The Beef on Selective Androgen Receptor Modulators (SARM)

The Beef on Selective Androgen Receptor Modulators (SARM)

Josh Baker, MD

Background concept wordcloud illustration of steroids synthetic hormones glowing light SARM

In 1999, Ligand Pharmaceuticals created something new. A drug that mimicked testosterone, but was more selective for skeletal muscle than previous versions of androgens. In their pursuit to treat muscle wasting in patients with cancer they developed what is known today as nonsteroidal selective androgen receptor modulators, (SARMS).

Regardless of the original intended audience, the advent of an anabolic drug with the potential for “golden” selectivity of muscle, made it immediately attractive to the athletic world.

     Today SARM use is becoming more and more common. Recent featuring in Maxim magazine this year points towards its rise. SARM’s are like testosterone but different. First, SARM’s can be taken orally. Traditional testosterone supplementation does not have the chemical makeup to withstand the digestive system. Second, they have selective preference for the androgen receptor in skeletal muscle and bone over prostate tissue. This allows for the preferential expression of anabolic activity in muscle and bone. Third, they avoid being converted to estrogen and dihydrotestosterone. These items together should in theory lower the risk of side effects such as prostate enlargement, prostate cancer, virilization in women and cardiovascular disease. Whether this theory holds water is currently up for debate.

Here is where we should highlight something.   There are many different versions of this drug and all have weird names like LGD-4033 and MK-677 for a reason. That’s what the researchers in the lab call them, because they are STILL researching them. And this point is important to understand because this is not a supplement like we are used to hearing about them. It is not available at GNC. It is a research drug that can be bought online through thinly veiled “research purposes only” taglines and falls into a weird loophole where it is not considered illegal. There are plenty of online sites extolling the virtues of SARM’s and you’re free to review all of them. But that unlimited well of positive product feedback has a name: selection bias. Only those who love the results, real or not, are going to take the time to report online. The rest are just going to move on. And that’s not science or reliable. While no version of SARM’s, has completed clinical trials yet, some evidence is out. So let’s do what we do here, and review the hell out of it.

human body SARM

In an exponentially increasing number of synthetic wannabe steroids, do any of them even work? This is a hard question to answer with literature, because again no SARM has even finished phase III trials, but some data has been published on those closest to the finish line. In one of the most recent studies done with LGD-4033 it was seen that after 21 days lean body mass increased by 2.2 lbs (1.21 kg) at a 1mg per day dose. This was the highest dose studied of LGD-4033 and there are two things to point to here. One, there is no comment on the workout habits of the participants and many may not have been working out at all. It is likely that there is potential for much greater gains in those who engage in strength training while taking SARM’s. Two, the dose of 1mg/day did suppress free testosterone, total testosterone, and sex hormone-binding globulin. This is similar to what happens when taking injectable testosterone and implies that indeed anabolic activity is occurring.

So at first brush, it seems to work. Where do I sign?

     However, and this is a huge monumental however, there are still side effects. In the LGD’s trial there was a significant drop in the same group’s HDL level by an average of 19 points. HDL as you will remember is the good cholesterol that protects you from atherosclerotic heart disease. This level did return to normal after discontinuing the study but most people do not see HDL drops as a good thing, and this is one of the same major problems seen with traditional injectable androgens.

Let’s take a look at another leading contender. GTx-024 (enobosarm) was studied in a double-blind, placebo-controlled phase II trial and demonstrated improved lean body mass. All of the subjects were over 60 years of age and included 120 healthy men and women. Again there was a statistical lean body mass gain demonstrated in this 12 week trial with an average gain of ~2.8lbs (1.3 kg) at 3mg/day over 86 days. The study group was also instructed at the start to not change their diet or exercise regimen. Again, the SARM appears to be responsible for the gain in lean body mass. However, once again, at doses needed to gain mass, HDL was suppressed. Other versions of SARM’s have demonstrated far worse side effects. Vision changes are reported frequently with S-4 (Andarine), and GW501516 (Cardarine) has been reported to cause cancer in test animals. And these last two SARM’s are still aggressively marketed and hard to distinguish from other available SARM’s for the consumer.

So looking at the above as examples of the class, what can be concluded.   They are more selective, but not exclusive, to the androgen receptor present in muscle and bone over prostate. This should in principle make them safer. They are likely to increase lean body mass in the athlete and non-athlete alike. However, in clinical trials, the most studied SARM’s to date, still drop your HDL, and it is this HDL decrement that is associated with atherosclerotic disease. This isn’t that far different from traditional injectable testosterone. SARM’s have also caught the attention of the U.S. Anti-Doping Agency who has outlawed their use in competitive athletes and tests for them.   Finally, the SARM’s available online are often the ones with the more concerning and severe side effects.

As the pharmaceutical companies continue to fine tune SARM’s with their chemical Darwinism, athletes are left assessing their personal risk limits. The literature has begun to give credence to the online claims for SARM’s ability to create lean muscle gains. But a version with zero side effects does not exist today. Regardless of your opinion as to whether the risk is worth it, SARM’s seem to be rising as the new vogue androgen.

-Josh Baker MD

Josh Baker Is a contributing author to HPU.  He is an active duty emergency medicine physician who trained at the San Antonio Military Medical Center.  Currently Josh is doing a victory lap by training as a sports medicine fellow in Washington, D.C.  He swears on a stack of Bibles this will be the last year of formal education.



  • Basaria S, Collins L, Dillon E, et al. The safety, pharmacokinetics, and effects of LGD-4033, a novel nonsteroidal oral, selective androgen receptor modulator, in healthy young men. J Gerontology. 2013 January; 68(1): 87-95
  • Dalton J, Barnette K, Bohl C, et al. The selective androgen receptor modulator GTx-024 (enobosarm) improves lean body mass and physical function in healthy elderly men and postmenopausal women: results of a double-blind, placebo-controlled phase II trial. J Cachexia Sarcopenia Muscle. 2011; 2:153-161.
  • Bhasin, S, Jasuja R. Selective Adrogen Receptor Modulators (SARMs) as Function Promoting Therapies. Curr Opin Clin Nutri Metab Care. 2009 May; 12(3): 232-240.
  • Basaria S, Coviello A, Travison T, et al. Adverse Events Associated with Testosterone Administration. New England Journal of Medicine. 2010 July. Vol. 363 No. 2
  • Bhasin S, Storer T, Berman N, et al. The effects of supraphysiologic doses of testosterone on muscle size and strength in normal men. New England Journal of Medicine. 1996 July; Volume 335
  • Rossen, Jake. A new class of unapproved supplements has mass appeal. Maxim Magazine. 2015 April




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76 responses to “The Beef on Selective Androgen Receptor Modulators (SARM)

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