More selective.
More muscle.
But separate from what?

LGD-4033 and enobosarm are nonsteroidal androgen-receptor modulators. Nonsteroidal describes their chemistry, not an absence of hormonal action. The receptor is a protein whose activity can influence gene regulation; changing the ligand can change its interactions with cellular machinery. Structural experiments show how nonsteroidal ligands can be accommodated by the receptor. A binding structure does not itself establish a safe therapeutic window in humans.^[1][2][4]

In preclinical work, S-22 and DHT produced different signaling and receptor-cofactor responses. Rat levator ani and prostate findings helped illustrate tissue differentiation. Cell and Xenopus experiments added mechanistic detail. These are models of how selectivity might arise, not evidence that a human quadriceps will grow by a specified amount while every other tissue remains untouched.^[3]

Receptor selectivity and tissue selectivity also answer different questions. Preferentially engaging one receptor is not the same as affecting only one organ. A receptor can be shared across tissues, while each tissue interprets its activation differently. Conversely, a favorable muscle-to-prostate result cannot certify the liver, cardiovascular system or reproductive axis. Each is a separate part of the benefit-risk assessment.

Exposure belongs in this explanation. Selectivity observed under one experimental condition cannot be assumed to survive arbitrary changes in concentration, duration or combinations. That is a limit on extrapolation, not a claim that a particular threshold has been established. The human studies must supply the relevant boundary.

A short early-phase study can show that a compound reaches measurable exposure and changes a biological endpoint. It cannot answer all the questions of a long training intervention. Nor does a study in older adults automatically estimate the response of younger, experienced lifters. Age, baseline function and the opportunity for improvement affect what a result means.

Comparing the headline kilogram numbers would ignore those differences. It would also mix different analysis populations and treatment periods. Randomization protects the comparison within each trial. It does not extend across two papers simply because both contain a placebo group.

There is another practical distinction: these experiments studied specified investigational drugs under controlled conditions. The evidence belongs first to that product, population and protocol. A label sold elsewhere with a matching abbreviation does not inherit the same identity or exposure certainty.

DXA lean mass is not a direct count of new muscle fibers or contractile protein. It includes nonfat soft tissue and is influenced by tissue water. That does not justify dismissing every gain as water. It means a body-composition result is more informative when paired with muscle imaging, strength, function and follow-up after treatment.

The early enobosarm result illustrates why analysis labels matter. Its absolute stair-power table used a different comparison scale and reported P=.049; the percentage-change figure used P=.013. Those are not interchangeable annotations for the same numerical effect. Here the figure above explicitly identifies the percentage analysis.^[2]

A nonsignificant functional outcome also needs careful wording. It does not prove an effect of exactly zero. It says this experiment did not demonstrate the claimed difference with its design and precision. Likewise, a statistically significant lean-mass result does not fill the missing functional result. Both observations can be true.

For hypertrophy, a stronger test would combine a relevant training population, standardized resistance training, adequate duration and a prespecified direct muscle-size endpoint. Strength would be measured separately, with withdrawals and adverse events retained in the interpretation. The existing findings make that experiment interesting; they do not make it unnecessary.

Hormone results need their own interpretation. Total testosterone and free testosterone are related but different measurements; changing the binding protein SHBG can change their relationship. A total-testosterone decline should not be converted automatically into a precise estimate of symptoms, fertility or recovery time. Equally, one reassuring free-testosterone result does not make an exposure hormonally inert.

The distinction between an observed recovery and a guarantee is especially important. Follow-up in a controlled trial describes those participants after that exposure. It does not establish recovery for every longer course, larger exposure, combination or unidentified product. There is no evidentiary shortcut from a short study to a universal post-use outcome.

Lipid and liver measurements are not interchangeable with clinical events. A change in HDL does not let us calculate an individual's heart-attack probability from these trials. An ALT rise is not synonymous with liver failure. But both are relevant signals when assessing the claim that the mechanism has been confined to muscle.

The current FDA communication identifies SARMs products as unapproved drugs, not dietary supplements. It describes serious liver injuries requiring hospitalization and potential cardiovascular and reproductive harms. These warnings do not provide a reliable compound-specific incidence rate, but they rule out presenting the category as an established safe alternative. Jaundice, dark urine or concerning abdominal symptoms warrant medical assessment; chest pain or sudden severe breathlessness needs urgent care.^[9]

POWER1 and POWER2 studied approximately 325 participants each with advanced non-small-cell lung cancer receiving chemotherapy. The sponsor's 2013 report described oral enobosarm 3 mg daily versus placebo. Neither trial met its overall prespecified day-84 coprimary responder criteria. These results come from a sponsor release filed with the SEC, not a full peer-reviewed results paper assessed here.^[5]

A responder analysis asks how many participants cross a defined threshold. A continuous analysis uses the size of measured changes. Differences between them are possible without implying misconduct or mathematical contradiction. The problem would be choosing whichever result is favorable after seeing the data and presenting it as success on the original clinical question.

For that reason, the accurate conclusion is more precise than “all function results failed.” The prespecified functional-responder findings were nonsignificant in both trials; the alternative continuous analysis was positive in one and not the other. The overall coprimary criteria were not met.^[5]

Cancer and chemotherapy introduce constraints that are absent from a healthy training setting. These trials therefore do not prove that a healthy lifter cannot gain muscle. They do show why a lean-mass effect cannot be assumed to produce meaningful function across populations. The intended clinical benefit must survive a direct test.

The JAMA analysis also detected other investigational agents in products marketed as SARMs. A retail category is not a pharmacological definition: compounds sold alongside androgen-receptor modulators do not necessarily share that receptor mechanism. PubMed links a 2018 correction titled “Omitted Conflict of Interest Disclosures”; the full correction text was not accessible in this review.^[8][10]

This creates two uncertainties for an anecdote. First, did the person experience an effect attributable to the named molecule? Second, did the product actually deliver that molecule in the claimed amount? Training, nutrition, expectations and other exposures add further uncertainty. A vivid report can generate a worthwhile hypothesis without supplying a trustworthy response rate.

Product uncertainty should not be used to explain away every adverse event as contamination. Nor should every reaction to an unverified mixture be assigned confidently to one named SARM. Both shortcuts exceed the available identification. The sound approach records what was tested, what was measured and what remains unknown.

Even perfect product identity would not resolve the clinical evidence gaps. Analytical purity and demonstrated long-term benefit are different claims. A chemical analysis cannot establish durable hypertrophy, fertility preservation or cardiovascular safety. Those require appropriate human outcomes.

Enobosarm is now being studied alongside GLP-1 treatment in older adults with obesity. Veru reports favorable body-composition findings from its 168-participant QUALITY trial. Those sponsor summaries are encouraging development signals, not evidence that enobosarm has an established benefit for healthy bodybuilding or an approved indication.^[6]

The September 8, 2026 sponsor update describes PLATEAU participants aged at least 65 with BMI at least 35, receiving semaglutide plus enobosarm or placebo. Fat mass, lean mass, stair-climbing function and bone measurements are among secondary endpoints. This is a test of a combination in a defined clinical population, not a general demonstration of SARM selectivity.^[7]

Preserving tissue during weight loss and adding tissue during resistance training are related ambitions, but they are not the same experiment. A positive result in the former could matter greatly without quantifying the latter. Similarly, a change in total weight can conceal different combinations of fat and lean tissue; the component measurements remain essential.

Regulatory conversations, enrollment milestones and patents do not constitute approval. As checked October 30, 2026, the FDA's current communication continues to describe SARMs products as unapproved. This article does not turn projected 2027 readouts into completed evidence.^[9][7]