Selective androgen receptor modulator explained

Synonyms:Nonsteroidal androgen (although not all SARMs are nonsteroidal)
Use:Investigational
Biological Target:Androgen receptor
Chemical Class:Mostly nonsteroidal
Legal Us:Investigational New Drug
Legal Au:Schedule 4
Legal Au Comment:[1]

Selective androgen receptor modulators (SARMs) are a class of drugs that selectively activate the androgen receptor in specific tissues, promoting muscle and bone growth while having less effect on male reproductive tissues like the prostate gland.

Non-selective steroidal drugs, called anabolic androgenic steroids (AAS), have been used for various medical purposes, but their side effects limit their use. In 1998, researchers discovered a new class of non-steroidal compounds, the SARMs. These compounds selectively stimulate the androgen receptor, offering potent effects on bone and muscle to increase bone density and lean body mass while having minimal impact on reproductive tissues.

SARMs have been investigated in human studies for the treatment of osteoporosis, cachexia (wasting syndrome), benign prostatic hyperplasia, stress urinary incontinence, and breast cancer., there are no SARMs which have been approved by the United States Food and Drug Administration or the European Medicines Agency. Although adverse effects in clinical studies have been infrequent and mild, SARMs can cause elevated liver enzymes, reduction of HDL cholesterol levels, and hypothalamic–pituitary–gonadal axis (HPG axis) suppression, among other side effects.

Since the early twenty-first century, SARMs have been used in doping; they were banned by the World Anti-Doping Agency in 2008. SARMs are readily available on internet-based gray markets and are commonly used recreationally to stimulate muscle growth.

History

Steroidal androgens

Anabolic androgenic steroids (AAS) are used to treat a variety of medical conditions, but their side effects have fueled a search for a new class of drugs, with a better separation between desirable anabolic and undesirable androgenic effects. The first clinically used AAS was testosterone which was discovered in 1935 and first approved for medical use in 1939.[2] AAS including those produced endogenously such as testosterone and dihydrotestosterone (DHT), bind to and activate the androgen receptor (AR) to produce their effects. AAS effects can be separated into androgenic (the development and maintenance of male sexual characteristics) and anabolic (increasing bone density, muscle mass and strength). AAS also affect hematopoiesis, coagulation, metabolism, and cognition.[3] For most medical applications, an AAS with potent anabolic and minimal androgenic and cardiovascular effects would be an advantage.

In the 1930s, 17α-alkylated anabolic steroids were discovered. These have increased metabolic stability and are orally active, but are not tissue selective. These alkylated anabolic steroids still have significant androgenic effects, and are also hepatotoxic.[4] In 1950, nandrolone (19-nortestosterone) was first synthesized, which is sometimes considered a SARM due to greater tissue selectivity than testosterone.[5] [6] [7] In addition, 7α-alkyl substitution of testosterone (for example trestolone) has also been reported to increase its anabolic effects. However, efforts to develop a steroid with anabolic but minimal androgenic effects were not successful.[8]

SERMs

Interest in nonsteroidal AR mixed agonists/antagonists increased after the therapeutic uses of selective estrogen receptor modulators (SERMs) became evident. The first SERM, tamoxifen, was originally developed as an anti-estrogen contraceptive. However, it was discovered it promoted ovulation in humans by acting as an agonist in ovaries. The drug was then successfully repurposed as a treatment for breast cancer where it was found to act as a full antagonist in breast tissue.[9] Somewhat unexpectedly, it was also discovered that tamoxifen preserves bone density[10] by acting as an agonist in bone resorbing osteoclasts.[11] The clinical success of SERMs stimulated interest in analogous tissue selective drugs that target the AR.

Non-steroidal AR antagonists

The chemical starting point for AR mixed agonist/antagonists were nonsteroidal AR antiandrogens such as flutamide, nilutamide, bicalutamide. These antagonists work by binding to the AR to prevent androgenic action; this class of chemicals dates to the 1970s.[12] The discovery of arylpropionamides, which share structural similarity with bicalutamide and hydroxyflutamide, suggested a way to make compounds that bind to the AR and produce both anabolic and antiandrogenic effects. Selective androgen receptor modulators (SARMs) were developed out of a desire to maintain the anabolic effects of androgens on muscle and bone, while avoiding side effects on other tissues such as the prostate and cardiovascular system.

Non-steroidal SARMs

The first non-steroidal SARMs were developed in 1998 independently by two research groups, one at the University of Tennessee that created an arylpropionamide SARM and Ligand Pharmaceuticals that made a SARM with a quinolone core structure. The name was adopted by analogy with SERMs. Other SARMs include tetrahydroquinolines, tricyclics, bridged tricyclics, aniline, diaryl aniline, bicylclic hydantoins, benzimidazole, imidazolopyrazole, indole, and pyrazoline derivatives.[13] SARMs can be agonists, antagonists, or partial agonists of the AR depending on the tissue, which can enable targeting specific medical conditions while minimizing side effects. Those that have advanced to human trials show stronger effects in bone and muscle tissue and weaker effects in the prostate.

Unlike most current forms of testosterone replacement, SARMs are orally bioavailable and largely eliminated via hepatic metabolism and metabolized through amide hydrolysis in the case of arylpropionamides and A-ring nitro reduction of andarine.

Proposed treatment of hypogonadism

Because of the potentially better side effect profile of SARMs compared to testosterone, SARMs have been proposed for use in the treatment of hypogonadism and for androgen replacement therapy.[14] Phase I and II trials have provided preliminary evidence that the SARMs enobosarm and GSK-2881078 (in elderly men and postmenopausal women), and OPL-88004 (prostate cancer survivors with low levels of testosterone) increase lean body mass and muscle size with little effect on the prostate, supporting the potential of SARMs for use in hormone replacement therapy. However, it has been argued that SARMs are not ideal for use in androgen replacement therapy and could not replace testosterone in this context as they do not reproduce testosterone's full spectrum of effects, including androgenic potentiation via 5α-reduction and aromatization into estrogen.[15] Estrogenic signaling in particular is essential for normal male physiology and health, including for instance maintenance of bone strength.[16] [17]

Mechanism

The mechanism of action of SARMs' tissue-specific effects continues to be debated . A number of hypotheses have been advanced. These include the non-activation of SARMs by 5α-reductase, tissue selective expression of androgen receptor coregulators, non-genomic signaling, and tissue selective uptake of SARMs.

5α-Reductase

Testosterone is active in non-reproductive tissue without activation. In contrast, tissue selective activation by 5α-reductase to the more active form DHT is required for significant activity in reproductive tissue. The net result is that testosterone and its metabolite together are not tissue selective.[18] SARMs are not substrates of 5α-reductase, hence they are not selectively activated like testosterone in tissues such as prostate. This lack of activation effectively imparts a degree of tissue selectivity to SARMs.[19]

Androgen receptor coregulators

Tissue selective transcription coregulator expression is another possible contributor to the selectivity of SARMs. Like other type I nuclear receptors, the unliganded androgen receptor (AR) resides in the cytosol complexed with heat shock proteins (HSP). Upon ligand binding, the AR freed from HSPs and translocated into the nucleus where it binds to androgen response elements on DNA to regulate gene expression.[20] AR agonists such as testosterone recruit coactivator proteins to AR that facilitate upregulation of gene expression while antagonists recruit corepressors which down regulate gene expression. Furthermore, the ratio of coactivators to corepressors is known to vary depending on tissue type.[21] Structurally, pure AR agonists stabilize the position of helix-12 (H12) in the ligand binding domain of AR near H3 and H4 to produce a surface cleft that binds to a FxxLF motif contained in coactivators. Conversely, antagonists destabilize the agonist conformation of H12 blocking the binding of the FXXLF coactivator motif while facilitating the binding of the corepressor LXX(I/H)IXXX(I/L) motif found in NCOR1 and SMRT corepressors.

In analogy to SERMs, SARMs are mixed agonists/antagonists displaying agonist androgen receptor activity in bone and muscle and partial agonist or antagonist activity in other tissues such as prostate. Non-selective agonists such as testosterone are able to recruit coactivators when bound to AR but not corepressors and hence are agonists in all tissues. In contrast, SARMs can recruit both coactivators and corepressors by partially destabilizing the agonist conformation of H12. In tissues where coactivators are in excess (as in bone and muscle), SARMs act as agonists. Conversely, in tissues where corepressors are in excess (such as prostate), SARMs act as partial agonists or antagonists.

In vitro testing of the SARMs enobosarm (ostarine) and YK-11 showed that they bound to the AR, but unlike full AR agonists, they blocked interaction between the N-terminus and C-terminus of AR which resulted in a mixed agonist/antagonist mode of action.[22]

Non-genomic signaling

In addition to the regulation of gene expression by nuclear AR, membrane associated AR is known to have rapid non-genomic effects on cells through signal transduction cascades. Non-genomic effects appear to significantly contribute to the anabolic effects of androgens whereas genomic effects are primarily responsible for the development of male sexual organs. Furthermore, each steroidal androgen or non-steroidal SARM uniquely influences distinct pathways depending on cell type.

Tissue distribution

Tissue selective uptake into anabolic tissues presents another potential mechanism for SARM tissue selectivity. However autoradiography studies with radiolabeled SARMs show no preferential distribution to anabolic tissues.

Drug candidates

SARM drug candidates
NameClassDeveloperInvestigated forHighest development stage reachedStructure
Andarine (S-4, GTx-007) Arylpropionamide GTx, Oncternal Therapeutics Cachexia[23] Phase I (discontinued)
Arcarine (ORM-11984)[24] Unknown Benign prostatic hyperplasia, hypogonadism, osteoporosis Phase I (discontinued) Structure undisclosed
DT-200 (GLPG-0492) Imidazolidine-2,4-dione ProSkelia, Akashi Therapeutics, Galapagos NV[25] Muscular dystrophy, cachexia Phase I[26]
Enobosarm (ostarine, GTx-024, MK-2866, S-22) Arylpropionamide GTx, Veru Healthcare[27] Phase III[28]
Unknown GlaxoSmithKline[29] Sarcopenia Phase I (discontinued)[30] Structure undisclosed
Unknown GlaxoSmithKline[31] Cachexia, heart failure Phase I (discontinued)[32] Structure undisclosed
GSK-2881078Indole GlaxoSmithKline[33] Cachexia[34] Phase II[35]
LGD-2941 (LGD-122941) Quinolinone Ligand Pharmaceuticals[36] Cachexia, sexual dysfunction, hypogonadism, menopause, osteoporosis Phase I (discontinued)
Pyrrolidinebenzonitrile Muscle wasting due to hip fracture, cachexia, hypogonadism, osteoporosis[37] Phase II[38]
LY305N-arylhydroxyalkyl Osteoporosis[39] Phase I
MK-0773 (PF-05314882) GTx, Merck[40] Sarcopenia, osteoporosis Phase II (discontinued)[41] [42]
Benzylpropionamide Sarcopenia Phase I
OPK-88004 (LY-2452473, TT-701) Benign prostatic hyperplasia, quality of life in prostate cancer, erectile dysfunction[43] [44] Phase II[45]
Isoquinoline Pfizer[46] [47] Cachexia Phase I (discontinued)
Unknown Bristol-Myers Squibb, Ligand Pharmaceuticals[48] Andropause, cachexia Phase I (discontinued)[49] Structure undisclosed
Vosilasarm (RAD140, EP0062, testolone) Phenyloxadiazole Ellipsis Breast cancer, osteoporosis, sarcopenia[50] Phase I/II[51]
Muscle wasting[52] data-sort-value="Phase 0" Preclinical

Certain anabolic steroids, like trestolone, dimethandrolone undecanoate, and 11β-methyl-19-nortestosterone dodecylcarbonate, have also sometimes been classified as SARMs.

Possible therapeutic applications

Due to their tissue selectivity, SARMs have the potential to treat a wide variety of conditions, including debilitating diseases. They have been investigated in human studies for the treatment of osteoporosis, cachexia, benign prostatic hyperplasia, stress urinary incontinence, prostate cancer, and breast cancer and have also been considered for the treatment of Alzheimer's disease, Duchenne muscular dystrophy, hypogonadism and as a male contraceptive., there are no SARMs which have been approved for therapeutic use by the United States Food and Drug Administration or the European Medicines Agency.[53]

Most SARMs have been tested in vitro or on rodents, while limited clinical trials in humans have been carried out. Initial research focused on muscle wasting. Enobosarm (ostarine) is the most well-studied SARM; according to its manufacturer, GTx Incorporated, 25 studies have been carried out on more than 1,700 humans involving doses from 1 to 18 mg each day.[54], there is little research distinguishing different SARMs from each other. Much of the research on SARMs has been conducted by corporations and has not been made publicly available.

Benign prostatic hyperplasia

In rat models of benign prostatic hyperplasia (BPH), a condition where the prostate is enlarged in the absence of prostate cancer, SARMs reduced the weight of the prostate.[55] OPK-88004 advanced to a phase II trial in humans, but it was terminated due to difficulty in measuring prostate size, the trial's primary endpoint.

Cancer

SARMs may help treat AR and estrogen receptor (ER) positive breast cancer, which comprise the majority of breast cancers.[56] AAS were historically used successfully to treat AR positive breast cancer, but were phased out after the development of antiestrogen therapies, due to androgenic side effects and concerns about aromatization to estrogen (which does not occur with SARMs). Although a trial on AR positive triple negative breast cancer (which is ER-) was ended early due to lack of efficacy, enobosarm showed benefits in some patients with ER+, AR+ breast cancer in a phase II study. In patients with more than 40 percent AR positivity as determined by immunohistochemistry, the clinical benefit rate (CBR) was 80 percent and the objective response rate (ORR) was 48 percent—which was considered promising given that the patients had advanced disease and had been heavily pretreated.[57] In 2022, the FDA granted fast track designation to enobosarm for AR+, ER+, HER2- metastatic breast cancer.[58] Other SARMs such as vosilasarm have reached clinical trials in breast cancer patients.[59]

Bone and muscle wasting

, there are no drugs approved to treat muscle wasting in people with chronic diseases, and there is therefore an unmet need for anabolic drugs with few side effects. One aspect hindering drug approval for treatments for cachexia and sarcopenia (two types of muscle wasting) is disagreement in what outcomes would demonstrate the efficacy of a drug. Several clinical trials have found that SARMs improve lean mass in humans, but it is not clear whether strength and physical function are also improved. After promising results in a phase II trial, a phase III trial of enobosarm was proven to increase lean body mass but did not show significant improvement in function. It and other drugs have been refused regulatory approval due to a lack of evidence that they increased physical performance; preventing decline in functionality was not considered an acceptable endpoint by the Food and Drug Administration. It is not known how SARMs interact with dietary protein intake and resistance training in people with muscle wasting.[60] [61]

Phase II trials of enobosarm for stress urinary incontinence—considered promising, given that the levator ani muscle in the pelvic floor has a high androgen receptor density—did not meet their endpoint and were abandoned.

Unlike other treatments for osteoporosis, which work by decreasing bone loss, SARMs have shown potential to promote growth in bone tissue. LY305 showed promising results in a phase I trial in humans.

Side effects

In contrast to AAS and testosterone replacement, which have many side effects that have curtailed their medical use, SARMs are well tolerated and have mild and infrequent adverse events in randomized controlled trials. SARMs are sometimes claimed to be non-virilizing (non-masculinizing).[62] In actuality however, SARMs are largely uncharacterized clinically in terms of potential virilizing effects. In addition, SARMs cannot be aromatized to estrogen, thus causing no estrogenic side effects, for instance gynecomastia.

SARM use can cause elevated liver enzymes and reduction in HDL cholesterol. Transdermal administration via a skin patch may reduce these effects. Several case reports have associated SARMs with hepatocellular drug-induced liver injury when used recreationally, it is not known if the risk is significant for medical use. Whether SARMs increase the risk of cardiovascular events is unknown. SARMs have less effect on blood lipid profiles than testosterone replacement; it is not known whether androgen-induced HDL reductions increase cardiovascular risk; and SARMs increase insulin sensitivity and lower triglycerides.

Although they cause less suppression of the hypothalamic–pituitary–gonadal axis (HPG axis) than testosterone, studies have found that gonadotropins, free and total testosterone, and SHBG can be reduced in a compound- and dose-dependent fashion in men from SARM usage. Typically SHBG is reduced along with total testosterone and total cholesterol while hematocrit is increased. Most studies have found that follicle-stimulating hormone (FSH), luteinizing hormone (LH), prostate-specific antigen, estradiol, and DHT levels are not altered. Of SARMs that have been investigated, enobosarm is one of the least suppressive of gonadotropins, even in doses much higher than used in clinical trials. How the HPG axis is affected in women using SARMs is unknown. SARMs' effect in suppressing the gonadotropins FSH and LH is what makes SARMs potentially useful as a male contraceptive.[63]

Non-medical use

Outside of pharmaceutical research, SARMs are a gray market substance produced by small laboratories and often marketed as a research chemical supposedly not for human consumption.[64] [65] Marketing SARMs for human consumption is illegal in some jurisdictions and has led to criminal convictions in the United States[66] and the largest-ever fine levied under Australia's Therapeutic Goods Act 1989.[67] Although SARMs are readily available for purchase on the internet, one study found that a majority of products advertised as SARMs online were mislabeled. Anecdotes and guides on usage can also be found online and on social media.[68] Some compounds are commonly marketed for recreational use as SARMs despite having a different mechanism of action. These substances include ibutamoren (MK-677), which increases secretion of growth hormone; GW501516 (cardarine), an exercise mimetic that works as an agonist of the PPARβ/δ; and SR9009 (Stenabolic), an agonist of the Rev-Erb, which plays a role in circadian rhythm.[69]

SARMs are used by bodybuilders and competitive athletes due to their anabolic and lack of androgenic effects, particularly in the United States, Europe, and other western countries.[70] Some individuals using SARMs recreationally combine multiple SARMs or take a SARM along with other compounds, although there is no research on combining SARMs. The doses used often exceed those from clinical trials; nevertheless, the fat-free mass gained from SARMs is generally lower than what is obtained with moderate doses of testosterone derivatives. According to one study of SARM users, more than 90 percent were satisfied with their usage and 64 percent would take SARMs again even though a majority experienced adverse effects.[71]

SARMs were banned by the World Anti-Doping Agency (WADA) in 2008. SARMs can be detected in urine and hair after consumption.[72] WADA reported its first adverse analytical finding for SARMs in 2010 and the number of positive tests has increased since then; the most commonly detected SARMs are enobosarm (ostarine) and LGD-4033 (ligandrol).[73] [74] Athletes competing in the NFL, NBA, UFC, NCAA, and the Olympics have tested positive.[75] There is limited evidence on how SARMs affect athletic performance.[76]

Terminology

SARMs are sometimes also referred to as "nonsteroidal androgens",[77] [78] although not all SARMs are nonsteroidal in structure and steroidal SARMs also exist.[79] The first SARMs, discovered in 1998, were nonsteroidal and were initially called nonsteroidal androgens.[80] In 1999, the term "selective androgen receptor modulator" or "SARM" was introduced, as the mixed agonist–antagonist and tissue-selective activity of these nonsteroidal androgen receptor agonists had similarities with selective estrogen receptor modulators (SERMs).[81] Despite its widespread use, the term "selective androgen receptor modulator" has been criticized by some authors, like David Handelsman, who argue that it is a misleading pharmaceutical marketing term rather than an accurate pharmacological description.[82] He has also critiqued notions that SARMs isolate anabolic effects from androgenic or virilizing effects, as has been previously claimed in the case of anabolic steroids.[83] [84] [85]

Notes and References

  1. News: Koh . Benjamin . Anti-doping agency warns cheats on the health risks of Endurobol . 4 September 2023 . The Conversation . 22 March 2013 . en . 4 September 2023 . https://web.archive.org/web/20230904215336/https://theconversation.com/anti-doping-agency-warns-cheats-on-the-health-risks-of-endurobol-12997 . live .
  2. Book: Brannigan RE . Testosterone Therapy and Male Fertility . Mulhall JP, Maggi M, Trost L . Controversies in Testosterone Deficiency . 2021 . Springer International Publishing . 978-3-03-077111-9 . 57–70 (57) . 10.1007/978-3-030-77111-9_6 . 237993949 .
  3. Solomon . Zachary J. . Mirabal . Jorge Rivera . Mazur . Daniel J. . Kohn . Taylor P. . Lipshultz . Larry I. . Pastuszak . Alexander W. . Selective Androgen Receptor Modulators: Current Knowledge and Clinical Applications . Sexual Medicine Reviews . 2019 . 7 . 1 . 84–94 . 10.1016/j.sxmr.2018.09.006. 30503797 . 6326857 .
  4. Bhasin . Shalender . Krishnan . Venkatesh . Storer . Thomas W . Steiner . Mitchell . Dobs . Adrian S . Androgens and Selective Androgen Receptor Modulators to Treat Functional Limitations Associated With Aging and Chronic Disease . The Journals of Gerontology: Series A . 2023 . 78 . Supplement_1 . 25–31 . 10.1093/gerona/glad027 . 37325955 . 10272983 . September 1, 2023 . September 1, 2023 . https://web.archive.org/web/20230901195718/https://academic.oup.com/biomedgerontology/article/78/Supplement_1/25/7199272#408664293 . live .
  5. Book: Jasuja . Ravi . Zacharov . Mikhail N. . Bhasin . Shalender . The state-of-the-art in the development of selective androgen receptor modulators . 10.1017/CBO9781139003353.022 . Nieschlag E, Behre HM . Testosterone: Action, Deficiency, Substitution . 2012 . Cambridge University Press . 978-1-107-01290-5 . 459–460 . 4th . .
  6. Bhasin . Shalender . Jasuja . Ravi . Selective Androgen Receptor Modulators (SARMs) as Function Promoting Therapies . Current Opinion in Clinical Nutrition and Metabolic Care . 2009 . 12 . 3 . 232–240 . 10.1097/MCO.0b013e32832a3d79 . 19357508 . 2907129 . 1363-1950.
  7. Book: Thevis M, Schänzer W . Synthetic Anabolic Agents: Steroids and Nonsteroidal Selective Androgen Receptor Modulators . Doping in Sports . Handbook of Experimental Pharmacology . 195. 195 . 99–126 . 2010 . 20020362 . 10.1007/978-3-540-79088-4_5 . 978-3-540-79087-7 . One of the first synthetic analogs to testosterone prepared by the Noble laureate Ruzicka was 17α-methyltestosterone (Ruzicka et al. 1935)..
  8. Book: Katzung . Bertram G. . Basic and Clinical Pharmacology . 14th . 2017 . McGraw Hill Professional . 978-1-259-64116-9 . 741 . en.
  9. Quirke VM . Tamoxifen from Failed Contraceptive Pill to Best-Selling Breast Cancer Medicine: A Case-Study in Pharmaceutical Innovation . Frontiers in Pharmacology . 8 . 620 . 2017 . 28955226 . 5600945 . 10.3389/fphar.2017.00620 . free .
  10. Jordan VC . Turning scientific serendipity into discoveries in breast cancer research and treatment: a tale of PhD students and a 50-year roaming tamoxifen team . Breast Cancer Research and Treatment . 190 . 1 . 19–38 . November 2021 . 34398352 . 8557169 . 10.1007/s10549-021-06356-8 .
  11. Book: Komm BS, Cheskis B, Bodine PV . Regulation of Bone Cell Function by Estrogens . Marcus R . Osteoporosis . November 2007 . Elsevier Science . 978-0-08-055347-4 . 383–412 (409) . https://books.google.com/books?id=blFlkDHffW8C&dq=Tamoxifen+osteoclast&pg=PA409 . 2024-02-04 . 2024-03-08 . https://web.archive.org/web/20240308031542/https://books.google.com/books?id=blFlkDHffW8C&dq=Tamoxifen+osteoclast&pg=PA409#v=onepage&q=Tamoxifen%20osteoclast&f=false . live .
  12. Temerdashev . A. Z. . Dmitrieva . E. V. . Methods for the Determination of Selective Androgen Receptor Modulators . Journal of Analytical Chemistry . 2020 . 75 . 7 . 835–850 . 10.1134/S1061934820070187. 220398030 .
  13. Machek . Steven B. . Cardaci . Thomas D. . Wilburn . Dylan T. . Willoughby . Darryn S. . Considerations, possible contraindications, and potential mechanisms for deleterious effect in recreational and athletic use of selective androgen receptor modulators (SARMs) in lieu of anabolic androgenic steroids: A narrative review . Steroids . 2020 . 164 . 108753 . 10.1016/j.steroids.2020.108753 . 33148520 . 225049089 . 0039-128X . Sex-specific SARM effects on humans also remain considerably nebulous. SARMs may represent a more tempting option for female recreational use given potential previous tendencies towards less androgenic AAS (i.e. oxandrolone) [103]. Regardless, as the latter still imposes risk for permanent masculinization and hepatotoxicity, SARMs are largely uncharacterized for female-specific impacts. . 2023-08-30 . 2023-08-30 . https://web.archive.org/web/20230830031101/https://www.sciencedirect.com/science/article/abs/pii/S0039128X20301793 . live .
  14. Book: Zaveri NT, Murphy BJ . Nuclear hormone receptors . A SARM for the treatment of hypogonadism or osteoporosis would be an AR agonist in the muscle and bone, with minimal hypertrophic agonist effects in the prostate. . Taylor JB, Triggle DJ . Comprehensive Medicinal Chemistry II . Elsevier . 2007 . 993–1036 . 10.1016/B0-08-045044-X/00063-8 . 9780080450445 .
  15. Androgen Physiology, Pharmacology, Use and Misuse . Endotext . 5 October 2020 . 25905231 . Feingold KR, Anawalt B, Blackman MR, Boyce A, Chrousos G, Corpas E, De Herder WW, Dhatariya K, Dungan K, Hofland J, Kalra S, Kaltsas G, Kapoor N, Koch C, Kopp P, Korbonits M, Kovacs CS, Kuohung W, Laferrère B, Levy M, McGee EA, McLachlan R, New M, Purnell J, Sahay R, Shah AS, Singer F, Sperling MA, Stratakis CA, Trence DL . These features suggest that non-steroidal androgens have potential for development into pharmacologic androgen therapy regimens as tissue-selective mixed or partial androgen agonists (“selective androgen receptor modulators”, SARM) (419, 718). Conversely, they are not ideal for androgen replacement therapy where the full spectrum of testosterone effects including aromatization is idealy required, especially for tissues such as the brain (148, 159) and bone (153) where aromatization is a prominent feature of testosterone action..
  16. Russell N, Grossmann M . Mechanisms in Endocrinology: Estradiol as a male hormone . Eur J Endocrinol . 181 . 1 . R23–R43 . July 2019 . 31096185 . 10.1530/EJE-18-1000 .
  17. Cooke PS, Nanjappa MK, Ko C, Prins GS, Hess RA . Estrogens in Male Physiology . Physiol Rev . 97 . 3 . 995–1043 . July 2017 . 28539434 . 6151497 . 10.1152/physrev.00018.2016 .
  18. Kicman AT . Pharmacology of anabolic steroids . British Journal of Pharmacology . 154 . 3 . 502–521 . June 2008 . 18500378 . 2439524 . 10.1038/bjp.2008.165 .
  19. Gao W, Dalton JT . Ockham's razor and selective androgen receptor modulators (SARMs): are we overlooking the role of 5α-reductase? . Molecular Interventions . 7 . 1 . 10–3 . February 2007 . 17339601 . 2040232 . 10.1124/mi.7.1.3 .
  20. Tan MH, Li J, Xu HE, Melcher K, Yong EL . Androgen receptor: structure, role in prostate cancer and drug discovery . Acta Pharmacologica Sinica . 36 . 1 . 3–23 . January 2015 . 24909511 . 4571323 . 10.1038/aps.2014.18 .
  21. Smith CL, O'Malley BW . Coregulator function: a key to understanding tissue specificity of selective receptor modulators . Endocrine Reviews . 25 . 1 . 45–71 . February 2004 . 14769827 . 10.1210/er.2003-0023 . free .
  22. Narayanan R, Coss CC, Dalton JT . Development of selective androgen receptor modulators (SARMs) . Molecular and Cellular Endocrinology . 465 . 134–142 . April 2018 . 28624515 . 5896569 . 10.1016/j.mce.2017.06.013 .
  23. Web site: Andarine . AdisInsight . Springer Nature Switzerland AG . 2024-01-03 . 2024-01-03 . https://web.archive.org/web/20240103223409/https://adisinsight.springer.com/drugs/800019485 . live .
  24. Web site: Arcarine . Synapse . PatSnap . 2024-01-14 . 2024-01-14 . https://web.archive.org/web/20240114011909/https://synapse.patsnap.com/drug/3c0a1cb1cbc14552b622c39a85ef56fd . live .
  25. Web site: DT 200 . AdisInsight . Springer Nature Switzerland AG . 2024-01-14 . 2024-01-03 . https://web.archive.org/web/20240103033205/https://adisinsight.springer.com/drugs/800018432 . live .
  26. Web site: GLPG0492 Intervention/Treatment Search Results . ClinicalTrials.gov . U.S. National Library of Medicine . 2024-02-08 . 2024-02-08 . https://web.archive.org/web/20240208092050/https://clinicaltrials.gov/search?intr=GLPG0492&viewType=Table . live .
  27. Web site: Enobosarm - Veru Healthcare . AdisInsight . Springer Nature Switzerland AG . 2024-01-14 . 2023-04-05 . https://web.archive.org/web/20230405044358/https://adisinsight.springer.com/drugs/800022562 . live .
  28. Web site: Enobosarm Intervention/Treatment Search Results . ClinicalTrials.gov . U.S. National Library of Medicine . 2024-02-11 . 2024-03-08 . https://web.archive.org/web/20240308031552/https://clinicaltrials.gov/search?intr=Enobosarm&viewType=Table . live .
  29. Web site: GSK 971086 . AdisInsight . Springer Nature Switzerland AG . 2024-01-14 . 2024-01-14 . https://web.archive.org/web/20240114011909/https://adisinsight.springer.com/drugs/800027354 . live .
  30. Web site: GSK971086 Intervention/Treatment Search Results . ClinicalTrials.gov . U.S. National Library of Medicine . 2024-02-11 . 2024-03-08 . https://web.archive.org/web/20240308031540/https://clinicaltrials.gov/search?intr=GSK971086&viewType=Table . live .
  31. Web site: GSK 2849466 . AdisInsight . Springer Nature Switzerland AG . 2024-01-14 . 2024-01-14 . https://web.archive.org/web/20240114011909/https://adisinsight.springer.com/drugs/800036899 . live .
  32. Web site: GSK2849466 Intervention/Treatment Search Results . ClinicalTrials.gov . U.S. National Library of Medicine . 2024-02-11 . 2024-03-08 . https://web.archive.org/web/20240308031554/https://clinicaltrials.gov/search?intr=GSK2849466&viewType=Table . live .
  33. Web site: GSK 2881078 . AdisInsight . Springer Nature Switzerland AG . 2024-01-14 . 2024-01-03 . https://web.archive.org/web/20240103033122/https://adisinsight.springer.com/drugs/800039743 . live .
  34. Mohan . Divya . Rossiter . Harry . Watz . Henrik . Fogarty . Charles . Evans . Rachael A. . Man . William . Tabberer . Maggie . Beerahee . Misba . Kumar . Subramanya . Millns . Helen . Thomas . Sebin . Tal-Singer . Ruth . Russell . Alan J. . Holland . Marie Claire . Akinseye . Chika . Neil . David . Polkey . Michael I. . Selective androgen receptor modulation for muscle weakness in chronic obstructive pulmonary disease: a randomised control trial . Thorax . 1 March 2023 . 78 . 3 . 258–266 . 10.1136/thorax-2021-218360 . 36283827 . 9985744 . en . 0040-6376 . 11 September 2023 . 2 September 2023 . https://web.archive.org/web/20230902055836/https://thorax.bmj.com/content/78/3/258 . live .
  35. Web site: GSK2881078 Intervention/Treatment Search Results . ClinicalTrials.gov . U.S. National Library of Medicine . 2024-02-11 . 2024-03-08 . https://web.archive.org/web/20240308031549/https://clinicaltrials.gov/search?intr=GSK2881078&viewType=Table . live .
  36. Web site: LGD 2941 . AdisInsight . Springer Nature Switzerland AG . 2024-01-14 . 2024-01-14 . https://web.archive.org/web/20240114011910/https://adisinsight.springer.com/drugs/800013541 . live .
  37. Web site: VK 5211 . AdisInsight . Springer Nature Switzerland AG . 2024-01-07 . 2024-01-03 . https://web.archive.org/web/20240103033158/https://adisinsight.springer.com/drugs/800030373 . live .
  38. Web site: VK5211 Intervention/Treatment Search Results . ClinicalTrials.gov . U.S. National Library of Medicine . 2024-02-11 . 2024-03-08 . https://web.archive.org/web/20240308031540/https://clinicaltrials.gov/search?intr=VK5211&viewType=Table . live .
  39. Krishnan . V. . Patel . N. J. . Mackrell . J. G. . Sweetana . S. A. . Bullock . H. . Ma . Y. L. . Waterhouse . T. H. . Yaden . B. C. . Henck . J. . Zeng . Q. Q. . Gavardinas . K. . Jadhav . P. . Saeed . A. . Garcia-Losada . P. . Robins . D. A. . Benson . C. T. . Development of a selective androgen receptor modulator for transdermal use in hypogonadal patients . Andrology . 2018 . 6 . 3 . 455–464 . 10.1111/andr.12479. 29527831 . 3858281 . free .
  40. Web site: MK 0773 . AdisInsight . Springer Nature Switzerland AG . 2024-01-14 . 2023-07-09 . https://web.archive.org/web/20230709065556/https://adisinsight.springer.com/drugs/800024550 . live .
  41. Papanicolaou DA, Ather SN, Zhu H, Zhou Y, Lutkiewicz J, Scott BB, Chandler J . A phase IIA randomized, placebo-controlled clinical trial to study the efficacy and safety of the selective androgen receptor modulator (SARM), MK-0773 in female participants with sarcopenia . J Nutr Health Aging . 17 . 6 . 533–43 . 2013 . 23732550 . 10.1007/s12603-013-0335-x . 42439768 . free .
  42. Web site: MK0773 Intervention/Treatment Search Results . ClinicalTrials.gov . U.S. National Library of Medicine . 2024-02-08 . 2024-02-08 . https://web.archive.org/web/20240208092050/https://clinicaltrials.gov/search?intr=MK0773&viewType=Table . live .
  43. Web site: OPK 88004 . AdisInsight . Springer Nature Switzerland AG . 2024-01-14 . 2024-01-03 . https://web.archive.org/web/20240103033149/https://adisinsight.springer.com/drugs/800033580 . live .
  44. Pencina . Karol M . Burnett . Arthur L . Storer . Thomas W . Guo . Wen . Li . Zhuoying . Kibel . Adam S . Huang . Grace . Blouin . Michelle . Berry . Donna L . Basaria . Shehzad . Bhasin . Shalender . A Selective Androgen Receptor Modulator (OPK-88004) in Prostate Cancer Survivors: A Randomized Trial . The Journal of Clinical Endocrinology & Metabolism . 2021 . 106 . 8 . 2171–2186 . 10.1210/clinem/dgab361 . 34019661 . 8277210 .
  45. Web site: OPK-88004 Intervention/Treatment Search Results . ClinicalTrials.gov . U.S. National Library of Medicine . 2024-02-11 . 2024-03-08 . https://web.archive.org/web/20240308031541/https://clinicaltrials.gov/search?intr=OPK-88004&viewType=Table . live .
  46. Web site: PF 626414 . AdisInsight . Springer Nature Switzerland AG . 2024-01-14 . 2024-01-14 . https://web.archive.org/web/20240114011910/https://adisinsight.springer.com/drugs/800040072 . live .
  47. Web site: PF-06260414 Intervention/Treatment Search Results . ClinicalTrials.gov . U.S. National Library of Medicine .
  48. Web site: PS 178990 . AdisInsight . Springer Nature Switzerland AG . 2024-01-14 . 2024-01-14 . https://web.archive.org/web/20240114011911/https://adisinsight.springer.com/drugs/800027228 . live .
  49. Web site: PS-178990 . Synapse . PatSnap . 2024-01-14 . 2024-01-14 . https://web.archive.org/web/20240114014848/https://synapse.patsnap.com/drug/78c027bec8a44220832e3922dbd38dfb . live .
  50. Web site: Vosilasarm - Ellipses Pharma . AdisInsight . Springer Nature Switzerland AG . 2024-01-12 . 2024-01-03 . https://web.archive.org/web/20240103033122/https://adisinsight.springer.com/drugs/800028398 . live .
  51. Web site: RAD140 Intervention/Treatment Search Results . ClinicalTrials.gov . U.S. National Library of Medicine .
  52. Lee . Su Jin . Gharbi . Amal . Shin . Joo Eun . Jung . In Duk . Park . Yeong Min . Myostatin inhibitor YK11 as a preventative health supplement for bacterial sepsis . Biochemical and Biophysical Research Communications . 2021 . 543 . 1–7 . 10.1016/j.bbrc.2021.01.030 . 33588136 . 231938058 . 0006-291X. free .
  53. Leciejewska N, Jędrejko K, Gómez-Renaud VM, Manríquez-Núñez J, Muszyńska B, Pokrywka A . Selective androgen receptor modulator use and related adverse events including drug-induced liver injury: Analysis of suspected cases . European Journal of Clinical Pharmacology . 80 . 2 . 185–202 . February 2024 . 38059982 . 10847181 . 10.1007/s00228-023-03592-3 .
  54. Book: Zajac . Jeffrey D. . Seeman . Ego . Russell . Nicholas . Ramchand . Sabashini K. . Bretherton . Ingrid . Grossmann . Mathis . Davey . Rachel A. . Encyclopedia of Bone Biology . 2020 . Academic Press . 978-0-12-814082-6 . 545 . Testosterone. .
  55. Book: Sigalos . John T. . Walker . Dyvon T. . Lipschultz . Larry I. . Men's Reproductive and Sexual Health Throughout the Lifespan: An Integrated Approach to Fertility, Sexual Function, and Vitality. Selective Androgen Receptor Modulators in the Treatment of Hypogonadism and Men's Health . 2023 . Cambridge University Press . 10.1017/9781009197533.034 . 978-1-009-19755-7 . 266 . en.
  56. Dai . Charles . Ellisen . Leif W . Revisiting Androgen Receptor Signaling in Breast Cancer . The Oncologist . 2023 . 28 . 5 . 383–391 . 10.1093/oncolo/oyad049 . 36972361 . 10166165 . 2023-09-10 . 2023-10-12 . https://web.archive.org/web/20231012045405/https://academic.oup.com/oncolo/article/28/5/383/7087214 . live .
  57. Palmieri . Carlo . Linden . Hannah M. . Birrell . Stephen . Lim . Elgene . Schwartzberg . Lee S. . Rugo . Hope S. . Cobb . Patrick Wayne . Jain . Kirti . Vogel . Charles L. . O'Shaughnessy . Joyce . Johnston . Stephen R. D. . Getzenberg . Robert H. . Barnette . K. Gary . Steiner . Mitchell S. . Brufsky . Adam . Overmoyer . Beth . Efficacy of enobosarm, a selective androgen receptor (AR) targeting agent, correlates with the degree of AR positivity in advanced AR+/estrogen receptor (ER)+ breast cancer in an international phase 2 clinical study. . Journal of Clinical Oncology . 2021 . 39 . 15_suppl . 1020 . 10.1200/JCO.2021.39.15_suppl.1020 . 236407030 . en . 0732-183X . 2023-09-10 . 2023-10-12 . https://web.archive.org/web/20231012045409/https://ascopubs.org/doi/abs/10.1200/JCO.2021.39.15_suppl.1020 . live .
  58. Web site: FDA Grants Fast Track Designation to Enobosarm in AR+, ER+, HER2- Metastatic Breast Cancer . Cancer Network . 27 August 2023 . en . 10 January 2022 . 27 August 2023 . https://web.archive.org/web/20230827004207/https://www.cancernetwork.com/view/fda-grants-fast-track-designation-to-enobosarm-in-ar-er-her2--metastatic-breast-cancer . live .
  59. Lim . Elgene . Hamilton . Erika . Palmieri . Carlo . Arkenau . Hendrik-Tobias . Brook . Sue . Fisher . Geoff . Mazur . Andrew . Abstract OT1-02-02: A phase 1/2 study to evaluate the safety and efficacy of EP0062, an oral Selective Androgen Receptor Modulator (SARM), for the treatment of AR+/HER2-/ER+ advanced breast cancer . Cancer Research . 1 March 2023 . 83 . 5_Supplement . OT1–02–02-OT1-02-02 . 10.1158/1538-7445.SABCS22-OT1-02-02. 257320030 .
  60. Fonseca . Guilherme Wesley Peixoto Da . Dworatzek . Elke . Ebner . Nicole . Von Haehling . Stephan . Selective androgen receptor modulators (SARMs) as pharmacological treatment for muscle wasting in ongoing clinical trials . Expert Opinion on Investigational Drugs . 2020 . 29 . 8 . 881–891 . 10.1080/13543784.2020.1777275. 32476495 . 219174372 .
  61. Christiansen . Andrew R. . Lipshultz . Larry I. . Hotaling . James M. . Pastuszak . Alexander W. . Selective androgen receptor modulators: the future of androgen therapy? . Translational Andrology and Urology . March 2020 . 9 . Suppl 2 . S135–S148 . 10.21037/tau.2019.11.02 . 32257854 . 7108998 . 2223-4683 . free .
  62. Zhang X, Sui Z . Deciphering the selective androgen receptor modulators paradigm . Expert Opin Drug Discov . 8 . 2 . 191–218 . February 2013 . 23231475 . 10.1517/17460441.2013.741582 . 2584722 .
  63. Bhasin. Shalender . Selective Androgen Receptor Modulators as Function Promoting Therapies . The Journal of Frailty & Aging . 2015 . 4 . 3 . 121–122 . 10.14283/jfa.2015.65 . 27030938 . 6039107 . 2260-1341.
  64. Sobolevsky . Tim . Ahrens . Brian . High-throughput liquid chromatography tandem mass spectrometry assay as initial testing procedure for analysis of total urinary fraction . Drug Testing and Analysis . 2021 . 13 . 2 . 283–298 . 10.1002/dta.2917 . 32852861 . 221347916 . en . 1942-7603 . 2023-09-01 . 2023-09-01 . https://web.archive.org/web/20230901042950/https://analyticalsciencejournals.onlinelibrary.wiley.com/doi/abs/10.1002/dta.2917 . live .
  65. Turnock . Dr Luke . Gibbs . Dr Nick . Click, click, buy: The market for novel synthetic peptide hormones on mainstream e-commerce platforms in the UK . Performance Enhancement & Health . 2023 . 11 . 2 . 100251 . 10.1016/j.peh.2023.100251 . 257706930 . 2211-2669. free .
  66. Web site: Oberheiden . Nick . The FDA Continues to Crack Down on SARM Manufacturing and Distribution . Federal Lawyer . 13 October 2023 . 26 June 2023 . 4 November 2023 . https://web.archive.org/web/20231104170150/https://federal-lawyer.com/the-fda-continues-to-crack-down-on-sarm-manufacturing-and-distribution/ . live .
  67. News: Jacobson . Hogan Lovells-Mandi . Zhang . Angell . Forrai . Zachary . Failure to remove unlawful advertising attracts $12 million penalty . 13 October 2023 . Lexology . 3 August 2021 . en . 4 November 2023 . https://web.archive.org/web/20231104170149/https://www.lexology.com/library/detail.aspx?g=311cfe98-f39e-415b-8a56-0fba4f091c5f . live .
  68. Hahamyan . Henrik A. . Vasireddi . Nikhil . Voos . James E. . Calcei . Jacob G. . Social media's impact on widespread SARMs abuse . The Physician and Sportsmedicine . 2023 . 51 . 4 . 291–293 . 10.1080/00913847.2022.2078679 . 35574698 . 248812455 . en . 0091-3847. free .
  69. Handschin . Christoph . Caloric restriction and exercise mimetics: Ready for prime time? . Pharmacological Research . 2016 . 103 . 158–166 . 10.1016/j.phrs.2015.11.009. 26658171 . 4970791 .
  70. Xie . Youquan . Tian . Yucheng . Zhang . Yuming . Zhang . Zhisheng . Chen . Rui . Li . Mian . Tang . Jiawei . Bian . Jinlei . Li . Zhiyu . Xu . Xi . Overview of the development of selective androgen receptor modulators (SARMs) as pharmacological treatment for osteoporosis (1998–2021) . European Journal of Medicinal Chemistry . 15 February 2022 . 230 . 114119 . 10.1016/j.ejmech.2022.114119 . 35063736 . 245941791 . 0223-5234.
  71. Efimenko . Iakov V. . Valancy . David . Dubin . Justin M. . Ramasamy . Ranjith . Adverse effects and potential benefits among selective androgen receptor modulators users: a cross-sectional survey . International Journal of Impotence Research . 2022 . 34 . 8 . 757–761 . 10.1038/s41443-021-00465-0 . 34471228 . 237378326 . en . 1476-5489.
  72. Kintz . Pascal . Ameline . Alice . Gheddar . Laurie . Raul . Jean-Sébastien . LGD-4033, S-4 and MK-2866 – Testing for SARMs in hair: About 2 doping cases . Toxicologie Analytique et Clinique . 2019 . 31 . 1 . 56–63 . 10.1016/j.toxac.2018.12.001 . 2019ToxAC..31...56K . 2352-0078 . 2023-08-30 . 2023-08-30 . https://web.archive.org/web/20230830031059/https://www.sciencedirect.com/science/article/abs/pii/S2352007818303275 . live .
  73. Web site: Selektive Androgenrezeptor-Modulatoren (SARMs) . . 1 September 2023 . de . 1 September 2023 . https://web.archive.org/web/20230901042955/https://www.dshs-koeln.de/institut-fuer-biochemie/doping-substanzen/doping-lexikon/s/selektive-androgenrezeptor-modulatoren-sarms/ . live .
  74. Kintz . Pascal . The forensic response after an adverse analytical finding (doping) involving a selective androgen receptor modulator (SARM) in human athlete . Journal of Pharmaceutical and Biomedical Analysis . 5 January 2022 . 207 . 114433 . 10.1016/j.jpba.2021.114433 . 34715583 . 240229684 . 1873-264X. free .
  75. Hahamyan . Henrik . Gould . Heath . Gregory . Andrew . Dodson . Christopher . Gausden . Elizabeth . Voos . James . Calcei . Jacob . Vasireddi . Nikhil . Poster 390: Systematic Review of SARMs Abuse in Athletes . Orthopaedic Journal of Sports Medicine . 2023 . 11 . 7_suppl3 . 2325967123S00352 . 10.1177/2325967123S00352 . 260375399 . en . 2325-9671. free . 10392554 .
  76. Warrier . Alec A. . Azua . Eric N. . Kasson . Luke B. . Allahabadi . Sachin . Khan . Zeeshan A. . Mameri . Enzo S. . Swindell . Hasani W. . Tokish . John M. . Chahla . Jorge . Performance-Enhancing Drugs in Healthy Athletes: An Umbrella Review of Systematic Reviews and Meta-analyses . Sports Health: A Multidisciplinary Approach . 2023 . 10.1177/19417381231197389 . 37688400 . 261620672 . en . 1941-7381 . 2023-10-12 . 2023-11-04 . https://web.archive.org/web/20231104170149/https://journals.sagepub.com/doi/abs/10.1177/19417381231197389 . live .
  77. Tauchen J, Jurášek M, Huml L, Rimpelová S . Medicinal Use of Testosterone and Related Steroids Revisited . Molecules . 26 . 4 . February 2021 . 1032 . 33672087 . 7919692 . 10.3390/molecules26041032 . free . SARMs are a novel group of compounds developed to selectively augment anabolic effects in muscles and bones, while avoiding undesirable androgenic effects in skin, larynx, and reproductive organs. The majority of these compounds lack the structural functionalities of the original anabolic steroids and are sometimes termed nonsteroidal androgens. It was hoped that these agents could be used in cases where conventional anabolic steroids produced undesirable side-effects, such as virilization in women and prostate hyperplasia in men [67]. Despite the enormous effort that has been expended in the development of selective anabolic agents, the androgenic effect is very hard to remove completely and many of the currently developed SARMs still do have some androgenic activity..
  78. Brown TR . Nonsteroidal selective androgen receptors modulators (SARMs): designer androgens with flexible structures provide clinical promise . Endocrinology . 145 . 12 . 5417–9 . December 2004 . 15545403 . 10.1210/en.2004-1207 .
  79. Xie Y, Tian Y, Zhang Y, Zhang Z, Chen R, Li M, Tang J, Bian J, Li Z, Xu X . Overview of the development of selective androgen receptor modulators (SARMs) as pharmacological treatment for osteoporosis (1998-2021) . Eur J Med Chem . 230 . 114119 . February 2022 . 35063736 . 10.1016/j.ejmech.2022.114119 . 245941791 .
  80. Dalton JT, Mukherjee A, Zhu Z, Kirkovsky L, Miller DD . Discovery of nonsteroidal androgens . Biochem Biophys Res Commun . 244 . 1 . 1–4 . March 1998 . 9514878 . 10.1006/bbrc.1998.8209 .
  81. Negro-Vilar A . Selective androgen receptor modulators (SARMs): a novel approach to androgen therapy for the new millennium . The Journal of Clinical Endocrinology and Metabolism . 84 . 10 . 3459–3462 . October 1999 . 10522980 . 10.1210/jcem.84.10.6122 . We have chosen the term selective androgen receptor modulators (SARMs) after the terminology currently used for similar molecules targeting the estrogen receptor. ... Desired profile of activity of new SARMs: male applications: Selected indications may include glucocorticoid-induced osteoporosis, androgen replacement in elderly men, HIV-wasting, cancer cachexia, certain anemias, muscular dystrophies, and male contraception. .
  82. Handelsman DJ . History of androgens and androgen action . Best Practice & Research. Clinical Endocrinology & Metabolism . 36 . 4 . 101629 . July 2022 . 35277356 . 10.1016/j.beem.2022.101629 . The next invention was that of the first non-steroidal androgen by Dalton et al. [111] in 1998, six decades after the first non-steroidal estrogen [112]. This creates a new class of non-steroidal synthetic androgen, often termed Specific Androgen Receptor Modulators (SARM), a misleading marketing term rather than an accurate pharmacological description [113,114], usurping a speculative but unsound analogy with Specific Estrogen Receptor Modulators (SERM). [...] none of the non-steroidal androgens under development [116,117] are marketed by 2021. Yet hope springs eternal for this new attempt to separate anabolic from androgenic properties of androgens to facilitate marketing for muscle wasting and other selective effects of testosterone. .
  83. Handelsman DJ . Commentary: androgens and "anabolic steroids": the one-headed janus . Endocrinology . 152 . 5 . 1752–4 . May 2011 . 21511988 . 10.1210/en.2010-1501 . Although development of the first nonsteroidal androgens (17, 18) as candidate selective AR modulators (19) raises hope of resurrecting this defunct term (20), prereceptor activation mechanisms cannot apply to nonsteroidal androgens, and the singular AR lacks a dual drive mechanism of the other paired sex steroid receptors. Consequently, it is not surprising that available knowledge (21) provides only slender hope that this failed, and probably false, dichotomy will now succeed through a renewed search guided by the same in vivo bioassay..
  84. Handelsman DJ . Androgen Misuse and Abuse . Endocr Rev . 42 . 4 . 457–501 . July 2021 . 33484556 . 10.1210/endrev/bnab001 . However, a third major quest, for the development of a nonvirilizing androgen (“anabolic steroid”) suitable for use in women and children, based on dissociating the virilizing from the anabolic effects of androgens failed comprehensively (36). This failure is now understood as being due to the discovery of a singular androgen receptor (AR) together with the misinterpretation of nonspecific whole animal androgen bioassays employed to distinguish between anabolic and virilizing effects (37). The term “androgen” is used herein for both endogenous and synthetic androgens including references to chemicals named elsewhere as “anabolic steroids,” “anabolic-androgenic steroids,” or “specific AR modulators” (SARM), which continue to make an obsolete and oxymoronic distinction between virilizing and anabolic effects of androgens where there is no difference (36)..
  85. Book: Handelsman, David J. . Testosterone . Androgen therapy in non-gonadal disease . Cambridge University Press . 2012-07-26 . 978-1-139-00335-3 . 10.1017/cbo9781139003353.018 . 372–407 . The development of nonsteroidal androgens, marketed as “selective androgen receptor modulators” (SARMs), offers new possibilities for adjuvant pharmacological androgen therapy. In contrast to the full spectrum of androgen effects of testosterone, such SARMs would be pure androgens not subject to tissue-specific activation by aromatization to a corresponding estrogen or to amplification of androgenic potency by 5α-reduction. In this context the endogenous pure androgens nandrolone and DHT can be considered prototype SARMs. SARMs are not the modern embodiment of so-called “anabolic steroids,” an outdated term referring to hypothetical but nonexistent non-virilizing androgens targeted exclusively to muscle, a failed concept lacking biological proof of principle (Handelsman 2011)..

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