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Abraham Morgentaler, MD, FACS Testosterone Therapy for Life

June 2010

FDA-approved Drugs Fail to Prevent Heart Attack and Stroke

Millions of men needlessly suffer from low sex drive, loss of energy, and diminished enthusiasm for life—because of low levels of the male hormone testosterone. Normal levels can be readily restored using simple testosterone replacement therapy (TRT)—but in many audiences, those very words evoke the responses we commonly attribute to the hormone itself: rage, aggression, impulsiveness, and territoriality! Most physicians and many lay people continue to labor under a host of misconceptions, both about testosterone’s effects on human biology and behavior, and about the role of testosterone therapy in older adults.

The truth is finally emerging, however, thanks largely to the efforts of Dr. Abraham Morgentaler of the Harvard Medical School, and a small number of equally dedicated clinician-scientists who have devoted their careers to understanding testosterone’s myriad effects on humans throughout the life span, and on building a fact-based, myth-busting approach to TRT, thus revealing its benefits and its risks.

We recently had the opportunity to interview Dr. Morgentaler at length about his latest book, Testosterone for Life (McGraw-Hill, 2008),1 and about the exciting breakthroughs in men’s health and medicine for older adults in which he has participated. Morgentaler is no newcomer to this field—he’s a practicing urologist, an Associate Clinical Professor of Urology at the Harvard Medical School and the founder of Men’s Health Boston (a center focusing on sexual and reproductive health for men). The author of a number of books including The Male Body (Fireside, 1993) and The Viagra Myth (Jossey-Bass, 2003), Morgentaler has been working in men’s health, and particularly on the impact of testosterone, since he was an undergraduate student 30 years ago.

It’s unusual for undergraduates to publish as a first author, especially in the field that turns out to be their life’s work—so we asked Dr. Morgentaler to take us back to 1978 and his original study in the journal Hormones and Behavior.2 Morgentaler laughed—“We were actually studying lizards, which have very elaborate and ritualized mating behaviors,” he recalled. “We were just beginning to learn about the powerful effects of testosterone on specific regions of the brain, and how it influences behavior.” To that end, Morgentaler and his mentor, Dr. David Crews, were working with lizards that had been castrated to remove any source of native testosterone. “Castration completely eliminated the mating displays in male lizards,” Morgentaler noted. “They were simply oblivious to females in their presence.”

But when Crews and Morgentaler implanted testosterone in a very primitive brain center called the pre-optic area, the mating ritual was restored completely!2 “What was particularly remarkable about this,” Morgentaler continued, “was that these effects were purely local—we didn’t see any increase in blood testosterone levels. This showed us that testosterone has very precise, very specific effects on highly complex behaviors that originate deep in the brain.” The pre-optic area is responsible for many aspects of reproductive behavior in humans as well,3 and in fact the interaction of testosterone with the brain is a fundamental fact throughout the animal kingdom. Intrigued by all this, Dr. Morgentaler set out on a lifetime of discovery. Let’s be “armchair travelers” on the high points of his journey.

Testosterone and Aging: Why Should We Care?

Testosterone and Aging: Why Should We Care?

“The first question to be asked in thinking about testosterone in humans is ‘Why should we care?’” Morgentaler began. “Among men more than 45-50 years old, the prevalence of low testosterone is at least 20-30%,” he continued (that’s an estimated 2 to 4 million men in the US alone!).4 “Many people (highly-respected physicians among them) have long believed that levels decline as a natural consequence of advancing age,5,6 and that therefore there is nothing we can or should do about it,” he went on. “That’s like telling a middle-aged person that since vision typically deteriorates with age, there’s no point in prescribing glasses—or that we shouldn’t treat atherosclerosis to prevent heart attacks, because it too is an age-related phenomenon. It just doesn’t make sense!”

How can a man know if he has low testosterone levels (or as Dr. Morgentaler calls it, “Low T”)? “Not every man with low T will have symptoms,” Morgentaler responded, “though many people with symptoms aren’t aware that they have low T. Because of their lack of understanding of the problem, compounded by some genuinely erroneous data that have been misquoted or overstated for decades, most doctors don’t regularly check testosterone levels—so many men go on suffering, undiagnosed.”

“In my practice, of course I see men whose complaints are primarily sexual: diminished drive and interest in sex, but also poor performance and absent or unsatisfying orgasms.” But low T also affects mood and behavior outside the bedroom. “I also find a very large number of men whose complaints are non-sexual in nature: they have chronic fatigue, they feel tired, lack energy and focus; they seem to have lost much of the drive that made them the men they thought they were (and liked to be).” As one of Dr. Morgentaler’s patients put it eloquently, “it feels like I have ‘brain fog’ all the time.”

Physical performance can suffer as well. Many patients complain that it takes much longer to “recharge” after exertion. “They tell me they just feel dead after what was once a normal workout,” Morgentaler reports, “or they say that they just can’t seem to improve with progressive training. That makes a lot of sense since we know that reduced testosterone levels contribute to loss of muscle bulk and strength, as well as to increased fat stores.”5,7

Millions of men needlessly suffer from low sex drive, loss of energy, and diminished enthusiasm for life—because of low levels of the male hormone testosterone.

It isn’t just the men themselves who perceive these gradual changes—in fact, frequently their wives and partners see the problems most clearly, especially when it comes to mood and behavior. “I sometimes ask a man if he feels crankier or more short-tempered than he used to,” Morgentaler relates. “Often the guy will say ‘No, not really,’ but his wife will exclaim ‘Oh my gosh yes, that’s exactly what’s going on! I thought it was just me!’”

That seemed paradoxical—doesn’t testosterone cause men to have a short fuse, to be ready for a fight, and to be reactive? “That’s just one of the many misconceptions about testosterone,” said Morgentaler. “It probably comes from widespread public knowledge about athletes who take a variety of steroid hormones at unnaturally high levels.8 In fact we find that men who’ve become nastier as their T levels dropped actually stabilize their moods with replacement therapy.” Researchers at Germany’s Institute of Reproductive Medicine recently provided some independent support for this observation, noting that “testosterone substitution can increase positive mood and decrease negative mood.”9

Obstacles to Acceptance of T Replacement Therapy

But there are less obvious reasons to be concerned about declining testosterone levels—reasons that relate to total body health, not just behavior and performance, sexual or otherwise. According to Canadian expert Dr. Jerald Bain, “Testosterone is more than a ‘male sex hormone.’ It is an important contributor to the robust metabolic functioning of multiple bodily systems.”8 Dr. Morgentaler concurs, vehemently. “Testosterone stimulates and maintains muscle and bone growth, for example—many men don’t realize that low T puts them at increased risk for osteoporosis with advancing age. It also stimulates red blood cell production, helping to prevent anemia.” Testosterone levels are reduced in type 2 diabetes and the metabolic syndrome, and although cause and effect remain unclear, therapy with testosterone in these conditions can reduce LDL cholesterol, blood sugar, glycated hemoglobin, and insulin resistance.8,10,11 Finally, Morgentaler notes, “Men with low T die earlier than those with normal T.”7,12 That alone is ample reason to take notice.

Summarizing the “Why should we care” question, Dr. Morgentaler said, “If I told you of a known medication that can improve mood and performance, while reducing the risks for a host of chronic, apparently age-related conditions, and has the real potential for increasing longevity, you would jump at it. Well, there’s solid evidence for all of that with responsible TRT. Men who feel old, have decreased ‘get up and go,’ and diminished sex drive may not simply be ‘getting old;’ they may be suffering from a treatable hormone deficiency.” The good news is that Morgentaler believes there’s a growing awareness of this issue, both among lay people and physicians: “I predict that within 5-10 years primary care physicians will be checking T levels routinely, and that men will know their T levels just like they know their cholesterol and PSA levels today.”

Obstacles to Acceptance of T Replacement Therapy

Why will it take even that long for such a successful approach to become mainstream? “There are three fundamental obstacles to widespread acceptance of TRT,” Morgentaler observed. “The first is that the benefits, though clear, have not been as well-documented in the literature as they should be, and therefore physicians simply don’t get a chance to learn as much as they could. Paradoxically, testosterone was ‘grandfathered’ into approval by the FDA years ago, so its benefits weren’t as rigorously demonstrated as would be required today. That means that, until recently, physicians didn’t have a large body of evidence to turn to. Fortunately, that’s changing with an increased number of studies on the subject.” In fact, by 2004 Dr. Morgentaler and a colleague found sufficient data to write a review article for the New England Journal of Medicine in which they provided the kind of summary that modern physicians need in order to best understand both the benefits and the possible risks of TRT.4

“Another obstacle to acceptance is that the diagnosis of testosterone insufficiency has been and is confusing to people both within and outside of medicine,” Morgentaler continued. “One of the main benefits I hope that my book will provide is to help individuals and their physicians to decide if low T is actually present or not. Some of this confusion has had to do with lack of awareness, some with lack of understanding of the various ways of measuring testosterone, and some with variations in the standards that laboratories use in reporting it.”

“The last, and possibly greatest, hurdle to overcome is the persistent idea that TRT causes prostate cancer,” Dr. Morgentaler went on. “As I point out in my book, this concept turns out to be based on a very few, very sketchy, and very old reports, most of which have also been very inaccurately cited—but cited so frequently that they’ve taken on the aura of truth. In fact, while prostate cancers do usually need testosterone to grow, there’s interesting laboratory evidence that prostate cancer cells behave less aggressively in the presence of testosterone than they do without it, suggesting that normal levels of testosterone may even turn out to be beneficial for men with prostate cancer.13

“Fortunately,” Dr. Morgentaler concluded, “all of these barriers are now relaxing, as it becomes clear how many body systems rely on healthy, normal T levels, and how normal T levels contribute to prevention of cardiovascular disease, diabetes, and the metabolic syndrome.”10,14