Table of contents 

Personal Note

Compound description and mechanism of action

Ostarine (MK-2866) Desired Effects and Uses

Ostarine (MK-2866) Side Effects

Miscellaneous 

Safety Profile Discussion 

Personal note

I have never used Ostarine (MK-2866) and I’m not affiliated with any SARM manufacturers/suppliers, and do not encourage its use. All information used is based on research, of which is cited. If information is missing a citation email x and the citation will be provided to further your own personal research.

Compound description and mechanism of action

Ostarine has a number of alternative names amongst research and bodybuilding circles. It is also referred to as Enobosarm, MK-2866, Gtx-024, and S-22. Ostarine is a non-steroidal selective androgen receptor modulator (SARM). SARMS are a class of drugs developed to activate the androgen receptors in specific tissues and transcribe anabolic effects. They were developed as an alternative treatment to AAS in treatment of muscle wasting conditions, in order to minimize potential impact on reproductive tissues commonly associated with AAS. 

There are a few mechanisms associated with their tissue-specific activities; 5 alpha reductase non activation, and androgen receptor coregulators. It should be noted that these are still debated and are all largely theoretical. Other theories such as non-genomic signaling and tissue distribution theories have mostly conflicting evidence.

5 alpha reductase non activation: 5 alpha reductase is only expressed in certain tissues, and that’s why DHT is found in high levels in the scalp and prostate but not in muscle tissues. It has been argued that since SARMS cannot be metabolized by 5 alpha reductase, they can’t be converted into a more potent molecule in the scalp and prostate, and their effects on these 5AR dense areas are limited to their effects only. 

Androgen receptor coregulators: Androgen receptors are found in the cytosol of the cell. When a hormone binds to the AR, this complex moves to the nucleus where it regulates gene expression. For example Testosterone is an agonist of the AR and leads to the upregulation of gene expression which increases the synthesis of contractile proteins (muscle growth). However there are also antagonists of the AR which down regulate gene expression. However SARMS are mixed agonist/antagonists, meaning they agonize AR receptors in bone and muscle, but are antagonists of the AR in tissues such as the prostate. The reason they are agonists in muscle and bone tissue, and antagonists in prostate tissue is because in bone and muscle tissue coactivators of AR are in excess whereas in prostate tissues corepressors are in excess. 

Ostarine has been shown to be a full and partial agonist, exerting full agonistic/anabolic effects on AR in muscles and bones, and partial agonistic effects in the prostate gland, and seminal vesicles. Its half life is shown to be between 14-24 hours.

Ostarine is also referred to as Enobosarm, MK-2866, Gtx-024, Veru-024, and S-22 during development. Ostarine is by a country mile the most well studied SARM, with the most safety data available. Ostarine was first discovered in 2004 and described in a paper from 2005.

According to its developer (GTx) there have been a total of 25 clinical studies involving more than 1,700 people using doses upward of 100mg.

OSTARINE (MK-2866) DESIRED EFFECTS AND USES

EFFECT ON MUSCLE MASS 

The absolute first evidence available about Ostarines positive effects on lean body mass come from a phase 1 clinical trial from 2005. Unfortunately the results remain unpublished but I was able to find details about study results from an investors press release.

The company claims that Ostarine showed positive changes in body composition such as lean body mass after 14 days, and comparisons were made using a DEXA scan. No drug-related serious adverse events were reported. The company also measured prostate specific antigen (PSA) and conducted cutaneous sebum analysis and found that Ostarine didn’t affect the skin or prostate either.

It’s unclear how potent Ostarine was for improving lean body mass, they just describe the effects as positive.

Next was a phase 2 clinical trial on 60 elderly men, and 60 elderly women. The paper was titled ‘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’. Subjects were administered 0.1, 0.3, 1, and 3 mg doses of Gtx-024 (Ostarine) for 12 weeks. Changes in lean body mass were seen for all dosages, however the 3mg dosage was the only group to have achieved statistical significance. Changes in LBM were measured in grams, with the mean absolute change for the 3mg being 1,246.3 g or 1.24 kg.

The percentage changes in lean body mass were also provided. 

The study also measured androgenicity in women as facial hair growth, and in men as prostate growth, both of which were observed to be minimal after Ostarine treatment.

The next study published in 2013, titled ‘Effects of enobosarm on muscle wasting and physical function in patients with cancer: a double-blind, randomised controlled phase 2 trial’, examined Ostarine’s ability to treat muscle-wasting associated with cancer. Researchers mentioned statistically significant increases in lean body mass with those treated with 1mg, or 3mg of Ostarine, after a duration of 113 days (roughly a month longer than the phase 2 mentioned above). The increase in lean body mass (LBM) was 1.5 kg for the 1 mg dose and 1.3 kg for the 3 mg dose.

Interestingly, the 1.3 kg increase in LBM with the 3 mg dose aligns with findings from the earlier phase 2 trial. However, that trial was about one month shorter, suggesting that after 12 weeks (the duration of the phase 2 trial), further gains in LBM plateaued.

In a study titled ‘Enobosarm and lean body mass in patients with non-small cell lung cancer.’, patients treated with Ostarine had a statistically significant increase in LBM. Interestingly these increases in LBM still occurred despite mean BW declining. 

Additionally, GTx conducted a phase III clinical trial involving Enobosarm treatment for muscle-wasting. The researchers concluded that Ostarine did not meet pre-specified criteria, however according to information from BusinessWire, CEO of GTx still announced that it had positive effects on muscle mass.

Looking towards the future, it has been announced Ostarine is now being developed for prevention of muscle wasting caused by GLP-1 receptor agonists (i.e. semaglutide), as well as an ongoing phase III trial for breast cancer treatment.

Something important to note is that the ongoing phase III trials on breast cancer treatment, are measuring increase in lean body mass and muscle strength as a secondary measurement, and are using doses of 9mg, 3 times higher than the previous phase III trials on treatment of muscle-wasting. The previous Phase III may have failed because Ostarine dosage was too low.

Anecdotes online are aligned with the study results that Ostarine has some positive effects on muscle mass but they are mild, especially when compared to other anabolic agents. 

One relevant insight that I noticed during my research deep dive is that out of all the data about LBM changes from SARMS, Ostarine had the greatest standard deviation. This means that the range of changes in LBM was highly variable. What this indicates is that an individual’s genetic response to Ostarine plays a much bigger role in building muscle, than other SARMS. In layman’s terms the mean increase in LBM from people taking LGD-4033 or another SARM, will be greater than the mean increase in LBM from people taking Ostarine, however some people will respond particularly well to Ostarine. 

Because Ostarine is viewed as a mild anabolic agent, it is typically taken during maintenance phases, whereas LGD-4033 is taken during blasts. 

EFFECT ON BONE HEALTH

As you’d expect from a SARM, Ostarine is able to improve bone density, by fulfilling the positive actions androgens have on maintaining bone health.

In a study titled ‘Treatment of osteoporosis using a selective androgen receptor modulator ostarine in an orchiectomized rat model’ 

Ostarine therapy was most effective in increasing density on femur. Researchers acknowledge that despite improvements in bone structure, the biomechanical properties of the bone were only slightly changed.

These findings were also consistent with a previous study titled ‘Evaluation of ostarine as a selective androgen receptor modulator in a rat model of postmenopausal osteoporosis’. Researchers in this paper also mentioned that structural improvements were significant however biomechanical properties were not significantly changed.

 

In both papers researchers speculated that they believed longer treatments would have improved biomechanical properties.

Another paper titled ‘Effect of Selective Androgen Receptor Modulator Enobosarm on Bone Healing in a Rat Model for Aged Male Osteoporosis’, found Ostarine had a positive effect on bone health, but in the discussion section researchers acknowledge that Testosterone treatment outperformed it in measured metrics.

 

It would be prudent not to mention that all these studies are in animal models and there isn’t currently any human data I can find, but it is worth mentioning nonetheless. More studies are needed to make any solid conclusions within this line of enquiry. 

EFFECT ON TENDONS

Ostarine has been reported anecdotally to be extremely beneficial for tendon healing and recovery, relative to other SARMS. As far as I can tell this has not been reported in clinical research. 

EFFECT ON STRENGTH 

In the study ‘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’, researchers examined Ostarines effect on strength output.

3mg was the only group to achieve statistical significant increases in this measure of strength in the elderly subjects, however all power measures were greater than placebo (0.1, 0.3 and 1mg).

Anecdotally Ostarine has been reported to have a mild increase in strength, however it is generally considered to be a less potent strength builder compared to LGD-4033 and RAD-140.

LACK OF ANDROGENICITY

To be clear, Ostarine leads to a dose-dependent boost in androgenic activity in the body.  Although it’s highly selective for muscle and bone compared to other androgen-sensitive tissues, all SARMs, including Ostarine, will inevitably lead to a general rise in androgen activity. 

The potential for androgenic side effects are still present, and frankly at the doses taken recreationally are significant, but it is undeniable that they are less potent to AAS.

Interestingly, many studies report this lack of androgenicity.

Within ‘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’. Researchers reported that there was no evidence of androgenic side effects within the trial.

The study measured facial hair growth in women as one measure of androgenicity and found Ostarines effects to be negligible. 

In the first human trial on Ostarine according to the investors press release, there was an apparent lack of androgenicity. The company measured prostate specific antigen (PSA) and conducted cutaneous sebum analysis and found that Ostarine didn’t affect the skin or prostate either. However it is unclear what dose was administered. 

OSTARINE (MK-2866) SIDE EFFECTS

EFFECT ON TESTOSTERONE

Within the study titled ‘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’ Ostarines suppression of Testosterone was examined. 

3mg of Ostarine on average suppressed total testosterone by ~230 ng/dl (converted from pmol/L). For comparison sake 1mg of LGD-4033 suppressed total testosterone by ~300 ng/dl. Clearly, Ostarine is a less suppressive SARM than LGD-4033. It is viewed online as one of the least suppressive SARMS.

However it had a very suppressive effect on SHBG. According to the researchers, reductions in SHBG in men/women (−61% and −80%, at 3mg respectively) were far greater than those observed in men treated with a 600 mg testosterone enanthate (−31%) injected intramuscularly.  

It should be noted that levels of DHT, total and free Testosterone, and Estradiol didn’t differ from placebo amongst women treated with Ostarine. However, online anecdotes by women suggest otherwise.

EFFECT ON LIVER HEALTH

In the trial titled ‘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’ temporary spikes in ALT above the normal range were seen in 8 participants. Concerningly, one participant had to discontinue Ostarine when their ALT level rose 4.2 x the ULN (Upper limit of normal), however for the other 7 ALT levels returned close to baseline even though they continued Ostarine administration. 

Keep in mind this was noted at a 3 mg dosage, but recreationally Ostarine is commonly taken above 10 mg and even 20 mg.

From what i’ve seen also looking at evidence of liver toxicity regarding RAD-140 and LGD-4033, it seems Ostarine may have the most potent liver toxic effect out of all the SARMS.

There are also many case reports of liver damage induced by Ostarine administration, however there is a clear flaw in these case reports. 

Firstly case reports rank at the bottom of the scientific hierarchy of evidence. Secondly, case reports are retrospective. The patients say they took Ostarine, but there’s no regulation ensuring the quality of SARMs products. So, while the bottle might be labeled Ostarine, there’s no way to confirm that’s actually what they took. There is no quality control on research compounds, and it is probable that many of them contain contaminants and other compounds aside from the SARM advertised, and many don’t even contain the SARM. There are many reviews and reports that test the quality of SARM suppliers and they are damning to say the least.

EFFECT ON LIPID LEVELS

Also within ‘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’ is an assessment on patients lipid profiles. Researchers noticed a dose-dependent reduction in HDL levels amongst Ostarine treated groups, which achieved statistical significance. However there was no significant effect on LDL levels amongst Ostarine treated groups.

These results are comparable to that of LGD-4033. LGD-4033 also reduced HDL, and did not affect LDL levels, however achieved this at a lower dose (0.3mg).

EFFECT ON ESTROGEN + GYNECOMASTIA

There are existing case reports that link Ostarine to the development of Gynecomastia, however as mentioned before these are not high quality sources. With that being said, by examining the mechanistic understanding of SARMs, it is clear Ostarine could induce this side effect in some.

The growth of glandular tissue in men is due to an imbalance in male and female sex hormones in breast tissue. Ostarine does not aromatise into Estrogen, or 5 alpha reduce.

As a result of Ostarine administration, less androgens can bind to AR and thus more is available to be aromatised into estrogen, and the suppression of testosterone can cause there to a hormonal imbalance (androgens relative to endogenous) which leads to gynecomastia formation. 

This is an issue commonly reported in anecdotes.

Ostarine also has a weak affinity for progesterone receptors, and actually acts as an antagonist, demonstrating weak anti progestogenic effects, so it is likely that gynecomastia formation is estrogen mediated. 

Depending on an individual’s hormonal profile earlier, and other factors, an individual might experience low estrogen or high estrogen. Each state carries its own side effects which can be viewed in a separate article.

MISCELLANEOUS

Why did the earlier Phase III trial on Ostarine for muscle wasting potentially fail?

Researchers involved in studies of Ostarine have speculated the doses administered were too low to offset the muscle wasting seen from cancer, and higher doses are being investigated in ongoing trials.

How does the genetic response to Ostarine differ from that of other SARMs?
As mentioned before, compared to other SARMs Ostarine seems to have the most varied responses, indicating genetic differences play a large role in an individuals experience with this compound. If I had to speculate what these specific genes would be, I’d guess particular polymorphisms in the androgen receptors (CAG repeats) and also polymorphisms of CYP3A4 the enzyme that metabolizes Ostarine.

At what doses do the potential androgenic side effects of Ostarine become significant?

Speculatively, above 5 mg.

How does Ostarine’s suppression of SHBG compare to that of other SARMs and anabolic agents?

Ostarine suppresses SHBG greater than other SARMS, and milligram for milligram is much more suppressive than Testosterone. 

What are the long-term effects of Ostarine on liver health, especially at doses exceeding 10-25 mg?

Unknown, but the growing number of case reports are concerning.

Is Ostarine legal to buy and use?

This depends on which country you are in, but for most countries it is technically legal when bought and sold for research purposes, and as a result many SARM suppliers (despite often hyping up its abilities) market them as a product only intended for ‘research purposes’. It is essentially a legal exploit.

When is Ostarine typically used recreationally amongst bodybuilding circles?

Maintenance phases. However it has demonstrated muscle-sparing qualities, allowing patients to maintain and even increase LBM whilst declining in BW.