interesting beneficial side effect of T therapy. Positivity begets positivity, and I remain enormously gratified that so many of patients move forward with long-deferred projects once they begin T therapy. Many tell me their relationships have improved and that their production at work has increased.

But let me be clear: Not everyone with low T responds to T therapy. T therapy is only for men with a true testosterone deficiency. I can't emphasize this point enough. The goal of treatment is to normalize the concentration of a naturally occurring hormone to youthful levels. It is not to try to benefit men with supraphysiologic doses, whatever those effects may be. In addition, if a man does not respond adequately to T therapy within three months, I tend to discontinue treatment at that time and search for other causes or treatment strategies. For ED, this will usually mean a trial of the oral ED medications. For mood and diminished sense of vitality, I need to consider depression, stress, interpersonal relationships and thyroid disorders, among others.  

Risks of T Therapy

A big obstacle to finding a physician willing to prescribe T therapy is the belief that raising testosterone might increase the risk of prostate cancer. This topic has been a particular focus of my research, and I'm pleased to report that this issue has been largely laid to rest.^7,8 A landmark study published this year looked at the effect of testosterone and other hormones on the risk of developing prostate cancer over time in a large group of men.⁹

The results showed definitively that there was no difference in testosterone values between men with cancer and without cancer. It also showed that men with high testosterone levels were at no greater risk than men with low testosterone.

Nonetheless, all medical treatments are associated with some risk. For T therapy, the risks include an elevation of the red blood cell count, tenderness or swelling of the breast area (rare, but goes away when the treatment is stopped), acne (rare), reduced sperm production and fluid retention (rare). The main contraindication to T therapy is a prior history of prostate cancer, but even this old prohibition appears to be falling by the wayside. I recently published a report about an 84-year-old man with untreated prostate cancer who had two years of T therapy. No cancer progression occurred.¹⁰

If a man has symptoms of low T, such as sexual problems, fatigue, or loss of muscle mass or strength, order a blood test. The traditional test is called total testosterone, and values below 350 ng/dl are consistent with low T. However, another test, called free testosterone, is even more useful than total testosterone. Values less than 1.5 ng/dl (or 15 pg/ml--different labs use different units) also indicate low T.

If either the total or free T is low, a three-month trial of T therapy may make sense to see if symptoms improve. In general, if a man does not experience any benefits in three months, I will discontinue treatment.

Treatment Options

If a diagnosis of low T is made, we can pursue several options. Unfortunately, there is no effective and safe pill. Some old oral formulations are still available, but they're not effective in raising testosterone. They're also associated with significant liver toxicity, so they're almost never used.

Instead, the most common treatment in the United States is a gel, which is rubbed daily into the upper arms, shoulders and chest. Injections are another option. They're usually given in the buttocks and are highly effective, but require treatment every week or two. This treatment is less commonly used, less expensive and produces good levels of testosterone more consistently than gels; it remains an important mode of treatment.

Patches are applied daily, but can cause considerable skin irritation. For this reason, they've been largely replaced by the gels. A relatively new option is placing extended-release pellets under the skin, providing good testosterone levels for three to six months. I've had good success with these pellets, called Testopel, and many men appreciate the fact that they don't have to apply the gel daily.

On the horizon is a long-acting injection that may require only five injections per year. The product is available in Europe and many other countries; it may become available for use in the United States later this year.

Finally, a pellet can be applied to the gum line, above the teeth. This works well but must be changed twice daily. This is the least commonly used form of treatment, but I do have patients who like this quite well.

Medical research shows that normal levels of testosterone play an important role in our health. The research also shows that low T can be associated with several sexual and nonsexual symptoms that are highly treatable with T therapy. I'm a strong believer that T therapy can provide many important health benefits for men with low T. With appropriate medical monitoring--laboratory tests for hematocrit or hemoglobin and PSA, as well as a digital rectal examination of the prostate--T therapy is safe and effective. I recommend two to three visits in the first year, with a yearly visit thereafter.

Normalizing testosterone can help men lead full, loving and satisfying lives. I've seen this in my practice repeatedly, and it's one of the most rewarding aspects of my work as a physician.

References

1. Bhasin S, Cunningham GR, Hayes FJ, Matsumoto AM, Snyder PJ, Swerdloff RS, Montori VM. Testosterone therapy in adult men with androgen deficiency syndromes: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2006; 91:1995-2010.

2. Shores MM, Matsumoto AM, Sloan KL, Kivlahan DR. Low serum testosterone and mortality in male veterans. Arch Intern Med. 2006;166(15):1660-5.    

3. Laughlin GA, Barrett-Connor E, Bergstrom J.  Low serum testosterone and mortality in older men. J Clin Endocrinol Metab. 2008;93(1):68-75.

4. Morgantaler A, Crews D. Role of the anterior hypothalamus-preoptic area in the regulation of reproductive behavior in the lizard, Anolis carolinensis: implantation studies. Horm Behav. 1978;11(1):61-73.

5. Reyes-Vallejo L, Lazarou S, Morgentaler A. Subjective sexual response to testosterone replacement therapy based on initial serum levels of total testosterone. J Sexual Med 4:1757-62,  2007.

6. Hwang TI, Chen HE, Tsai TF, Lin YC. Combined use of androgen and sildenafil for hypogonadal patients unresponsive to sildenafil alone. Int J Impot Res. 2006;18(4):400-4.

7. Morgentaler A. Testosterone and Prostate Cancer: An Historical Perspective On A Modern Myth. Eur Urology, 50:935-9, 2006.

8. Morgentaler A, Traish AM. Shifting the Paradigm of Testosterone and Prostate Cancer: The Saturation Model and the Limits of Androgen-Dependent Growth. Euro Urol, epub Sept 24, 2008.

9. Endogenous Hormones Prostate Cancer Collaborative Group, Roddam AW, Allen NE, Appleby P, Key TJ. Endogenous sex hormones and prostate cancer: a collaborative analysis of 18 prospective studies. JNCI 2008; 100:170-83.

10. Morgentaler A. Two years of testosterone therapy associated with decline in prostate-specific antigen in a man with untreated prostate cancer. J Sex Med. 2009;6(2):574-7.

Abraham Morgentaler, MD, is an associate clinical professor of urology at Harvard Medical School and the founder of Men's Health Boston, a center focusing on sexual and reproductive health for men. He is the author of Testosterone for Life (McGraw-Hill, 2008), the first book about low testosterone by a prominent researcher in the field. The culmination of 30 years of research, it explains every aspect of this common medical condition and its treatment. Dr. Morgentaler is also the author of The Viagra Myth and The Male Body.

Disclosure: Dr. Morgentaler indicates that he's a consultant for Slate and Indevus. He also receives research grants and honoraria from Slate, Indevus, Watson, Solvay and Auxilium.