"There are serious potential side effects, and there's this wide-held misperception that these compounds are safe," said Dr. Shalender Bhasin, co-author of the new study and director of the research program in men's health at Brigham and Women's Hospital.
About a dozen pharmaceutical companies have been developing SARMs since the mid-1990s, Bhasin explained. Designed to help people with diseases such as muscle wasting, they are intended to have beneficial effects similar to those of testosterone, which can increase muscle and energy, without negative side effects such as blood clots and enlarged prostate.
Some SARMs have undergone limited human testing, but others have not, so their overall safety and efficacy remains unknown, Bhasin said. Still, early research has shown that in large doses, they can suppress natural production of testosterone and induce infertility. They also might have psychiatric side effects, including mania and suicidality.
, including liver toxicity, have occurred in people taking SARMs, which also have the potential to increase the risk of heart attack and stroke, according to the FDA.
"Young men, almost exclusively young men, they're using these compounds to improve their appearance," Bhasin said.
He collaborated with researchers from the US Anti-Doping Agency and the Uniformed Services University of the Health Sciences to conduct the new study, which began with a simple Google search.
Testing the products
Common names for SARMs include ostarine, andarine, RA140, ibutamoren, GW501516 and SR9009. Searching for these terms online, Bhasin and his colleagues found more than 210 products, most of which were either out of stock or unavailable. However, the research team was able to purchase 44 drugs that they evaluated using the World Anti-Doping Agency's
approved chemical analysis procedures.
About half -- 23 products -- contained SARMs. An additional 17 products (39%) contained one or another unapproved drug, such as growth hormones or steroids, that have been banned by the anti-doping agency.
Meanwhile, only 18 of the 44 had an active compound that matched what was listed on the label, and a quarter of the products had detectable amounts of the listed compound at a different amount than stated on the label. In eight products, label ingredients remained undetectable.
When he first heard the "unsubstantiated reports of SARMs and other appearance- and performance-enhancing drugs" being sold online, he was "incredulous," Bhasin said.
Regulation and enforcement
"The whole basis of commerce is that you buy something either on the internet or in a store, and it has a label that shows what is in the container, and it tells you what the product is and how much is being sold," Bhasin said. "Just imagine, you go to the grocery store and you want to buy baby food for your children" -- but the contents are not what the label says, or "worse, it contains something else whose safety is unknown."
Drs. Richard J. Auchus and Kirk J. Brower of the University of Michigan wrote in an editorial that accompanies the new study, "How can these pharmaceutical agents be widely available to the public without FDA approval, prescription, or manufacturing oversight?"
"Rapid developments in information technology, consumerism, medicine, and public policy" all play a role in the availability of these substances, explained Auchus and Brower, who were not involved in the new study.
Noting that the 1994 Dietary Supplement Health and Education Act exempted products classified as "dietary supplements" from rigorous studies prior to marketing, the "result was a flood of unregulated" products. Androgens (male hormones) were "aggressively marketed as supplements, even though these compounds are drugs and not food," Auchus and Brower wrote. Many "so-called dietary supplements still contain hormones, drugs, and known toxins often not listed on the label," they wrote.
Who is responsible for clamping down on these products?
Although the FDA is duty-bound to take action against adulterated or misbranded dietary supplements after they reach market, the agency "does not have the resources to address all of these cases," Auchus and Brower noted.
The FDA recently issued warning letters
to three companies for distributing products that contain SARMs. Marketed and labeled as dietary supplements, the products are actually unapproved drugs no evaluated for safety, according to the FDA.
Lindsay Meyer, a spokeswoman for the FDA, said these letters are warning shots for every company in the industry, not just the companies that receive them.
It's been difficult to police this activity because "most of these are being sold in dietary supplements so they don't require any kind of premarket review," said Meyer. "The internet is far more vast than the FDA is. As soon as we go after one of these websites or sellers or something, another one just crops back up in their place."
The US Drug Enforcement Administration shares responsibility for enforcement of laws regarding the sale of SARMs. "However, the DEA is overwhelmed with the opioid epidemic, and industry-sponsored legislation last year seriously impaired efforts of the DEA to thwart complicit narcotic distributors," the editorial authors wrote.
The DEA did not respond to a request for comment.
"There's no way that the authorities can intercept them, because there's such a huge flood across our borders from so many sources, it would just be prohibitively expensive to intercept them," said Dr. Harrison Pope, a professor of psychiatry at Harvard Medical School-affiliated McLean Hospital who was not involved in the new study.
He said "thousands upon thousands" of websites offer these drugs, which pour into the United States from numerous sources around the world.
"It is an important study that I hope will further awaken the population especially people who are would be purchasers to the hazards and the unpredictability of this mushrooming internet scene," said Pope, author of another study
that looked at performance-enhancing drugs sold on the Web. "With high probability you either will not be getting what you thought you were getting, or you will be getting other drugs of unknown toxicity that were not advertised in what you were getting.
"It's a problem that is not gonna go away, and if anything, it's going to increase as the years go by."
Letter of the law
When asked about the misrepresentative labels found in the new study, Sam Steger, a spokeswoman for MedFit Rx Inc., a company that sells SARMs, said, "it is imperative that our labels reflect the contents of our products accurately. We are of course familiar with the 'buzz' in the industry, but cannot speak to the internal workings of other companies."
Steger said her company's products fall within FDA regulation as sports supplements.
"We do not market as a dietary supplement and do not sell banned substances," she wrote in an email. "To start they are not illegal or banned substances."
She noted a 2014 law
that includes designer drugs
and "hormonal substances" under the definition of anabolic steroids, which are banned under the Controlled Substances Act. The same law states that "an herb or other botanical, a concentrate, metabolite, or extract of, or a constituent isolated directly from, an herb or other botanical" is not "a drug or hormonal substance" and would not be considered illegal.
The new study, though, found that 91% of the 44 tested products had an unapproved drug -- so just 9% were made of botanicals and not drugs.
Bhasin admits his study was not "exhaustive" and says that with "the rapidly changing nature of such internet sites, the results of similar searches will vary." Still, he bemoans the increasing use of SARMs.
"We don't have very good information, but investigators have estimated in the US alone there may be 2 to 4 million young men who have used performance-enhancing drugs sometime in their life," he said.
"Widespread perception amongst policy makers and the public is the problem of performance enhancing is really a problem of cheating in sports.
"The vast majority of people who use these appearance and performance-enhancing drugs are not elite athletes. In fact, they're not athletes at all," Bhasin said. Rather, they're teens and young men, often members of the armed forces, who want to improve their appeal.
"So we are seeing these dual epidemics of body image disorder in young men, which is also referred to as muscle dysmorphia, and the associated growing abuse of appearance- and performance-enhancing drugs," Bhasin said. "Easy availability of these compounds over the internet without a prescription is concerning because it will fuel these epidemics."