Your Ultimate 2021 SARMs Research Review

SARMS research
Table of Contents

Selective androgen receptor modulators or SARMs have sparked a lot of conversation over the past few years. While there might be some controversy surrounding SARMs, the fact remains that there is a lot of research still happening to fully understand SARMs, including clinical trials. 

Keep reading on to see how SARMs researchers are impacting studies and trials to further developments for the future of research. This includes how SARMs are being studied for how they effect cancer patients, bone mineral density. How they are impacting clinical development program(s). 

SARMs Studies and Cancer

There have been a few studies over the past year that have looked at SARMs and their potential for their involvement with cancer. The types of cancer that SARMs could potentially treat have varied. 

Breast Cancer

One study done in 2021 looked at SARMs’ benefits in breast cancer (BC). The results of this study have preliminary findings that could be promising [1]. 

This study  looked at subjects with metastatic BC. This study is a phase 1 study, and this was the first mammalian study [1]. 

The goal of this study was to characterize the following factors when it came to an oral selective androgen receptor modulator called RAD140 [1]:

  • Safety
  • Tolerability
  • Maximum tolerated amount
  • Pharmacokinetic profile
  • Antitumor activity

The study utilized females who were postmenopausal with ER+/HER2- metastatic BC [1]. 

From this study, it was concluded that RAD140 has an acceptable safety profile. In addition, there is preliminary evidence of antitumor activity and target engagement [1]. 

Prostate Cancer (PC)

This 2021 study looked at the role of SARMs in suppressing tumor growth in subjects with PC and prostate hypertrophy that lead to PC. Studies in the past have noted that high concentrations of activating ligands with testosterone can suppress the growth of PC cells [2]. 

The goal of this study was to determine if nonsteroidal and orally bioavailable SARMs could achieve the same effect. This study was conducted both in vitro and in vivo [2].

The study found that the administration of SARMs did, in fact, suppress the growth of PC cells. The comparison to steroidal androgens was favorable [2]. Due to the fact that SARMs have already been tested in various clinical settings for other health conditions, the potential for accelerating them as a PC aid and implementing them, is available [2]. Preclinical and clinic development must continue in the future to replicate the findings of this study. 

The current study supports more exploration into using SARMs to assist PC. Clinic development needs to continue to explore and duplicate these findings, and include benign prostatic hyperplasia subjects to expand it’s reach [2]. In the future, testing on prostate-specific antigens should be studied related to their effects.

Cancer Cachexia Study: A muscle wasting disease

Cancer-associated cachexia currently lacks any approved therapy which is similar to muscle wasting in cancer patients. A recent study utilized the colon-26 mouse model, which effectively mimics recent late-stage clinical failures of anabolic anti-cachexia treatments in the hopes of finding reliable clinical applications to treat this disease [6].

Surprisingly, this model showed resistance to various androgen-based therapies, including the androgen receptor modulators SARMs GTx-024. However, the researchers found that the histone deacetylase inhibitor (HDACi) AR-42 exhibited significant anti-cachectic activity in this context [6].

Motivated by these findings, the researchers investigated the potential of combined SARM/AR-42 and its potential for cancer related cachexia. While reduced AR-42 provided limited anti-cachectic benefits, the combination of AR-42 with GTx-024 resulted in significant improvements in body weight, hindlimb muscle mass, and grip strength compared to control groups [6].

The team observed that AR-42 effectively suppressed the IL-6/GP130/STAT3 signaling axis in muscle tissue without affecting circulating cytokine levels. Furthermore, the administration of GTx-024 alone led to the regulation of β-catenin target genes specifically in cachectic mice when combined with AR-42 which prevented muscle wasting [6].

The data indicates that the cachectic signaling in this model involves catabolic pathways that are unresponsive to the anabolic therapy provided by GTx-024. Moreover, GTx-024-mediated anabolic signaling is hindered in the absence of AR-42 [6]. 

By mitigating catabolic gene activation and restoring anabolic effects and responsiveness to GTx-024, AR-42 offers a promising approach to improve the anabolic benefits such as the anabolic response in cachectic mammals [6].

In conclusion, combining GTx-024, a clinically established anabolic therapy, with AR-42, a clinically evaluated HDACi, holds great potential for enhancing the anabolic response in cachectic mammals [6].

SARMs and Other Medical Conditions

Further studies have looked even more closely at the use of SARMs when it comes to a variety of medical conditions. These studies continue to explore the potential of clinical trials related to SARMs.

Stress Urinary Incontinence (SUI)

A study on selective androgen receptor modulators and SUI was completed utilizing ovariectomized mice. Specifically, the SARM, GSK2849446A, was utilized [3]. 

Researchers looked at urethral continence function during a sneeze reflex. Female rats were used that had an ovariectomy-induced estrogen deficiency [3].  

The results of this study were favorable. The treatment groups found that SARMS could treat SUI without affecting the function of the bladder [3]. 

They do this by enhancing striated and smooth muscle-mediated urethral functions during conditions that cause stress, like sneezing [3]. 

Sarcopenia

Sarcopenia is a degenerative disease where subjects affected lose muscle mass over time. This muscle loss can lead to muscle dysfunction and reduced muscle strength [3]. 

Sarcopenia is generally present in elderly subjects and can impact their quality of life. A study in 2021 looked at multiple modes of this disease and how they could aid subjects with sarcopenia [3]. 

SARMs are one mode that were explored. Because SARMs have significant anabolic activities in bone and muscle, but moderate to minimal androgenic side effects, there are a few SARMs that have the potential to assist sarcopenia [3]. 

Some of the SARMs in question include [3]:

  • Ostarine
  • MK‐677
  • RAD-140
  • GSK2881078

 SARMs and Skeletal Muscle Research

One of the most frequently misused steroid precursors (prohormones) is 19-norandrostenedione (4-estrene-3,17-dione, NOR). After oral administration, it is readily metabolized to nortestosterone, also known as nandrolone (durabolin) [7]. 

In the present study, the molecular mechanisms of action of NOR were characterized, its tissue-specific androgenic and anabolic potency were determined following subcutaneous (s.c.) administration, and potential adverse effects were investigated [7]. 

The binding tests revealed that NOR exhibited high selectivity for the androgen receptor (AR). Its ability to transactivate AR-dependent reporter gene expression was found to be 10 times lower than that of dihydrotestosterone (DHT) [7]. 

After subcutaneous administration, the prohormone 19-norandrostenedione exhibits distinctive properties akin to selective androgen receptor modulators (SARMs) [7].

In vivo experiments using orchiectomized rats showed that s.c. treatment with NOR only stimulated the weight of the levator ani muscle, while the weights of the prostate and seminal vesicles remained unaffected [7]. 

Similar to testosterone, NOR administration resulted in increased AR and myostatin mRNA expression in the gastrocnemius muscle. NOR did not affect prostate proliferation, liver weight, or the expression of the tyrosine aminotransferase gene (TAT) in the liver [7].

In summary, the data clearly indicate that NOR, when administered s.c. and in contrast to its metabolite nandrolone, selectively stimulates the growth of skeletal muscle while exhibiting weak androgenic properties. This observation holds potential therapeutic relevance as well as implications for future prevention [7].

Another Study On Skeletal Muscles

A recent review explores the relationship between actin cytoskeletal components and androgen signaling, specifically in skeletal muscle, using test subjects and animal models [8].

Activation of the androgen receptor (AR) by androgens has been found to affect myoblast proliferation, sexual dimorphic muscle development, and muscle fiber type. In clinical settings, anabolic androgens have shown potential in reducing cachexia and promoting wound healing [8]. 

During the formation and regeneration of skeletal muscle, the actin cytoskeleton undergoes rearrangement, leading to the formation of myotubes and myofibrils [8]. 

Contraction of skeletal muscle coordinates signals between the neuromuscular junction and intra-myofibrils through costameres, functional structures associated with actin filaments that play a role in muscular dystrophy [8].

The discovery of actin-binding proteins acting as AR coregulators suggests a tight regulation of androgen signaling during skeletal muscle development and regeneration. Further research aims to identify SARMs that target skeletal muscle specifically, allowing for the engineering of a SARM-AR complex that recruits these coregulators selectively [8].

SARMs Studies and Safety

One of the more controversial topics when it comes to SARMs is their safety. While SARMs are encouraged for clinical trials and you can find a lot of information about SARMs online, are they safe? 

In addition, does it matter where you buy SARMs? The research below looked at the answers to questions researchers may have on where to buy SARMs. 

Buying SARMs For Your Research Needs

When buying SARMs for research, you want to know that they are properly labeled and will give you the intended results for your data. One study took the time to look at various SARMs available to get purchased in the UK and their labeling [5]. 

They took 20 different products and explored whether the reported ingredients were consistent with what was actually found in the bottle. For many bottles, they found that the ingredients listed on the bottle were not actual present inside the products. Reversely, they noted that ingredients in the product were not on the label [5]. 

For example, one bottle listed the ingredients as RAD-140 and Ibutamoren. However, when tested, the capsules did not contain RAD-140, but they did contain YK-11; a compound not listed [5]. 

Only six of the SARMs out of 20 actually contained the ingredients they reported and nothing else. If you buy SARMs, buying them from a trusted source is imperative [5].

If not, you might not actually know what you are getting. For example, a lot of SARMs companies also falsely label these compounds as dietary supplements, which they are not. They are research chemicals for research use only.

Explore More Androgen Receptor Modulators SARMs Science

The SARMs studies listed above are just a few in comparison to the vast amount of research that is still getting completed about SARMs. Take the time to educate yourself and arm yourself with the knowledge you need to complete accurate and valid research.

When getting SARMs for research like Andarine S4Ostarine, and Cardarine, it’s important that you ensure you are getting what’s listed on the label. As well, ensure these research chemicals are not being advertised as dietary supplements because they are only approved for research purposes only.

Sports Technology Labs provides products that are high quality and get tested by a third party for 98 percent purity. Contact us today to discuss SARMs and find out the many benefits of purchasing through us.

Scientific References:

1. A First-in-Human Phase 1 Study of a Novel Selective Androgen Receptor Modulator (SARM), RAD140, in ER+/HER2- Metastatic Breast Cancer – PubMed (nih.gov) pubmed.ncbi.nlm.nih.gov/34565686

2. JCI – Selective androgen receptor modulators activate the canonical prostate cancer androgen receptor program and repress cancer growth www.jci.org/articles/view/146777#top

3. Effects of a Selective Androgen Receptor Modulator (SARM), GSK2849446A, on Stress Urinary Incontinence and Bladder Activity in Rats with Ovariectomy-induced Estrogen Deficiency (nih.gov) www.ncbi.nlm.nih.gov/pmc/articles/PMC7261644/

4. Feike, Y., Zhijie, L., & Wei, C. (2021). Advances in research on pharmacotherapy of sarcopenia. Aging Medicine4(3), 221-233.

5. Leaney, A. E., Beck, P., Biddle, S., Brown, P., Grace, P. B., Hudson, S. C., & Mawson, D. H. (2021). Analysis of supplements available to UK consumers purporting to contain selective androgen receptor modulators. Drug Testing and Analysis13(1), 122-127.

6. Liva, S. G., Tseng, Y. C., Dauki, A. M., Sovic, M. G., Vu, T., Henderson, S. E., … & Coss, C. C. (2020). Overcoming resistance to anabolic SARM therapy in experimental cancer cachexia with an HDAC inhibitor. EMBO molecular medicine12(2), e9910.

7. Diel, P., Friedel, A., Geyer, H., Kamber, M., Laudenbach-Leschowsky, U., Schänzer, W., … & Zierau, O. (2008). The prohormone 19-norandrostenedione displays selective androgen receptor modulator (SARM) like properties after subcutaneous administration. Toxicology letters, 177(3), 198-204.

8. Chisamore, M. J., Gentile, M. A., Dillon, G. M., Baran, M., Gambone, C., Riley, S., … & Alves, S. E. (2016). A novel selective androgen receptor modulator (SARM) MK-4541 exerts anti-androgenic activity in the prostate cancer xenograft R–3327G and anabolic activity on skeletal muscle mass & function in castrated mice. The Journal of steroid biochemistry and molecular biology163, 88-97.

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