SARMs – How They Work in The Human Body?

SARMs, which is an abbreviation of Selective Androgen Receptor Modulators is a class of drugs consisting of androgen receptor ligands. In chemistry, the word ‘ligand’ is used for a molecule or a substance which binds to another (mostly a metal). A ‘receptor’ is that part of the human cell which responds to substances specifically. In simple terms, every receptor type in the body has a particular shape and does not allow every chemical substance in the body to bind. This means every class of receptor recognises specific molecules. The ‘androgen receptors’ is a class of receptors on the cells of human body which is activated by the binding of androgenic hormones which include testosterone and dihydrotestosterone. The testosterone, a prime ligand for the androgenic receptors and a hormone produced by the male reproductive organs, the testes, has important functions in the body, few of which include maintenance of sexual function and development of sex organs (1). SARMs are intended to have the same effects as androgenic anabolic drugs such as steroids and hormones such as testosterone.

SARMs – When are They Required?

There are certain conditions in which the testosterone level in the body decline. This results in presentation of specific signs and symptoms associated with disruption of body functions due to testosterone deficiency. The levels of testosterone naturally goes down with the age. Therefore, older men are more likely to be suffering from low testosterone levels. However, few other conditions have been reported to cause low levels of this hormone. These include injury to the testes, chemotherapy or radiotherapy, kidney disease, liver disease, AIDS, hypogonadism (a condition characterised by negligible production of sex hormones), use of opioids and disorders of thyroid glands. (2).

The testosterone replacement therapy is a widely used treatment option for men with low testosterone levels. While the valuable effects of testosterone are infrequently disputed, there is a scarcity of the literature on the risks of testosterone use (3). A study stated that patients receiving long-term therapy with methyltestosterone had abnormal liver-function tests and abnormal liver scans (4). Another research stated that in older men with high prevalence of chronic disease, the application of a testosterone gel was associated with an increased risk of cardiovascular adverse events (5). However, few other studies have quoted controversial statements. If the association of testosterone therapy with prostate cancer is chalked out, there are again controversial statements quoted in different researches. To cut short, in men undergoing this therapy and have been previously treated for high-risk prostate cancer, this therapy should be reconsidered (3).

The development of SARMs and research being done on this class of drugs in comparison with testosterone therapy provide an insight to the attractive outcomes according to which, SARMs, due to their selective nature, can be the source of positive effects similar to testosterone and specifically on muscles and bones, without any toxic effects on other organs of the body (1). The potential of SARMs is that they can maximize the positive attributes of steroidal androgens while minimizing negative effects, thereby providing therapeutic options for various diseases, including osteoporosis.

Low Risk of SARMs – Evidence-Based Statements:

  1. RAD-140 (Testolone): In an animal study (6), RAD-140 by Radius Health, Inc., also referred as ‘Testolone’, was evaluated for its efficacy and tolerability, it was stated that the drug, at a dose 10 times greater than the fully effective dose caused minimal rise of the liver enzymes. Furthermore, it was stated that the drug caused an increase in the muscle weight of experimental animals at a lower dose than that required to stimulate prostate weight increase. The authors concluded that,

“RAD-140 has excellent pharmacokinetics and is a potent anabolic in nonhuman primates as well. We believe the overall preclinical profile of RAD-140 is very good, and the compound has completed preclinical toxicology in both rats and monkeys.”

Another study in which the role of Testolone was discussed in context with treatment of Alzheimer disease, provided an understanding of the association with the low testosterone level and development of Alzheimer disease. The study assessed the effect of Testolone on brain and prostate glands of animals and the results proved the neuro-protective and prostate-protective effects of the drug (7).

  1. MK-2866 (Ostarine): Ostarine (Enobosarm, MK-2866 or GTx-024) is a nonsteroidal SARM that has been or is being studied in several phase II and phase III clinical trials in patients with cancer cachexia, sarcopenia, breast cancer, and stress urinary incontinence (8).

One of the chief effects of androgen deficiency is the disturbance in the lipid (fats) metabolism resulting in obesity and increased risk of type II diabetes (9). An animal study in which the effect of Ostarine was probed on the fat cells of rats and compared with testosterone, it was stated that the SARM drug regulated fat metabolism similarly to testosterone (10). A research published in 2016 also documented Ostarine to have significant impact on increasing muscle mass (11).

Low Cost of SARMs:

HGH (human growth hormone) which is responsible for the upregulation of growth in children and adolescents and specifically muscle and bone growth has been synthetically developed for treating case of poor growth. MK-677 or ibutamoren, another SARM, does the same by increasing the secretion of growth hormone. Interestingly, the receptors for ibutamoren in the brain are located in the region which controls mood, pleasure and cognition and therefore, the drug may have an effect on these areas too.

One way to enhance your HGH levels regardless of age, or other factors, is to use injectable HGH. The reported cost of injectable HGH was approximately $250 a month in till the year 2003. The current price has elevated since then. To condense this cost related talk, HGH can cost thousands of dollars a month. On the other hand, ibutamoren can be bought at a very reasonable price.

SARMs – Potent Anabolics:

The word ‘anabolic’ in medicine refers to building up. The anabolic effects of testosterone and synthetic drugs promote protein and collagen synthesis, and increase muscle size and bone metabolism. The anabolic to androgenic ratio of testosterone has been specified as a standard to be 1:1. The ratio is higher and reaches 30 for few other anabolic steroids. This ratio is different in SARMs and depend on the drug in this broad category. Preclinical animal studies peg LGD-4033’s anabolic to androgenic ratio at 500:1 which is quite significant and the figure itself remarks on the high anabolic potency of the LGD-4033, another drug from the SARMs category.

 

Canada Sarms RAD-140 (Testolone)

Canada Sarms MK-2866 (Ostarine)

Canada Sarms MK-677 (Ibutamoren)

Canada Sarms LGD-4033 (Ligandrol)

 

Sources/References

  1. Bhasin S, Jasuja R. Selective androgen receptor modulators as function promoting therapies. Curr Opin Clin Nutr Metab Care. 2009;12(3):232-40.
  2. Wang C, Jackson G, Jones TH, Matsumoto AM, Nehra A, Perelman MA, et al. Low Testosterone Associated With Obesity and the Metabolic Syndrome Contributes to Sexual Dysfunction and Cardiovascular Disease Risk in Men With Type 2 Diabetes. Diabetes Care. 2011;34(7):1669-75.
  3. Osterberg EC, Bernie AM, Ramasamy R. Risks of testosterone replacement therapy in men. Indian J Urol. 2014;30(1):2-7.
  4. Westaby D, Ogle SJ, Paradinas FJ, Randell JB, Murray-Lyon IM. Liver damage from long-term methyltestosterone. Lancet (London, England). 1977;2(8032):262-3.
  5. Basaria S, Coviello AD, Travison TG, Storer TW, Farwell WR, Jette AM, et al. Adverse events associated with testosterone administration. The New England journal of medicine. 2010;363(2):109-22.
  6. Miller CP, Shomali M, Lyttle CR, O’Dea LSL, Herendeen H, Gallacher K, et al. Design, Synthesis, and Preclinical Characterization of the Selective Androgen Receptor Modulator (SARM) RAD140. ACS Med Chem Lett. 2010;2(2):124-9.
  7. Jayaraman A, Christensen A, Moser VA, Vest RS, Miller CP, Hattersley G, et al. Selective androgen receptor modulator RAD140 is neuroprotective in cultured neurons and kainate-lesioned male rats. Endocrinology. 2014;155(4):1398-406.
  8. Komrakova M, Furtwangler J, Hoffmann DB, Lehmann W, Schilling AF, Sehmisch S. The Selective Androgen Receptor Modulator Ostarine Improves Bone Healing in Ovariectomized Rats. Calcified tissue international. 2019.
  9. Kelly DM, Akhtar S, Sellers DJ, Muraleedharan V, Channer KS, Jones TH. Testosterone differentially regulates targets of lipid and glucose metabolism in liver, muscle and adipose tissues of the testicular feminised mouse. Endocrine. 2016;54(2):504-15.
  10. Leciejewska N, Pruszynska-Oszmalek E, Bien J, Nogowski L, Kolodziejski PA. Effect of ostarine (enobosarm/GTX024), a selective androgen receptor modulator, on adipocyte metabolism in Wistar rats. Journal of physiology and pharmacology : an official journal of the Polish Physiological Society. 2019;70(4).
  11. Molfino A, Amabile MI, Rossi Fanelli F, Muscaritoli M. Novel therapeutic options for cachexia and sarcopenia. Expert opinion on biological therapy. 2016;16(10):1239-44.