Chances are, if you’re a man in the United States, you’ve seen some variation of this ad: “Are you tired? Stressed? Low libido? Ask your doctor if testosterone is right for you.”
Prescribed to men as a salve for symptoms that include low sex drive, fatigue, moodiness, depression and other ailments commonly related to aging, testosterone replacement therapy, or TRT, has become one of the most widely prescribed medications in the United States today.
Yet there is much debate over the benefits, risks and appropriate use of TRT.
While testosterone replacement therapy — such as AndroGel, made by pharmaceutical company AbbVie — has been found to lead to modest improvements in libido and sexual function in men over age 65, there is limited evidence that it works for many of the other symptoms for which it is advertised. In fact, recent trials of testosterone treatment in older men, supported by the National Institutes of Health, have shown inconsistent results.
What’s more, TRT, which can either be injected or applied topically, may cause serious side effects; in 2015 the FDA made drug companies add a warning to the drug labels for the potential increased risk of heart attack and stroke in men over age 65. For those under age 45, the potential side effects include increased risk of infertility. Clinical trials and data analyses continue to study these concerns.
Eli Lilly, AbbVie and other drug makers are currently facing thousands of lawsuits from men claiming to have suffered side effects. Last year the FDA recalled Axiron, made by Eli Lilly, previously AndroGel’s biggest competitor, and recently rejected multiple proposals for a testosterone pill. This was largely due to safety concerns.
A booming $3.8 billion market
Despite this, the TRT market — expected to reach $3.8 billion globally by 2022, up from $2 billion in 2012 — is booming. According to Global Industry Analysts, the uptick is being fueled by the growing prevalence of hypogonadism due to the increase in the aging male population. Hypogonadism is the medical term for the condition in which the testicles don’t make enough testosterone. The condition, roughly defined as having a level under 300 ng/dl, affects about 30 percent of men over age 65.
Other factors include the rising awareness of the disease, improved diagnosis rates, availability of therapies, preference for easy-to-use products and expected approval of new-generation drugs in the pipeline, said Global Industry Analysts.
Another major driver is the overprescription of TRT to young men, wooed by the promise of heightened energy, muscle mass and sex drive. Between 2003 and 2013, TRT use quadrupled in men between 18 and 45 years old, who most frequently were prescribed the medication by their doctors, outpacing prescription in older men for whom the drug is intended, according to a 2017 study in the Journal of Urology.
The increase is “obviously driven by the bottom line and an enormous opportunity to make money,” said Lawrence Ross, a urologist and professor at the University of Illinois at Chicago, who co-authored the study using data from the CDC. “There’s no question that the intense direct-to-consumer marketing sparks interest in young men who then ask their doctors about the drug,” Ross said.
The industry has a “tremendous amount of conflicts of interests,” said Thomas Perls, a professor of Medicine at Boston University, who describes TRT as “disease mongering,” or “redefining a disease so that it greatly enlarges the potential population that would be interested in the drug, with the addition of mass marketing,” he said.
What you need to know
Testosterone is the primary male sex hormone, mainly responsible for initiating the growth of the testicles, penis and body hair. It also causes the voice to deepen and muscle mass to increase.
Depending on age and individual makeup, typical testosterone levels in adult men range widely, from 280–1,100 ng/dl, according to researchers at the University of Rochester. Most adult men average about 679 ng/dl, although some researchers suggest that 400–600 is optimal in healthy individuals. Testosterone decreases naturally with age, but slowly, at a rate of about 1 percent a year after age 30. Low testosterone can also be caused by tumors in the pituitary gland or testes, especially in younger men, as well as diseases such as type 2 diabetes. It also has been strongly linked to obesity.
So what are the signs of low testosterone? They include low sex drive, fatigue, loss of muscle mass, decreased bone mass, increased body fat and mood changes, including irritability or lack of focus.
Multiple studies have found that testosterone effectively boosts libido and sexual function for older men with hypogonadism. TRT also has been linked to modest increases in bone density, muscle tone and grip strength.
But few of the other claims about TRT, which typically costs about $400 a month and is sometimes not covered by insurance, pan out. For instance, several recent studies corroborating TRT’s positive effects on libido in older men with hypogonadism also found that TRT had no meaningful effect on fatigue, depression, memory, emotional state, enhanced cognition, mood or energy — the two most common reasons men give for seeking out the drug, other than libido — compared to control groups. In addition to the increased risk of heart disease and stroke, scientists currently are debating the role of TRT in the development of prostate cancer.
Comparatively, hypogonadism affects about 3 percent to 5 percent of men under age 45. For them, side effects may be much more dangerous, including permanent infertility, said Halis Kaan Akturk, a professor of medicine at the University of Colorado and formerly a doctor at the Mayo Clinic. Akturk said he sees at least one patient per day seeking testosterone, many of them former student athletes now in their 20s and 30s, who began taking testosterone early and are now dependent.
“If we give someone testosterone, we are making their testicles lazy,” Akturk said. “In these patients, who have been using testosterone for five to six years, their testicles get atrophied and sometimes permanently damaged. It’s a hard thing to wean people off of.”
What’s more, abnormally low testosterone in younger men can indicate a different, often serious problem, which artificially upping testosterone levels can make the both harder to detect and treat, Akturk said. Treatment for prostate cancer, for instance, a common cause of abnormally low testosterone in young men, typically involves decreasing the amount of testosterone in the bloodstream. Excess testosterone can “wake sleeping tumors,” Akturk said.
Akturk was part of a team of Mayo Clinic doctors who treated a 56–year-old man who went blind in both eyes soon after starting testosterone therapy prescribed by his doctor. Akturk and the other doctors traced the blindness — as well as the man’s original symptoms, for which he sought testosterone therapy and which still had not abated — to a tumor in his pituitary gland. The testosterone, they found, had stimulated the tumor further.
After stopping testosterone therapy and prescribing medication to decrease the amount of testosterone in the bloodstream, the man’s eyesight mercifully returned. “It needs to be worked out why this person has low testosterone, rather than just giving them testosterone,” Akturk said.
That does not appear to be happening in practice, however. Only half of the men at a medical center interested in TRT had a clinical diagnosis of hypogonadism, according to a 2017 study by researchers at Emory University School of Medicine, and about 10 percent knew about side effects.