The ads, which are directed at men over forty, are hard to resist:
Reduced Sex Drive?
Decreased Energy?
Unwanted Body Changes?
Mood Changes?
Sexual Dysfunction?
Stop Living in the Shadow. If you feel you are experiencing any of the symptoms of Low T, talk to your doctor to see if you should be tested.
Intrigued? Take the “Low-T Test”:
Do you have a decrease in libido?
Do you have a lack of energy?
Are you sad or feeling grumpy?
Are you falling asleep after dinner?
Have you noticed a recent deterioration in your ability to play sports?
Are you feeling like a shadow of your former self?
If so, you might have a treatable condition called Low T.
“Low T” stands for low testosterone, the male sex hormone. Testosterone has a variety of functions. It promotes the growth of the testicles and prostate, regulates sex drive (libido), strengthens muscles and bones, and determines fat distribution, the development of body hair, and the production of sperm.
Like many hormones in the body, testosterone levels in the bloodstream are highly regulated. When levels fall, the hypothalamus, which is located at the base of the brain, releases a hormone that stimulates the pituitary gland to release two other hormones that stimulate the testicles to produce more testosterone.
Any disease that affects this hypothalamus-pituitary-testicle axis could result in a critical decrease in testosterone, causing what doctors call “hypogonadism.” Causes of hypogonadism include genetic disorders; undescended testicles; testicular injury; infections such as tuberculosis, AIDS, and mumps; tumors of the pituitary gland and hypothalamus; radiation and chemotherapy; drugs such as opiates and antidepressants; and disorders such as alcoholism, obesity, and type 2 diabetes.
Symptoms of hypogonadism aren’t subtle. Infertility, muscle wasting, loss of sex drive, loss of body hair, obesity in the abdominal area, erectile dysfunction, decreased penile sensation, reduced ejaculate, reduced energy and stamina, depressed mood, fatigue, hot flashes, sleep disturbance, increased irritability, difficulty concentrating, poor cognition, anemia, difficulty attaining orgasm, and reduced bone density are all caused by a critical lack of testosterone.1
Typically, doctors treat male hypogonadism with testosterone tablets, implantable pellets, intramuscular or subcutaneous injections, or transdermal patches, solutions, or gels. Transdermal gels are the most popular.
Low T, however, is not hypogonadism. It’s something else. Beginning at around age thirty, levels of testosterone in men begin to decline, and they continue to decline about 1 percent every year. As a consequence, older men have lower levels of testosterone than younger men. The result is a decrease in sex drive and sexual performance and changes in muscle mass, muscle strength, and bone density. This is a normal physiological process. It’s called aging. And it’s not a disease. Nonetheless, testosterone makers have made it one, creating an enormous market for their product. Said another way, it’s the rare older man who answers “no” to all the questions on the “Low-T Test.”
The Low-T craze started in 2002. Prior to that, the gradual lowering of testosterone in older men was called andropause, which was accurate. The prefix andro- is derived from the Greek word meaning “man”; the suffix -pause from the Latin word meaning “cessation.” Andropause is the male equivalent of menopause, which also involves a decrease in a sex hormone (estrogen). By choosing the term Low T, however, testosterone manufacturers had created a label that sounded no longer like a natural process, but like a treatable disorder. Sales exploded. In 2002, testosterone makers were selling $324 million worth of their product a year. Ten years later, with an annual advertising budget of $107 million, sales topped $2 billion. Prescriptions for testosterone increased more than threefold. In the United Kingdom, they increased fourfold. When the term Low T was translated into other languages, testosterone sales skyrocketed in thirty-seven other countries.
By taking advantage of a loophole in how companies are allowed to promote their products, testosterone manufacturers had succeeded in making aging a disease. By avoiding the names of specific brands (and calling their sales pitches “disease awareness campaigns”), companies could now sell testosterone for the treatment of vague symptoms such as listlessness or increased body fat or declining sexual performance. Also, by encouraging men to take the “Low-T Test,” drug companies ensured themselves a ready market. When these nonbranded sales campaigns first launched, some medical specialists complained to the Food and Drug Administration. But they’d complained to the wrong regulatory agency. Only the Federal Trade Commission (FTC) has the authority to regulate this kind of advertising—and the FTC stood back.
In the early 2000s, the Low-T media blitz took the form of television ads, magazine articles written by physicians with ties to the drug industry, and websites explaining how dips in energy, changes in mood or sex drive, and worsening sports performance could all be explained by low testosterone levels. As a consequence, testosterone was sold to healthy men, many of whom never had their testosterone levels checked before receiving a prescription.
In 2013, Larry Dobrow, writing for the trade magazine Medical Marketing and Media, sang the praises of this new advertising effort, specifically singling out a company that made testosterone gel. Under the headline “All-Star Large Pharma Marketing Team of the Year,” Dobrow wrote, “It might be exaggerating to say that AbbVie—Abbott’s new breakout pharma division—overcame a host of challenges to establish AndroGel as the preeminent product in the low-testosterone category. Or maybe not. AbbVie took a taboo topic and, via a cagey media and marketing presence, rendered it less wince-inducing among its target audience. It did so at a time when a number of critics voiced their concerns that the marketing and use of testosterone-boosting products had gotten ahead of the science.” Nonetheless, the magazine had named AbbVie executives its “Marketing Team of the Year.” Apparently, getting ahead of the science was a good thing.2
Lisa Schwartz and Steve Woloshin, codirectors of Dartmouth College’s Center for Medicine and the Media, saw the dangers of this new approach to marketing drugs. “We should recognize it for what it is,” they wrote, “a mass uncontrolled experiment that invites men to expose themselves to the harms of a treatment unlikely to fix problems that may be wholly unrelated to testosterone levels.” The “harms,” as it turned out, were far greater than Schwartz and Woloshin could have imagined.3
No one disagreed that lower testosterone, even when associated with aging and not true hypogonadism, was linked to a variety of symptoms. Wasn’t it at least possible, manufacturers argued, that replacing testosterone in aging men could have positive effects? This question was easily studied. The results, however, weren’t what the companies had anticipated.
In 1997, researchers from St. Louis University Health Sciences Center divided thirty-two older men into two groups. One group was injected with 200 milligrams of testosterone every two weeks for a year; the other, a placebo. At the end of the trial, the men were given a series of tests of memory. No differences were detected.4
In 2000, researchers at the University of Trier, in Germany, divided thirty older men into two groups. One group was injected with 250 milligrams of testosterone; the other, a placebo. Five days later, cognitive function was determined by a series of spatial and verbal tests. Again, no differences.5
In 2006, researchers from the David Geffen School of Medicine, at UCLA, divided thirty-eight men with Alzheimer’s disease into two groups. One group was given 75 milligrams of testosterone gel weekly for twenty-four weeks; the other, a placebo. Again, the researchers found no differences in cognitive scores.6
In 2000, researchers at Hartford Hospital divided twenty-two older men into two groups. One group was injected with 200 milligrams of testosterone every two weeks for eight weeks; the other, a placebo. Six weeks after the last dose, both groups were given a series of tests to determine health-related quality of life and psychological well-being. Again, no differences.7
In 2005, researchers from the University of Adelaide, in Australia, divided seventy-six older men into two groups. One group received one 80-milligram testosterone tablet twice daily for one year; the other, a placebo. Both groups were then given a series of physical and psychological tests. Again, no differences.8
In 2001, researchers from Columbia University, in New York City, divided thirty-two men with major depressive disorders into two groups. One group was injected with 200 milligrams of testosterone every week for six weeks; the other, a placebo. The authors concluded that the purported “antidepressant effects of testosterone could not be differentiated from those of placebo.”9
In 2010, researchers from McLean Hospital in Belmont, Massachusetts, divided one hundred healthy adult men with major depressive disorders into two groups. One group received testosterone gel with the dose constantly adjusted to the level of testosterone in the blood; the other, a placebo. Participants were tested weekly for six weeks for changes in mood. The authors concluded that “Testosterone is not generally effective for depressed men.”10
In 2006, researchers from the University of Florida in Gainesville divided thirty men with Parkinson’s disease into two groups. One group was injected with 200 milligrams of testosterone every two weeks for eight weeks; the other, a placebo. Both groups were given a series of tests to determine mood, cognition, fatigue, and motor function. Again, no differences.11
In 2008, researchers from the University Medical Center in Utrecht, the Netherlands, divided 237 healthy older men into two groups. One group was injected with 80 milligrams of testosterone twice daily for six months; the other, a placebo. The authors found that lean body mass increased and fat mass decreased in those who had received the testosterone. However, researchers didn’t detect any differences between the two groups in mobility, muscle strength, cognitive function, bone mineral density, or quality of life.12
Although testosterone hadn’t been shown to work for a variety of symptoms of low testosterone, advocates were certain that at the very least it would help men with erectile dysfunction.
It didn’t work out that way.
In 1979, researchers at the Center for Maternal and Child Health in Durham, North Carolina, divided twenty-nine men into two groups. All men had a reduced or nonexistent capacity to have an erection during intercourse (erectile dysfunction). One group received daily injections of 120 milligrams of testosterone for eight weeks; the other, a placebo. The authors concluded that testosterone was “no more effective than placebo in restoring sexual potency to sexually impotent men.”13
In 1997, researchers from Mount Sinai School of Medicine, in New York City, divided twelve men with erectile dysfunction into two groups. One group received biweekly injections of 200 milligrams of testosterone for six weeks; the other, a placebo. The authors found no differences in sexual desire, masturbation, sexual experiences, sleep erections, penile rigidity, or sexual satisfaction.14
In 2012, researchers at Boston University School of Medicine divided 140 men with erectile dysfunction into two groups. One group received sildenafil (Viagra) alone. The other received sildenafil plus 10 milligrams of testosterone gel daily for fourteen weeks. The authors found that while sildenafil caused “a substantial increase in erectile function scores,” testosterone offered no additional benefit.15
In 2014, in what was probably the most aggressive study of the effect of testosterone on erectile dysfunction, researchers from Heidelberg, Australia, divided eighty-eight obese men with type 2 diabetes into two groups. Both obesity and type 2 diabetes are associated with decreased production of testosterone. One group was injected with 1,000 milligrams of testosterone every six weeks for forty weeks; the other, a placebo. Again, no difference.16
The finding that testosterone didn’t treat erectile dysfunction shouldn’t have been surprising. Erectile dysfunction is almost always associated with low blood flow to the penis, which is caused by high blood pressure, high cholesterol, and other conditions that narrow blood vessels and reduce flow. That’s why sildenafil, which increases blood flow to the penis, worked.
During the past forty years, 156 studies of testosterone have been performed across the globe. In 2018, these trials were reviewed and summarized by researchers from Tulane University School of Medicine, Georgetown University School of Medicine, and the University of South Florida. The researchers concluded that “The prescription of testosterone supplementation for low-T for cardiovascular health, sexual function, physical function, mood, or cognitive function is without support from randomized clinical trials.” Further, they found that the continued use or study of testosterone in men who did not have true hypogonadism was unethical: “We identified no population of normal men for whom the benefits of testosterone use outweigh its risks. Given the known risks of testosterone therapy and the lack of evidence for clinical benefits in normal men, we do not think further trials of testosterone are necessary.”17
The “known risks” cited by these reviewers had, unfortunately, only recently become apparent.
For decades, clinicians had known that testosterone therapy could cause acne, enlarged prostate, decreased sperm count, and sleep apnea. Indeed, some of these side effects appeared as a warning label on the product. Also, from five studies that had been performed between 1995 and 2010, testosterone was known to increase anger, aggression, and hostility.18 Because testosterone is a type of steroid, this particularly noxious side effect was called “roid rage.”
The poster boy for “roid rage” was Lyle Alzado, a defensive end for the Los Angeles Raiders in the 1980s who injected himself with testosterone for most of his fifteen-year NFL career. His steroid use began in college, when he went from 195 pounds as a freshman to 245 pounds as a sophomore to 280 pounds as a junior to 300 pounds as a senior. Alzado’s nicknames included “Rainbow” because of his mood swings and “Three Mile Lyle” because of his volcanic temper. Before Super Bowl XVIII, Alzado vowed to decapitate Washington Redskins quarterback Joe Theismann. During one game, he tore the helmet off an opposing player and threw it at him. The next season, the NFL created the “Alzado Rule,” punishing the removal of another player’s helmet with ejection and a possible fine. Alzado also once threw a chair at a newspaper reporter and said that his only regret was that he had missed. In 1991, Alzado was arrested for battery of a female police officer who, fearing for her safety, had maced him. “If me and King Kong went into an alley,” boasted Alzado, “only one of us would come out. And it wouldn’t be the monkey.”19
There was one side effect, however, that researchers hadn’t anticipated. And its discovery should end the casual use of this drug.
In 2010, researchers from Boston University School of Medicine divided two hundred men over age sixty-five into two groups. One group received 100 milligrams of testosterone gel daily for six months; the other, a placebo. Researchers wanted to determine whether testosterone increased muscle function. It did. They found that older men who received testosterone had significantly greater improvement in tests of strength. The study, however, had to be stopped prematurely when researchers noticed an abnormally high number of serious side effects in the testosterone group—specifically, increased heart rate, elevated blood pressure, chest pain, heart attacks, heart failure, heart arrhythmia, and stroke. Whereas twenty-three men in the testosterone group experienced one or more of these symptoms, only five in the placebo group experienced them—a significant difference.20
Stunned by this result, other groups looked back at their records to see if they could find what the Boston researchers had found.
In 2013, three years after the Boston researchers were forced to suspend their study, investigators from the University of Texas Southwestern Medical Center, in Dallas, examined the medical records of 1,200 veterans who had started testosterone therapy within two years of a coronary angiography, a procedure to determine whether the arteries that supply the heart are partially blocked. Researchers then compared these men with 7,500 men who also had undergone a coronary angiography but hadn’t later received testosterone. Similar to the Boston study, the researchers found that testosterone treatment increased the risk of strokes and heart attacks.21
That same year, researchers from the University of Hong Kong reviewed twenty-seven studies involving three thousand older men who had received testosterone and compared them with men of the same age who hadn’t received the drug. They found that those who had received testosterone were twice as likely to have heart artery disease, arrhythmias, heart failure, and stroke. Perhaps most discouraging, researchers found that the risk of heart problems varied with the source of funding: “In trials not funded by the pharmaceutical industry[,] the risk of a cardiovascular-related event on testosterone therapy was greater than in pharmaceutical industry funded trials.”22
One year later, in 2014, researchers from the University of California, Los Angeles, and the National Institutes of Health, in Bethesda, examined the medical records of 56,000 men who either had or hadn’t received testosterone. They found that in men over age sixty-five, the risk of a heart attack within ninety days of receipt of testosterone was greater than twice that of men who hadn’t received the drug; for those over seventy-five, the risk was almost four times greater.23
Then the FDA stepped in. On January 31, 2014, in a warning letter on its website, it tried to put an end to the myth of Low T, arguing that only men with true hypogonadism should be treated with testosterone: “Testosterone is FDA-approved as replacement therapy only for men who have low testosterone levels due to disorders of the testicles, pituitary gland or brain that cause a condition called hypogonadism. Examples of these disorders include failure of the testicles to produce testosterone because of genetic problems, or damage from chemotherapy or infection. However, FDA has become aware that testosterone is being used extensively in attempts to relieve symptoms in men who have low testosterone for no apparent reason other than aging” (emphasis mine).
The FDA then did something that it hoped would put the brakes on this ill-conceived industry, demanding a change in the labeling of testosterone: “Based on our findings, we are requiring labeling changes for all prescription testosterone products to reflect possible increased risk of heart attacks and strokes associated with testosterone use” (emphasis mine).24
On February 7, 2014, the Endocrine Society, a professional organization in the United States that represents doctors most likely to prescribe testosterone, sent a letter to its members. After the fourth study in five years found that testosterone was far more dangerous than doctors had realized, they knew that a line had been crossed. At the very least, doctors had to let their patients know what was happening. Noting that the number of men taking testosterone in the United States since 2000 had almost quadrupled, they wrote, “The Endocrine Society believes that patients should be made aware of the potential risk of [heart artery] disease in middle-aged and older men who are taking or considering taking testosterone therapy.”25
Unfortunately, the Endocrine Society’s warnings and the FDA’s labeling changes have done little to discourage men from taking testosterone for a disorder that isn’t a disorder. Millions of men still spend hundreds of dollars a month for a product that hasn’t fulfilled its promise and, worse, puts them at risk of a potentially fatal side effect.
Perhaps the most discouraging part of this story is that we have failed to learn from history and, as a result, have been condemned to repeat it.
The predominant sex hormone in women is estrogen, which is produced in the ovaries. Whereas levels of testosterone gradually decrease as men age, for women, the decline is more sudden, typically occurring around fifty years of age. The sudden decline in estrogen is called menopause, which is defined as the absence of a menstrual period for twelve consecutive months. (The prefix meno- is derived from the Greek word meaning “month.”)
Like andropause, menopause is a natural biological process. And like andropause, menopause is accompanied by a variety of symptoms, including vaginal dryness, hot flashes, chills, night sweats, sleep problems, mood changes, weight gain, slowed metabolism, thinning hair, dry skin, and loss of breast fullness.
In 1942, the FDA approved estrogen for the treatment of hot flashes associated with menopause. Beginning in the 1950s, however, health advocates started to raise concerns that estrogen might be doing more harm than good. These warnings were largely ignored. Then, in 1966, estrogen therapy took off. The launching pad was a book written by Robert A. Wilson titled Feminine Forever. Similar to the creation of the term Low T, Wilson argued that menopause wasn’t a natural process, but a preventable disease—and estrogen was the cure. Wilson wrote that with estrogen, women’s “breasts and genital organs will not shrivel. She will be much more pleasant to live with and will not become dull and unattractive.”
Feminine Forever became a national bestseller. Women flocked to their gynecologists demanding estrogen. Although it had been approved only for the treatment of hot flashes, doctors began prescribing it for all manner of symptoms associated with menopause. By 1992, estrogen was the most prescribed drug in the United States. By 1997, sales exceeded $1 billion.26
Then it all came crashing down. Between 1993 and 1998, researchers from forty U.S. medical centers recruited 17,000 postmenopausal women to participate in a randomized, controlled trial of estrogen called the Women’s Health Initiative. The researchers found that, similar to men taking testosterone, women taking estrogen had an increased risk of strokes, blood clots, and heart attacks.27 They also had an increased risk of uterine cancer.28
Andropause and menopause aren’t diseases, but they aren’t alone in being declared diseases by doctors and pharmaceutical companies. For example, moods such as sadness aren’t moods anymore; they’re affective disorders requiring medicines. Other examples abound. Chronic fatigue syndrome and chronic pain syndromes are often a somatization of life stresses or family dysfunction. Nonetheless, most of those who suffer from them are treated with polypharmacy, not counseling.
Aging is a natural process. Taking large quantities of sex hormones isn’t. Although some would argue that the phrase “aging gracefully” is an oxymoron, attempts to turn back the clock have come with a price, and it’s not insignificant.