What Are SARMs & Other SARM Questions Answered
Dr. Adam Watson from Umbrella Labs is here to answer some of the most common questions regarding SARMS. Depending on who you ask, SARMS are either:
- function promoting anabolic therapies
- the next blockbuster cancer drugs
- bone-strengthening agents that promise to reduce the burden of frailty & physical disability in our aging population
- a totally new approach to managing lung disease and dementia.
The truth is, SARMS have the potential to transform human health in extraordinary ways, which is what makes them so exciting.
What are SARMs?
Selective Androgen Receptor Modulators are exquisitely designed small molecule compounds that can either activate or repress the Androgen Receptor in our cells. The Androgen Receptor is a protein that changes how genes are turned on or off in many of the tissues in our bodies, and it’s responsible for coordinating a huge range of cellular activities, like tissue growth, sexual development, metabolism, blood cell formation, and even neurological functions that affect mood.
The most common androgen in the body is testosterone, which activates the Androgen Receptor. The main difference between testosterone and SARMS is that SARMS are engineered to selectively function in some tissues, like muscle and bone, while sparing other tissues, such as the prostate.
The rationale for developing SARMS was to maximize the benefits of testosterone while minimizing the drawbacks. Currently, testosterone and related steroids are prescribed to trigger anabolic growth when medically advisable, and they are certainly effective, but in many cases it’s like using a sledgehammer to drive in a nail. It’s just not the right tool for the job, and you might end up breaking something in the process.
One of the most common misconceptions about SARMS is that they are new compounds. As a matter of fact, SARMS have been in development for almost 80 years, but the pace of research has really picked up in the last decade as most of the major international pharmaceutical companies have joined the race to bring SARMS to market.
In many cases, SARMS are being developed as an alternative to using steroid hormones clinically, which brings us to our second question.
Are SARMS considered steroids?
Virtually all of the SARMS currently in development are non-steroidal, including all of the examples mentioned. Many people tend to think of steroids based on a physiological effect, but steroid classification is actually based on the presence of a distinct molecular ring structure. Some steroids are anabolic, like testosterone, whereas other steroids like hydrocortisone are not anabolic whatsoever.
Regardless, most SARMs do not contain the steroidal ring structure, so they are not classified as steroids, and the lack of that distinct structure has important implications on how the human body can use them. For instance, testosterone can be converted into estradiol, which is a form of estrogen, yet nonsteroidal SARMs cannot be similarly converted.
This lack of conversion to estrogen is actually a crucial part of the value proposition for employing SARMs to address particular health conditions, like in the case of breast cancer, because estrogen drives many forms of that disease. In fact, one of the ongoing clinical trials of SARMS is investigating whether RAD-140 can improve survival in breast cancer patients, because RAD-140 blocks the growth of breast cancer cells, and it doesn’t convert to estrogen like testosterone does, which is why testosterone may indirectly promote estrogen-dependent tumor growth in some patients.
Why do SARMs generate such excitement?
There are a few main reasons for the abundance of interest in SARM research among scientists and physicians. First, the potential therapeutic indications are quite broad, and they include prostate cancer, breast cancer, osteoporosis, sarcopenia, dementia, chronic obstructive pulmonary disease, and muscular dystrophy.
Secondly, many of the clinical trials of SARMs that have been completed have shown encouraging results with excellent tolerability and minimal adverse effects. This does not necessarily mean that SARMS are without risk, because drug safety is established over a long period of time, across multiple clinical trials, and in hundreds or thousands of patients. SARM research simply hasn’t progressed far enough yet to make broad claims of safety, but we are definitely well on our way there.
Thirdly, society will soon be burdened with an aging population. Unfortunately, lifespans do not always correlate with healthspans, As men and women age, muscle and bones deteriorate, leading to a loss of strength, coordination and mobility. This greatly increases the risk of a traumatic slip and fall that can fracture a hip and force a loved one into expensive long-term care.
It is hoped that SARMS may help prevent the loss of muscle and bone strength and extend the healthspan of our aging population, so that more people can continue to live independently throughout their golden years. Moreover, some newer SARMS, like NEP28, are being developed specifically for their potential to treat Alzheimer’s Disease, which is also a growing problem among the elderly.
Lastly, SARMS are a potential alternative to testosterone replacement therapy, or TRT, in middle-aged men. Currently, testosterone is prescribed to help manage the symptoms of andropause, which can include muscle weakness, fatigue, reduced muscle mass, osteoporosis, sexual dysfunction, depression, insomnia, and memory impairment.
The fact that SARMS are orally bioavailable and can be ingested in pill form is an attractive feature for patients, which could lead to better compliance compared to testosterone injections. In addition, despite the fact that TRT is generally well tolerated, there are common adverse effects to testosterone supplementation, including acceleration of pre-existing prostate cancer growth, blood cell abnormalities, liver dysfunction, acne, and thinning of hair.
It is hoped that future clinical trials of SARMS will evaluate these parameters in men being treated for low testosterone, and thus position SARMS as a superior alternative to conventional androgen therapy. However, more likely than not, repurposing SARMs as an alternative to TRT will eventually become an off-label use of SARMS, prescribed by a physician but not FDA-approved for that indication, because the FDA has been reluctant to approve of TRT except in men that meet very specific criteria.
So, for instance, if you’re a 40 year old guy with low normal testosterone levels, fatigue and decreased libido, but you have no other symptoms, the FDA probably won’t ever explicitly condone SARM therapy for you, but your doctor could still legally prescribe you a SARM, as long as it’s already approved for some other indication. And that leads us to our final question of the day.
Are SARMs legal?
In 2019, Congress debated the SARMS Control Act, which had actually been introduced in Congress the year before, and the bill seeks to regulate SARMs as controlled drugs. However, Congress declined to move forward with the legislation for the second year in a row, and as a result, there are still no laws prohibiting the possession of SARMS in the United States.
In contrast, anabolic agents such as testosterone and human growth hormone are both Schedule III controlled substances, which means that possession of them is restricted, unlike SARMs. Nevertheless, some SARMs are patented, which prevents their sale through a different legal framework, because they are protected as intellectual property. Of course, the legality of SARMs will almost certainly change with time, but for now, Congress has decided to kick the can down the road, instead of addressing the issue. Regardless, SARMs cannot be sold as dietary supplements, and currently they can only be used for research.
Eventually, a handful of SARMS will likely become FDA approved, for a variety of medical indications, but only after successful Phase III clinical trials are completed, which is probably a few years away.
The closest that any SARM has come to approval was Enobosarm, which completed a couple of Phase III trials that brought a mix of good news and bad news. The good news was that is increased lean body mass compared to placebo. The bad news was that despite these positive results, the trial failed to meet its primary endpoints, which were to prevent the loss of body weight and physical function in cancer patients.
Unfortunately, when a clinical trial fails to meet its primary endpoints, it’s unlikely to be granted FDA approval, even though the trial demonstrated that Enobosarm was non-toxic, well tolerated, and led to increased lean body mass relative to placebo. However, it’s not the end of the line for Enobosarm, especially since it still has so much promise, just like the many other SARMS still in development, not to mention the ones that are still on the drawing board.
For more in depth coverage of the science and future prospects of SARM research and development, check out all of our educational materials on individual SARMs and related research compounds.
As always, it is essential to note that all clinical research must be done with oversight from the relevant Institutional Review Board, and all preclinical research must be done with oversight from your Institutional Animal Care and Use Committee, following the guidelines of the Animal Welfare Act.