SARMs in 2026: mechanism, comparison to peptides and steroids, and the legal mess.

The 52 percent problem

Start with the number. In 2017, a team at the Sports Medicine Research and Testing Laboratory in Salt Lake City, with Shalender Bhasin from Harvard, bought 44 products sold via the internet as selective androgen receptor modulators. They ran the full analytical chemistry workup — HPLC, mass spec, the whole stack. The headline finding, published in JAMA in November 2017: only 23 of the 44 products (52 percent) actually contained a SARM. Another 39 percent contained an unapproved drug that was not on the label. Nine percent contained no active substance at all. Twenty-five percent contained compounds the buyer was never told about — including aromatase inhibitors and clenbuterol.¹

Hold that finding in the foreground for the rest of this piece. Every mechanism paragraph, every comparison to steroids or peptides, every clinical-trial reference assumes the bottle in the user’s hand contains the molecule the user thinks it contains. The Van Wagoner data says, plainly, that on average in 2017 it did not.

What SARMs actually are

Selective androgen receptor modulators are a class of small non-steroidal compounds designed to bind the androgen receptor (AR) and produce anabolic effects in muscle and bone while producing far less activity in prostate, skin, and the broader virilizing axis. The original aryl-propionamide scaffolds were described by James T. Dalton and colleagues at the University of Tennessee in 1998. Ligand Pharmaceuticals developed a quinolone-core SARM family in parallel.⁶ These were genuine pharmaceutical-industry development programs targeted at sarcopenia, cancer cachexia, hypogonadism, osteoporosis, and breast-cancer endocrine therapy — not bodybuilding.

The commercial trail since then is a study in attrition. GTx Inc., which carried enobosarm (ostarine, GTx-024) through Phase 3, dissolved its independent corporate existence in 2018 after the POWER cachexia program produced mixed efficacy data and merged with Oncternal Therapeutics in 2019. Radius Health divested RAD-140 (testolone) to the UK’s Ellipses Pharma in October 2020 to refocus on its osteoporosis franchise.¹³ Viking Therapeutics still holds VK5211 (LGD-4033, licensed from Ligand in 2014) and reported a positive Phase 2 readout in hip-fracture muscle recovery in 2017, then pivoted attention to its GLP-1/GIP obesity program (VK2735) for the back half of the decade.¹⁴ Veru, which acquired enobosarm rights from GTx’s remnants, ran a Phase 3 ARTEST trial in androgen-receptor-positive metastatic breast cancer; it announced enrolment discontinuation in 2023 and shifted to its earlier-line ENABLAR-2 study.¹⁵

As of May 2026, zero SARMs are approved by the FDA, Health Canada, the EMA, the MHRA or the TGA for any human indication. That is the unambiguous starting point for every other conversation about this class.

Mechanism: the signal SARMs pull

Testosterone and dihydrotestosterone (DHT) work by binding the androgen receptor, displacing heat-shock-protein chaperones, translocating into the nucleus, and recruiting a tissue-specific cast of co-activator and co-repressor proteins to androgen- responsive gene promoters. The downstream signal — muscle protein synthesis, erythropoiesis, libido, prostate growth, sebaceous activity, virilization — depends on which co-regulators a given tissue expresses.

SARMs are designed to exploit that tissue-specificity. They bind the same AR but, because of their non-steroidal scaffold, induce a slightly different receptor conformation. That altered shape recruits a different mix of co-regulators in muscle and bone versus prostate, skin, and seminal vesicle. In rodent assays, that translates to anabolic activity (myotrophic, osteotrophic) with substantially reduced activity in androgen-dependent accessory tissues — the classic Hershberger split between the levator ani and the ventral prostate.⁴ That is the signal SARMs were built to pull: the muscle and bone arm of the androgen response without the full virilizing and prostatic arm.

How clean that selectivity is in humans, at the doses recreational users run, is a separate question. The data say it is partial, not total. LGD-4033 at 1.0 mg daily for 21 days in healthy young men suppressed total testosterone roughly 55 percent and free testosterone roughly 45 percent from baseline, with proportional drops in luteinizing hormone (LH) and follicle-stimulating hormone (FSH) — signature hypothalamic-pituitary-gonadal (HPG) suppression.² That happens because the pituitary doesn’t care which AR agonist is in circulation; an active androgen signal feeds back to shut down gonadotropin release. Selectivity in the muscle does not buy selectivity in the brain’s view of total androgen tone.

“The pituitary doesn’t care which AR agonist is in circulation. The HPG shut-off is a feature of the signal, not a side effect.”

SARMs vs anabolic steroids

The community pitch for SARMs has always been “the anabolic effect of steroids, without the side effects.” That deserves to be taken apart honestly.

Three real differences exist. SARMs don’t aromatize — they aren’t substrates for aromatase, so they don’t convert into estradiol the way exogenous testosterone does. SARMs aren’t substrates for 5α-reductase in any meaningful way, so they don’t generate DHT-related signal in scalp or prostate at the receptor level. SARMs are oral and don’t require 17α-alkylation for oral bioavailability the way classic oral steroids do, which sidesteps the most aggressive hepatotoxicity profile (think Anadrol, Dianabol, Winstrol) baked into that chemistry.

Those are genuine pharmacological wins on paper. The problem is what they don’t buy you.

SARMs still suppress the HPG axis. The Basaria LGD-4033 Phase 1 result is the clean demonstration.² SARMs still drop HDL — the Basaria paper showed roughly a 20 percent HDL decline at 1 mg LGD-4033 within three weeks, the same direction-of-effect oral steroids produce, just less violent. SARMs still elevate ALT and AST in a meaningful minority of users. The published RAD-140 cases describe ALT and AST elevations into the thousands of units per litre, severe cholestatic hepatitis, weeks of jaundice, and in one published case progression toward liver-transplant evaluation before recovery.⁷⁸ The NIH’s LiverTox SARM monograph — the same evidence-curation body that grades prescription drug hepatotoxicity — categorizes SARMs as a recognized cause of drug-induced liver injury, with case-series-quality evidence.⁹

The honest version of the comparison: SARMs cut some of the cosmetic and prostate-axis liabilities of testosterone esters. They do not eliminate cardiovascular, hepatic, or gonadal-axis liability. The “safer steroid” framing buys a partial discount, not an exemption. For readers weighing the HPG-suppression question against the legitimate clinical alternative, the enclomiphene-and-hCG path that preserves endogenous testosterone is the cleaner reference point than a SARM cycle.

SARMs vs peptides

SARMs and peptides get bundled together in community conversation because they share a regulatory grey zone and a delivery culture. Pharmacologically, they have almost nothing in common.

Peptides are short chains of amino acids that pull defined signals through receptors the body already uses for its own signaling traffic — growth hormone (CJC-1295 with Ipamorelin is the canonical GH-releasing pair, plus Tesamorelin and Hexarelin), ghrelin (GHRP-2, GHRP-6, MK-677 via the GHS-R), melanocortin (PT-141, Melanotan II), glucagon-axis (GLP-1 analogs, glucagon analogs — the GLP-1 with AOD-9604 stack is the lean-mass-preserving variant), insulin-mimetic, healing (BPC-157, TB-500). Different peptides pull different signals, and most of those signals come with a built-in feedback loop: the pituitary doses growth hormone in pulses, then shuts itself off; a meal closes the ghrelin loop; a sated state damps further GLP-1 release. The peptides ride those native rhythms.

SARMs do something fundamentally different. There is one signal — the androgen receptor — and SARMs bind it directly. There is no analogue of pituitary pulsatility for the AR axis. There is no “sated” feedback that eases SARM occupancy of the receptor. The compound binds, the gene-expression program runs, the HPG axis shuts off natural testosterone production, and the only feedback in the system is the steady-state pharmacokinetics of the molecule itself.

This matters because the editorial position this site is built on — the foundational thesis that runs through The Manual — is that preservation tools should ride the body’s own feedback systems, not bypass them. Growth-hormone-releasing peptides ask the pituitary to do its job; they don’t flood the receptor. SARMs and anabolic steroids both flood the AR receptor and silence the body’s natural production. That distinction — preservation of feedback versus bypass of feedback — is the core difference between the two classes, and it’s the reason the comparison is category-different rather than just dose-different.

What the clinical-trial record actually shows

Across roughly twenty-five years of development, the SARM clinical record breaks into three buckets.

Enobosarm (ostarine, GTx-024, MK-2866) has the deepest record. The Phase 2 cancer-cachexia trial published by Adrian Dobs and colleagues in Lancet Oncology in 2013 randomized 159 patients with non-small-cell lung cancer, colorectal cancer, breast cancer, ovarian cancer, or chondrosarcoma and showed dose-dependent increases in lean body mass at 1 mg and 3 mg daily over 16 weeks.³ That signal carried into the Phase 3 POWER trials in NSCLC cachexia, which produced mixed efficacy results on the co-primary endpoints (lean body mass improved consistently; physical function as measured by stair-climb did not), and enobosarm did not secure regulatory approval. Veru subsequently pursued enobosarm in androgen-receptor-positive oestrogen-receptor-positive HER2-negative metastatic breast cancer; the Phase 3 ARTEST monotherapy study was discontinued in 2023 to focus development on the earlier-line ENABLAR-2 combination with abemaciclib.¹⁵

LGD-4033 (ligandrol, VK5211) has Basaria’s 2013 healthy-volunteer Phase 1 demonstrating safety, dose-proportional lean-mass gain, and the HPG/lipid signature.² Viking Therapeutics’ Phase 2 in 108 hip-fracture patients produced statistically significant, dose-dependent lean body mass gains of 4.8 to 9.1 percent over twelve weeks; that program has not moved into Phase 3 in the years since, with Viking’s capital and attention concentrated on its metabolic franchise.¹⁴

RAD-140 (testolone), originally a Radius Health asset, had Phase 1a data in heavily pre-treated postmenopausal women with ER+/HER2- locally advanced or metastatic breast cancer before Radius divested the program to Ellipses Pharma in October 2020 to refocus on its osteoporosis franchise around abaloparatide.¹³ Ellipses has continued early-phase oncology work; no Phase 3 readout exists.

The underlying reason no SARM has crossed the regulatory finish line, after a quarter century of development capital, is the consistent appearance of three signals in larger trials: liver enzyme elevations, HDL reductions, and HPG suppression that translates to slow recovery of endogenous testosterone after cessation. Dalton’s own 2017 retrospective in British Journal of Clinical Pharmacology — written by the chemist who originally described the class — was titled, with deliberate understatement, “The long and winding road for selective androgen receptor modulators.”⁵

The legal map — US, Canada, UK, Australia, sport

SARMs occupy slightly different legal positions in every major jurisdiction, but the operative reality is the same: no SARM is approved as a medicine anywhere, and all SARMs are prohibited in regulated sport.

United States. SARMs are not Schedule III federally as of May 2026 — periodic SARMs Control Act legislation has been introduced in Congress since 2018 but has not become law. The FDA treats SARMs as unapproved new drugs and has issued repeated warning letters across the 2017 to 2025 window, including December 2025 letters to Atomix LLC and Prime Sports Nutrition for offering LGD-4033, RAD-140, MK-677, and S-23 in supplement format. The FDA’s consumer-facing guidance — under the title “FDA Warns of Use of Selective Androgen Receptor Modulators (SARMs) Among Teens, Young Adults” — lists heart attack, stroke, psychosis, sexual dysfunction, liver injury and failure, infertility, and testicular shrinkage as documented adverse events.¹⁰ The DOJ has pursued product-mislabeling cases that lean on misbranding statutes rather than controlled-substance law.

Canada. Health Canada is direct: SARMs are not authorized in Canada for any use and have not been reviewed by Health Canada for safety, effectiveness, or quality. The Canada Border Services Agency seizes SARM shipments deemed to be for human consumption at the border. Selling SARMs domestically is illegal. Health Canada explicitly lists liver damage, cardiovascular events, lipid disturbance, fluid retention, infertility, decreased libido, sexual dysfunction, and gynaecomastia among the adverse outcomes documented in the consumer alerts published on canada.ca.¹¹ Enforcement actions during 2023–2025 have included multi-store seizures of SARMs, injectable peptides, and anabolic steroids in BC, Alberta, and Ontario, with public-advisory follow-ups.

United Kingdom. SARMs are not licensed medicines and cannot legally be marketed as supplements. The MHRA has issued enforcement against vendors marketing SARMs as nutritional products and the ASA has upheld complaints against advertising.

Australia. SARMs are Schedule 4 (prescription-only) under the Therapeutic Goods Act, which makes possession without prescription and importation without authorization an offence. TGA enforcement against vendors and importers has been more aggressive than in most Western jurisdictions.

Sport. SARMs were added to the WADA Prohibited List in 2008 and now sit in section S1.2 (“Other Anabolic Agents”), with andarine, enobosarm (ostarine), LGD-4033, RAD-140, S-23, and YK-11 named explicitly and the catch-all “other substances with a similar chemical structure or similar biological effect” covering the rest. SARMs are prohibited at all times, in and out of competition, at every level of WADA-coded sport — from elite to recreational. The NCAA, NFL, MLB, UFC, and USADA enforcement schedules all mirror the WADA position.¹²

The 52 percent problem, in full

Return now to the Van Wagoner data and look at the full granularity. Of 44 retail SARM products tested:¹

• 23 (52 percent) contained the labeled SARM.
• 17 (39 percent) contained a different unapproved drug than the one on the label — including aromatase inhibitors and clenbuterol.
• 4 (9 percent) contained no active substance at all.
• 26 (59 percent) contained an amount of substance that differed from the label, in either direction.
• 11 (25 percent) contained the labeled compound but at a mass that didn’t match the dose declared.

Pause on the aromatase-inhibitor finding for a moment. Letrozole and anastrozole are prescription oncology drugs used to suppress estrogen synthesis in post-menopausal breast cancer. Putting them in an unlabeled supplement sold to a 22-year-old recreational user is the kind of unacknowledged exposure that can drive bone density loss, joint pain, lipid disturbance, and sexual dysfunction with no path back to the cause when the user describes “side effects from the SARM cycle.” Clenbuterol, a beta-2 agonist used in some countries for veterinary respiratory medicine, has its own cardiac and thermogenic profile that does not belong in a product sold as an androgen-receptor modulator.

The published RAD-140 liver-injury case reports tie back to this directly. Several authors note that absent third-party-verified content analysis, it is impossible to cleanly attribute the hepatotoxicity to RAD-140 itself versus an unlabeled co-contaminant.⁷⁸ The molecule mechanism makes hepatotoxicity plausible. The retail-supply chain makes attribution forensic-grade difficult. Both things are true simultaneously, and both complicate any clean read of the risk profile.

Safety signals from the case literature

Setting aside the labeling problem and assuming, for a moment, that a user is actually receiving the SARM they ordered, six signals recur across the case and small-trial literature.

HPG suppression. Total and free testosterone crash within weeks of starting most SARMs at recreational doses. LH and FSH suppress in parallel. Recovery after cessation is typically partial within four to eight weeks and full within twelve to sixteen, but a meaningful minority of users in case reports show prolonged suppression requiring clinical management with hCG or SERM-based recovery protocols.²⁴

HDL drop. Most SARMs produce a 15 to 30 percent HDL reduction within four weeks of starting, proportional to dose. Direction of effect mirrors oral anabolic steroids. Repeat lipid panels are the cheapest way to detect this; many community users simply don’t pull baseline labs and never see the change.²

ALT and AST elevation. A meaningful minority of users develop transaminase elevations — sometimes mild and resolving with cessation, sometimes severe and requiring hospitalization. RAD-140 has the worst published case-report record on this front, with ALT and AST values in the high thousands of units per litre documented in young users with no prior hepatic disease.⁷⁸

Cardiac case reports. Isolated published cases link SARM use to myocardial infarction in young users without traditional risk factors. The mechanism is plausible (HDL drop, lipid disturbance, possible direct vascular effects) but the case-report literature is small and selection-biased toward severe outcomes.

Hair shedding. RAD-140 has the most prominent case-report record for accelerated androgenic alopecia, which is somewhat ironic given the original tissue-selectivity pitch. Users with a genetic predisposition appear to accelerate hair loss within weeks.

Gynecomastia from estrogen rebound. Counter- intuitively, SARMs that don’t themselves aromatize can still drive gynecomastia — the HPG suppression flips the ratio between residual testosterone and circulating estradiol toward estrogen dominance, and aromatase activity in adipose tissue does the rest. Several published cases document gynecomastia that persisted past cessation and required surgical correction.

What “research chemical” actually means

Every bottle of SARMs sold legally in North America carries a label that reads, in some variant, “for research purposes only, not for human consumption.” That label is the legal fiction the entire retail SARM industry is built on.

It works the way it works because possessing a compound labeled as a research reagent is treated differently under FDCA and Food and Drugs Act jurisprudence than possessing the same compound marketed for human use. The FDA’s response, documented across years of warning letters and addressed explicitly in their consumer-facing guidance, is that intention-to-sell-for-human-use can be inferred from website copy, packaging context, customer-service behaviour, and adverse-event reports — and once inferred, the “research only” label provides no shelter. The December 2025 warning letters to Atomix LLC and Prime Sports Nutrition lean exactly on that inference.¹⁰ Health Canada applies similar reasoning under the Food and Drugs Act, with CBSA seizure as the enforcement edge.¹¹

For the user, the operative reality is simpler. The “research only” label means there is no regulatory oversight of the product’s identity, purity, dose accuracy, contamination profile, or storage conditions. The Van Wagoner finding is what that absence of oversight produces at population scale. Nothing about the “research only” framing changes the safety calculus — it changes only the jurisdictional question of who is legally on the hook for the harm.

Community claims, three honest reads

Three claims circulate most often in community use. Each deserves an honest answer.

“SARMs give you 70 percent of steroid gains with 10 percent of the side effects.” The first half is closer to true at supraphysiological recreational doses than at therapeutic-trial doses. Lean-mass gains in the 4 to 9 percent range over twelve weeks are documented in the VK5211 Phase 2 and similar studies. The second half is misleading. SARMs cut some side effects of testosterone esters (no aromatization, no DHT, no 17α-alkylation hepatotoxicity at recreational doses), but they retain HPG suppression, HDL drop, ALT/AST elevation potential, cardiac case reports, and hair shedding. Calling that 10 percent of steroid side effects is wishful arithmetic.

“SARMs don’t require post-cycle therapy.” The Basaria data say they do, at recreational dose. Total testosterone suppression of 50-plus percent within three weeks at 1 mg LGD-4033 in healthy young men is not “no PCT needed.” It’s exactly the suppression pattern that pushed steroid users to PCT in the first place.

“Liver toxicity is overblown.” The published case-report record on RAD-140 alone — multiple independent papers describing severe drug-induced liver injury in young, otherwise-healthy users at recreational doses — doesn’t support that read. NIH’s LiverTox classifying SARMs as a recognized DILI cause doesn’t support it either. The honest version is that most users won’t experience clinically significant hepatotoxicity, but a meaningful minority will, and absent baseline plus mid-cycle ALT/AST monitoring there is no way to tell which group you’re in until you’re already symptomatic.⁷⁸⁹

Where this leaves a thoughtful reader

I’m not telling anyone to take SARMs. That isn’t the job of this article and it isn’t the position of this publication. What I will do is name the supervision case cleanly, because the worst outcomes in the SARM literature consistently involve users who never pulled labs.

If a reader has decided to act on this class, with a clinician involved, the floor for screening is roughly this. A full baseline panel before starting: comprehensive metabolic panel including ALT, AST, GGT and bilirubin; full lipid panel including HDL; complete CBC; total and free testosterone, LH, FSH, SHBG, estradiol (sensitive assay), and prolactin; PSA if over 40. Mid-cycle repeat of liver enzymes and lipids at the four-to-six-week mark. A post-cycle endocrine panel at four and twelve weeks after cessation. Resting blood pressure weekly through any cycle. The bloodwork is the only way to catch the slow, asymptomatic damage before it presents as something requiring hospitalization. The lipid piece deserves its own attention — a standard LDL number is not enough on a class that drops HDL hard, and the ApoB case for measuring particle count instead of cholesterol mass is the test to add.

Three populations should not run SARMs at all. Under 25. The HPG axis is still consolidating; suppressing it during that window risks long-term recovery and bone-density consequences. Family history of hormone-sensitive cancer — particularly first-degree relatives with breast, prostate, ovarian, or endometrial cancer. The mechanism overlap with these tumour biologies is direct, and population-scale safety data for chronic SARM exposure in this group does not exist. Existing lipid or hepatic issues. Any baseline ALT or AST above the upper reference, any HDL already below 40 mg/dL in men or 50 mg/dL in women, any history of NAFLD, cholestatic disease, or familial dyslipidemia. SARMs push those numbers the wrong direction; starting from a deficit is starting from too far back.

Pregnancy and breastfeeding are absolute exclusions. No human safety, fetal exposure, or lactation transfer data exist for any SARM. Any athlete competing under any anti-doping authority — recreational included — is also excluded as a practical matter; the WADA position covers Masters weightlifting and CrossFit affiliates as much as it covers the Olympics.¹²

The deepest point of this article comes back to the comparison with peptides. Peptides preserve feedback. SARMs and anabolic steroids bypass it. That is the foundational distinction this site is built around, and it’s the reason the recovery- and longevity-leaning protocols on wellnessradar.ca lean peptide-first and treat SARMs as a separate, narrower conversation. Selectivity in muscle does not buy selectivity in the brain’s view of androgen tone, and the HPG shut-off that follows is the visible signature of a class that talks to the receptor instead of the rhythm.

References

1. Van Wagoner RM, Eichner A, Bhasin S, et al. Chemical Composition and Labeling of Substances Marketed as Selective Androgen Receptor Modulators and Sold via the Internet. JAMA. 2017;318(20):2004-2010. PubMed.
2. Basaria S, Collins L, Dillon EL, et al. The Safety, Pharmacokinetics, and Effects of LGD-4033, a Novel Nonsteroidal Oral, Selective Androgen Receptor Modulator, in Healthy Young Men. J Gerontol A Biol Sci Med Sci. 2013;68(1):87-95. PubMed.
3. Dobs AS, Boccia RV, Croot CC, et al. Effects of enobosarm on muscle wasting and physical function in patients with cancer: a double-blind, randomised controlled phase 2 trial. Lancet Oncol. 2013;14(4):335-345. PubMed.
4. Solomon ZJ, Mirabal JR, Mazur DJ, et al. Selective Androgen Receptor Modulators: Current Knowledge and Clinical Applications. Sex Med Rev. 2019;7(1):84-94. PubMed.
5. Dalton JT. The long and winding road for selective androgen receptor modulators. Br J Clin Pharmacol. 2017;83(10):2131-2133. PubMed.
6. Bhasin S, Jasuja R. Selective androgen receptor modulators as function promoting therapies. Curr Opin Clin Nutr Metab Care. 2009;12(3):232-240. PMC.
7. Flores JE, Chitturi S, Walker S. Drug-Induced Liver Injury by Selective Androgenic Receptor Modulators (RAD-140). Ochsner J. 2022;22(4):361-365. PubMed.
8. Bedi H, Hammond C, et al. Selective Androgen Receptor Modulators Leading to Liver Injury: A Case Report. 2024. PMC.
9. National Institute of Diabetes and Digestive and Kidney Diseases. Selective Androgen Receptor Modulators. LiverTox: Clinical and Research Information on Drug-Induced Liver Injury. NIH. NCBI Bookshelf.
10. U.S. Food & Drug Administration. FDA Warns of Use of Selective Androgen Receptor Modulators (SARMs) Among Teens, Young Adults. Consumer Update. FDA.gov.
11. Government of Canada. Using Bodybuilding Products. Health Canada. canada.ca.
12. U.S. Anti-Doping Agency. Selective Androgen Receptor Modulators (SARMs) — Prohibited Class: Anabolic Agents. USADA. USADA.org.
13. Radius Health. Radius Health Divests RAD-140 Program to Ellipses Pharma. Press release. October 1, 2020. GlobeNewswire.
14. Viking Therapeutics. Positive Top-Line Results from Phase 2 Study of VK5211 in Patients Recovering from Hip Fracture. Press release. 2017. PR Newswire.
15. Veru Inc. Veru Reports Clinical Data from the Discontinued ARTEST Study of Enobosarm, Novel Selective Androgen Receptor Targeting Agonist, in AR+ ER+ HER2- Metastatic Breast Cancer. Investor relations. ir.verupharma.com.