Abstract. LGD-4033 (ligandrol) is a nonsteroidal selective androgen receptor modulator (SARM) developed to provide anabolic benefits (increase lean body mass and strength) with reduced androgenic side effects compared with traditional androgens. Early phase human trials demonstrated dose-dependent increases in lean mass and favorable pharmacokinetics, but safety data remain limited and case reports and systematic reviews have raised concerns about hepatotoxicity, endocrine disruption, and the risks of unregulated products. LGD-4033 is prohibited in sport by WADA and remains an investigational compound, not approved for clinical use outside trials. Wada-Ama+3PubMed+3PMC+3

1. Background and development

LGD-4033 is a potent oral SARM developed to selectively activate androgen receptors in muscle and bone while sparing prostate and other androgen-sensitive tissues. SARMs were explored to treat sarcopenia, cachexia, osteoporosis and other wasting conditions where anabolic activity is desirable but classical anabolic steroids produce unacceptable side effects. Translational Andrology and Urology

2. Mechanism of action

LGD-4033 binds the androgen receptor (AR) and acts as a tissue-selective agonist: in skeletal muscle and bone it recruits coactivators that increase anabolic signaling (protein synthesis, satellite cell activity), while having reduced stimulation of AR-regulated genes in prostate and sebaceous tissues. This tissue selectivity underlies the therapeutic rationale for SARMs. Translational Andrology and Urology

3. Key human clinical evidence

• Phase 1 / randomized trials: A placebo-controlled randomized trial of LGD-4033 in healthy men (up to 21 days) reported favorable pharmacokinetics, dose-dependent increases in lean body mass, and no change in prostate-specific antigen during the short study period. The trial supported further clinical investigation but was small and short duration. PubMed
• Meta / systematic reviews: Systematic reviews of SARMs (including LGD-4033) summarize evidence from multiple small trials and note anabolic effects on lean mass but emphasize that long-term efficacy and safety have not been established. PMC+1

Taken together, clinical signals for anabolic effect exist in short trials, but larger and longer randomized controlled trials on clinically relevant outcomes (function, morbidity, long-term safety) are lacking. PMC

4. Safety signals and adverse events

• Hepatotoxicity / drug-induced liver injury (DILI): Multiple case reports and case series have described clinically significant liver injury associated with off-label LGD-4033 use; these include cholestatic and mixed patterns of liver injury. While early controlled trials reported no significant ALT/AST elevations in short exposure, real-world use (often higher doses, longer duration, or contaminated products) has been associated with liver injury. PMC+1
• Endocrine suppression: Like other potent androgenic agents, SARMs can suppress endogenous hypothalamic-pituitary-gonadal axis (reduced LH/testosterone) after exposure; the magnitude and duration depend on dose and duration. PMC
• Product quality / contamination risks: Many LGD-4033 products sold online are mislabelled, vary in purity, or contain other undeclared substances; such variability increases safety risks. Urine/metabolism studies have characterized LGD-4033 metabolites to support detection and forensic analyses. PubMed+1

Because of these concerns, clinical use outside controlled trials is not recommended. PMC

5. Regulatory and anti-doping status

LGD-4033 is not FDA-approved for clinical use. The World Anti-Doping Agency (WADA) lists LGD-4033 (and other SARMs) on the Prohibited List — use is banned at all times for athletes. Anti-doping agencies and sporting bodies treat LGD-4033 as an anabolic agent with strict sanctions for positive tests. Wada-Ama+2Wada-Ama+2

6. Gaps and research priorities

• Longer randomized controlled trials assessing functional outcomes, optimal dosing, and long-term safety. PMC
• Systematic pharmacovigilance to quantify risks of hepatotoxicity and endocrine effects in real-world use. PMC
• Standardized manufacturing and quality controls for any clinical formulation to avoid product variability. PubMed

10-Question FAQ (concise)

1. What is LGD-4033 (Ligandrol)?
   LGD-4033 is an oral selective androgen receptor modulator (SARM) developed to increase lean mass and muscle strength with fewer androgenic side effects than traditional anabolic steroids. Translational Andrology and Urology
2. Has it been tested in humans?
   Yes — early phase trials (including randomized placebo-controlled studies) showed dose-dependent increases in lean mass and favorable pharmacokinetics in short-term studies. Larger and longer trials are still needed. PubMed+1
3. Is LGD-4033 legal / FDA approved?
   No — LGD-4033 is investigational and not FDA-approved for general clinical use. It is often sold online as a “research chemical” or supplement (which raises regulatory and safety issues). PMC
4. Is LGD-4033 banned in sport?
   Yes. WADA classifies LGD-4033 as a prohibited anabolic agent; it is banned at all times for athletes. Positive tests carry sanctions. Wada-Ama+1
5. What are the main safety risks?
   Reported risks include liver injury (DILI), endocrine suppression (reduced natural testosterone), and other adverse effects; many reports are from off-label or unregulated product use. PMC+1
6. Can LGD-4033 increase muscle mass?
   Short trials show increases in lean body mass, but clinical benefits on strength, function, or long-term outcomes remain incompletely characterized. PubMed+1
7. How is LGD-4033 detected?
   Metabolism and excretion studies describe LGD-4033 metabolites useful for urine testing; anti-doping labs can detect ligandrol for days to weeks depending on dose and assay sensitivity. PubMed+1
8. Are online products reliable?
   Not reliably. Many consumer products are mislabeled, contaminated or of unknown purity. This adds significant safety risk. PMC
9. What should clinicians watch for?
   Elevated liver enzymes, jaundice, symptoms of hepatic injury, suppressed testosterone/LH, and unexplained changes in lipids or mood — especially with self-reported use of SARMs. Consider asking about supplement use when seeing compatible complaints. PMC+1
10. What research is still needed?
    Well-powered RCTs that measure functional outcomes and long-term safety, standardized formulations for human trials, and population surveillance for adverse events. PMC

Selected citations / links (PubMed / PMC)

• 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. Journals of Gerontology A. 2013. (Phase I clinical trial). PubMed+1
• Vignali JD, et al. Systematic review of safety of selective androgen receptor modulators. (2023). (Summarizes trial safety signals across SARMs). PMC
• Barbara M, et al. Ligandrol (LGD-4033)-induced liver injury. Case reports / review — evidence of real-world hepatotoxicity. 2020 & 2024 case literature. PMC+1
• Fragkaki AG, et al. Human in vivo metabolism study of LGD-4033. (Metabolite/excretion data useful for detection). 2018. PubMed
• World Anti-Doping Agency (WADA). Prohibited List — SARMs (including LGD-4033) prohibited. Wada-Ama+1

(If you want a printable bibliography with PMIDs/DOIs, I can generate that next.)

SEO & metadata suggestions (webpage / article)

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Short practical disclaimer

This summary is for educational and research purposes only, not medical advice. LGD-4033 is investigational and not FDA-approved; clinical use should be limited to authorized studies. Athletes must avoid LGD-4033 — it is prohibited by WADA and can lead to sanctions.