Testosterone and Men's Health: New Insights
Today's aging man might want to consultant an endocrinologist to address his urogenital concerns.
By Richard F. Spark, MD, FACE

Today's man—especially the mature man—is under assault. Each night as he tunes into the evening news or his favorite TV sports event he cannot escape the relentless attack on his masculinity. One after another prime time advertiser reminds him that he is no longer as young as he once was and that he spends too much time in the bathroom trying to urinate and too little time in the bedroom having sex.

He is encouraged to "speak with your doctor." But which doctor should he speak to about these problems? Both urination and the ability to have sexual intercourse require normal male genital function. In the past his urologist, someone familiar with male genital anatomy, may have been consulted to help him cope with these problems. Today, however, he might want to chat with his endocrinologist who has a better understanding of the male sexual chemistry needed to allow a man to urinate effortlessly and acquire and maintain penile erections firm enough to allow him to have and enjoy sexual intercourse.

The hormone testosterone plays a critical role in a man's problems with urination and sexual function as he ages. With advancing years the testosterone made in a man's testicles enters his blood stream and then penetrates his prostate gland. There, under the influence of the enzyme 5-alpha reductase, testosterone is transformed into the hormone dihydrotestosterone (DHT) and it is the increasing level of intraprostatic DHT that is the culprit responsible for the age-related increase in the size of a man's prostate.

A man's prostate gland is anatomically positioned right next to his urethra. Pressure from the bulging prostate on the urethra causes a blockage impeding the flow of urine making it difficult for a man to release all the urine stored in his bladder. He is left with a sensation of fullness as well as a need to urinate more often. Years ago prostate surgery to whittle down the size of the prostate was the only way to alleviate pressure on the bladder so that urine could flow more freely.

Now that we know that the hormone DHT is directly responsible for prostate growth there are other options. Some men have low DHT levels because they are born without the enzyme needed to transform testosterone to DHT. These men have tiny prostate glands that never enlarge. To mimic this experiment of nature, two medications, finasteride (Proscar, Merck) and duasteride (Avodart, GlaxoSmithKline), have been developed. Both medications block the conversion of testosterone to DHT and short-circuit the stimulus to prostate growth. Treatment with either medication brings about a decline in the amount of DHT stored in the prostate. As DHT levels within the prostate decline the prostate becomes smaller and no longer impinges on the urethra, allowing men to urinate more freely.

TESTOSTERONE AND SEXUAL FUNCTION IN YOUNG AND NOT-SO-YOUNG MEN
There is a time in every man's life coinciding with the teenage surge in testosterone release into his blood stream when he wakes every morning with an erection and quite suddenly starts to experience sexual feelings. The morning erections are due to a diversion of blood flow into specialized spongy tissue in his penis, the corpora cavernosae. As the pressure within these areas increases his penis swells and then becomes rigid enabling him to have sexual intercourse.

As a young man the flow of blood into his penis is free and uninterrupted so that he can experience an erection without difficulty. His interest in sex (libido) is, however, testosterone dependent. As long as blood flows freely in his body he can experience erections and as long as his testicles churn out a full quotient of testosterone, interest in sex is sustained.

Unfortunately, over time as a man gets older he may acquire new habits and problems that disrupt both his natural sexual energy and sexual potency. He does not always eat properly, he exercises less, starts to put on weight, and becomes prone to the development of diabetes and high cholesterol. He takes up and cannot abandon the habit of smoking cigarettes. All of these behaviors individually and collectively start damaging blood vessels in his body, limiting the flow of blood to his vital organs. If blood flow though his coronary arteries is diminished, he has angina, whereas claudication is the natural consequence of diminished blood flow to his lower extremities.

An inability to acquire or maintain an erection is inevitable if blood flow to the penis is compromised. Fortunately there are now three different medications, sildenafil (Viagra, Pfizer), vardenafil (Levitra, Bayer Pharmaceuticals Corporation with GlaxoSmithKline and Schering Corporation), and tadalafil (Cialis, Elil Lilly and Company), to help with this problem. All increase blood flow to the erectile chamber of the penis and improve a man's chance of acquiring and maintaining an erection in response to sexual stimulation. These agents were thought to be the only medication that men with erectile dysfunction would need to become sexually potent again. Unfortunately, none of these medications are always effective for all men. Some men fail to benefit from these medications because, in addition to low blood flow, they also have low serum testosterone levels.

In the original studies of sildenafil, vardenafil, and tadalafil, men with low testosterone levels were not allowed to participate. We now know why. It turns out that an enzyme within the penis, nitric oxide synthase (NOS), must be present in ample amounts for all of these erection enhancers to work. Men with low testosterone levels have low NOS levels, and that is why they do not have erections after using sildenafil, vardenafil, or tadalafil. Testosterone treatment normalizes testosterone levels and once this occurs men can once again experience erections when they use any of the above mentioned agents.

TESTOSTERONE AND MENTAL HEALTH
Not only is the maintenance of a normal testosterone level vital for a man's sexual health, it now appears to be critical for his emotional health and possibly his longevity as well. Recent studies indicate that men experiencing depression do not respond equally to antidepressant medication. Some men, especially those with low testosterone levels, remain depressed until testosterone treatment is added to their antidepressant medication.

TESTOSTERONE AND LONGEVITY
Surprisingly there are other risks for men with testosterone deficiency. Men with low testosterone levels do not live as long as men with normal testosterone levels. In one study 794 men had serum testosterone levels measured and then followed for 11.8 years. Those with the lowest serum testosterone level (≤241 ng/dL; 280–800 ng/dL is the normal male testosterone range) were more likely to have died during those 11.8 years than age-matched men with normal testosterone levels.

TESTOSTERONE AND THE ANNUAL PHYSICAL
Today, men show up for their annual physical and can expect to have measurements of height, weight, blood pressure, A1C to check for diabetes (one out of every three men with age-related diabetes has low testosterone levels), as well as a cholesterol screen. Considering the importance of testosterone to a man's sexual and emotional health as well as his longevity, perhaps it is now time for serum testosterone measurements to be included as part of the routine annual physical for all men.

This article also appears in the American Association of Clinical Endocrinologists' Power of Prevention Spring issue.

Richard F. Spark, MD, FACE, is Associate Clinical Professor of Medicine at Harvard Medical School and Director of the Steroid Research Lab at Boston's Beth Israel Deaconess Medical Center. Dr. Spark is a member of the Review of Endocrinology Editorial Board. He may be reached at rspark@bidmc.harvard.edu.