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Selective androgen receptor modulators (SARM)

Aug. 27, 2019

Selective androgen receptor modulators (SARMs) are new kinds of experimental anabolic compounds still in their experimental stage. In comparison with conventional anabolic steroids, they accelerate muscle growth possibly with less adverse effects. [1] SARMs bind to the androgen receptors of the tissues, changing their structure and function. There are a number of different SARM compounds, differing from one another by their chemical structure. Likewise, the mechanisms for binding to the androgenic receptors vary depending on the compound. [1] The effects of SARMs resemble those of testosterone and anabolic steroids. Due to this, they are used in the field of medicine for the treatment of some diseases [2]. In the field of competitive sports, SARM compounds have been prohibited since 2008 [5].

Medical uses and mechanism of action

SARMs can be divided into steroid and non-steroid compounds. Steroid-based SARMs were developed from the chemical structure of the testosterone molecule. [3] Most SARMs developed thus far are non-steroid-based compounds, however [4]. Non-steroid-based SARMs were originally discovered as a result of work done by researchers at the University of Tennessee and subsequently a number of different structural classes were developed from these SARMSs.[3] Some examples of known non-steroid-based SARM preparations include Enobosarm (ostarine), Ligandrol (LGD-4033), Testolone (RAD-140), and Andarine (GTX-007 or S-4).

SARM mechanisms of action are still largely unknown since research on them began only recently. A number of mechanisms, which are confirmed for SERM tissue activity, are applicable to SARMs as well. They have the capacity to activate the androgen receptors in selected tissues; in other words, they act as tissue-selective agonists. In practice, they are used to pursue the effects of androgens with fewer adverse effects. Conventional androgen treatments pose risks, for example, to the heart, the liver, and the prostate gland. The assumption is that SARMs have the capacity to activate the androgen receptors in the muscles and the bones with minimal adverse effects. Research data on the safety and actual effects of SARMs is currently inadequate, however. [4]

SARMs are used and their potency is studied, for instance, in the treatment of osteoporosis, prostate cancer, breast cancer, hypogonadism, cachexia, Alzheimer’s disease, prostatic hyperplasia, and sexual function disorder. [1, 4] SARM development also seeks to remove the virilizing effects of androgens, whereupon the diseases mentioned above could be treated especially in the case of women without the strong virilizing effects associated with androgens. Nevertheless, testosterone treatment is currently the main form of treatment. [4]

Use as a doping substance

The anabolic effects of SARMs and the potentially lower risk of adverse effects make them attractive to fitness enthusiasts and athletes who are pursuing the growth of muscle mass or strength. Foreign online shops sell a variety of SARMs and dietary supplements that have SARMs or chemically similar substances added to them. [1] The safety assessment of SARMs is still in the early stages, however, and pharmaceutical substances ordered from abroad may contain impurities, which further increase the risks of use.

Adverse effects

Because thus far there are only a few studies in the effects of SARMs on humans, the adverse effects are not known very well. For example, SERMs have been similarly researched for decades already and their adverse effects are known better. [4]

Ligandrol (LGD-4033) and Enobosarm have been tested in therapeutic doses on humans with positive results. Muscle mass growth has been detected, without the adverse effects that are typical for androgens. [6, 7] Eczema, increased creatine phosphokinase after exertion, headache, and xerostomia occurred as adverse effects. In addition, the test group that had used Ligandrol exhibited a greater number of upper respiratory tract infections, but these were not regarded to be related to the medication. [7]

Because there are only a few studies conducted on humans thus far, no one can guarantee the safety and efficacy of SARMs. Recently, the European Medicines Agency (EMA) refused the marketing authorization for anamorelin due to its marginal effect on increasing muscle mass. Meanwhile, the Food and Drug Administration (FDA) of the United States issued a warning about SARMs-related risks, which reportedly include hepatotoxicity and various heart issues. The long-term effects of these substances on humans are not known either. [8] Nevertheless, SARMs seem to be a promising means of treatment for many diseases. Due to this, they should be studied further.

Ville Leskinen
Master of Health Sciences (MHSc)

[1] Solomon ZJ. Mirabal J, Mazur D, Kohn T, Lipshultz L, Pastuszak A. Selective Androgen Receptor Modulators: Current Knowledge and Clinical Applications. Sex Med Rev. 2018; 1-11.
[2] Rauhala P, Simula A. 2019. Dopingaineryhmät ja -menetelmät. Suomen Urheilun Eettinen Keskus.
[3] Bhasin S & Jasuja R. Selective Androgen Receptor Modulators (SARMs) as Function Promoting Therapies. Curr Opin Clin Nutr Metab Care. 2009; 12(3): 232–240.
[4] Narayanan R, Coss C, Dalton J. Development of selective androgen receptor modulators (SARMs). Molecular and Cellular Endocrinology. 2018; 465: 134-142.
[5] Geyer H, Schänzer W, Thevis M. Anabolic agents: recent strategies for their detection and protection from inadvertent doping. Br J Sports Med 2014;48:820–826.
[6] Basaria S, Collins L , Dillon L , Orwoll K, Storer T, Miciek R , Ulloor J , Zhang A, Eder R , Zientek H , Gordon G, Kazmi S , Sheffi eld-Moore M, Bhasin S. The Safety, Pharmacokinetics, and Effects of LGD-4033, a Novel Nonsteroidal Oral, Selective Androgen Receptor Modulator, in Healthy Young Men. Journal of Gerontology: 2013;68(1):87–95.
[7] Clark R, Walker AC, Andrews S, Turnbull P, Wald J, Magee M. Safety, pharmacokinetics and pharmacological effects of the selective androgen receptor modulator, GSK2881078, in healthy men and postmenopausal women. Br J Clin Pharmacol. 2017 83(10): 2179–2194.
[8] U.S Food & Drug Administration. 2017. FDA In Brief: FDA warns against using SARMs in body-building products.