LGD-4033 — Background and Chemical Identity

• Chemical name / synonyms: LGD-4033; Ligandrol; VK‑5211; Anabolicum. Wikipedia+2Analytical Science Journals+2
• CAS number: 1165910‑22‑4 Wikipedia
• Mechanism of action: LGD-4033 is a non‑steroidal selective androgen receptor modulator (SARM). It binds the androgen receptor (AR) with high affinity (K_i ≈ 0.9–1 nM) and exhibits tissue selectivity — agonistic effects in muscle and bone, with relatively lower activity in e.g. prostate or other classical androgen‑sensitive tissues. Wikipedia+2ResearchGate+2
• Intended / investigated therapeutic uses (preclinical / early clinical): Originally developed for conditions involving muscle-wasting (cachexia), age‑related muscle loss (sarcopenia), bone loss / osteoporosis, and recovery from fractures or disuse. Ligand Investor Relations+2The University of Sydney+2

Research Evidence: Pharmacokinetics, Effects, and Metabolism

• In a randomized, double-blind, placebo-controlled Phase I study in healthy young men (21–50 y), daily oral doses of 0.1, 0.3, or 1.0 mg LGD‑4033 for 21 days increased lean body mass in a dose-dependent manner, with no significant change in prostate‑specific antigen (PSA), liver enzymes (AST/ALT), hematology, or ECG parameters. ResearchGate+2PMC+2
• The study also documented dose-dependent suppression of total testosterone, sex hormone‑binding globulin (SHBG), HDL cholesterol, and triglycerides during treatment; free testosterone and follicle-stimulating hormone (FSH) were significantly suppressed only at the 1.0 mg dose. PMC+2PubMed+2
• Upon discontinuation, hormone levels and lipids returned toward baseline in that short-term study. PMC+1
• Metabolism and excretion: Human in vivo studies and analytical research have characterized multiple phase‑I metabolites in urine and plasma, and long‑term (“bishydroxylated”) metabolites have been chemically synthesized for reference and doping‑control purposes. SpringerLink+2RSC Publishing+2
• Detection: Because of its misuse in sports, labs have developed sensitive LC–MS/MS and LC–HRMS/MS methods that can detect LGD‑4033 and its metabolites at very low levels (e.g., detection limits in the picogram/mL range) in urine. PMC+1

Potential Benefits (Based on Preclinical and Early Human Data)

• Increase in lean body mass / muscle mass — As shown in the 21‑day Phase I study in healthy men. ResearchGate+2PubMed+2
• Potential bone-anabolic / bone-preserving effects — Preclinical (animal) studies reportedly showed increased bone formation, bone mineral density, and bone strength in bone-loss models (e.g., ovariectomized rats), suggesting possible utility in osteoporosis or fracture recovery. Ligand Investor Relations+2The University of Sydney+2
• Tissue selectivity (muscle and bone over prostate / non-skeletal tissues) — The design of LGD-4033 aims to deliver anabolic benefits with a reduced risk of classical androgenic side effects (e.g. prostate hypertrophy). Ligand Investor Relations+2Wikipedia+2
• Favorable pharmacokinetic profile (oral bioavailability, reasonable half-life) — The phase I study reported a long elimination half-life, and accumulation with repeated dosing, which may be convenient for dosing in a clinical context. PMC+1
• Therapeutic potential in muscle‑wasting conditions — Given the above, LGD-4033 has been proposed as a candidate for treatment of sarcopenia, cachexia, osteoporosis, and other catabolic conditions affecting muscle/bone. Healthy Male+2Ligand Investor Relations+2

Known Risks, Concerns, and Limitations

• Hormonal suppression — Clinical data show dose-dependent reductions in total testosterone, free testosterone, SHBG, FSH, and unfavorable changes in lipid profile (HDL ↓, triglycerides ↓) during administration. PMC+2Wikipedia+2
• Unknown long-term safety — There is a lack of medium- and long-term clinical trials. As noted by regulators and experts, the long-term health impacts (especially with higher doses, prolonged use, or off-label use) remain unknown. Sport Integrity Australia+2U.S. Food and Drug Administration+2
• Liver toxicity / hepatotoxicity (especially off-label / high-dose use) — Although early clinical trials reported no significant change in liver enzymes, there are multiple case reports linking non‑medical use of LGD-4033 to drug-induced liver injury (DILI), including severe liver damage. PMC+2Lippincott Journals+2
• Cardiovascular risk — Regulatory bodies have warned that use of SARMs (including LGD-4033) may increase the risk of heart attack or stroke, due to effects on lipid profile and other unknown mechanisms. U.S. Food and Drug Administration+2Wikipedia+2
• Potential psychiatric / other systemic adverse effects — Reports have included sleep disturbances, psychosis/hallucinations, sexual dysfunction, possible infertility, testicular shrinkage, and other endocrine or systemic effects — especially in non‑clinical / recreational use contexts. U.S. Food and Drug Administration+2Cleveland Clinic+2
• Regulatory status and misuse risk — LGD‑4033 is not approved for medical use by the U.S. Food and Drug Administration (FDA) or other major regulatory agencies; products marketed as dietary supplements containing LGD‑4033 are considered unapproved new drugs. NPC Hello+2WebMD+2
• Risks greater with off-label use, higher doses, or prolonged use — Many of the adverse events (e.g., liver injury) are reported in the context of non‑medical high-dose or prolonged use — conditions not studied in controlled trials. Lippincott Journals+2PMC+2
• Potential athletic doping consequences — World Anti‑Doping Agency (WADA) prohibits LGD‑4033; it is classified under “other anabolic agents.” Use by athletes may result in doping violations. NPC Hello+2Wada Ama+2

Why “Injectable LGD-4033” Is Particularly Problematic / Unsupported

• All published human clinical studies of LGD-4033 to date have used oral administration. ResearchGate+2Ligand Investor Relations+2
• There is no public clinical or preclinical evidence about safety, pharmacokinetics, or efficacy of injectable LGD-4033 (or SARM solutions for injection). Therefore any claims about “injectable LGD-4033” are not supported by peer‑reviewed data.
• Off-label or black‑market formulations (especially injectable) pose additional risks: contamination, dosing errors, sterility issues, unknown side effects, and increased risk of serious adverse events. Regulatory warnings flag such use as dangerous. WebMD+2Sport Integrity Australia+2

Summary / Conclusion (as of current research)

LGD‑4033 is a potent, tissue-selective SARM which, in short-term human clinical trials, demonstrated increased lean body mass and a favorable tolerability profile over 21 days. Preclinical data suggest potential bone‑anabolic effects. However, benefits come with trade‑offs: hormonal suppression, lipid changes, and — especially when misused off‑label (higher doses or longer durations) — serious risks such as liver injury or cardiovascular events. Importantly, long-term safety remains unknown, and LGD-4033 is not approved for clinical use.

Given the uncertainties and known risks — especially outside controlled research settings — any non‑clinical use (especially injectable formulations) is highly risky and not supported by scientific evidence.

For research use only. This document does not constitute medical advice or a recommendation for non-approved use.

Frequently Asked Questions (FAQs) about LGD‑4033

1. What is LGD‑4033, and what is its CAS number?
   • LGD‑4033 (Ligandrol, VK‑5211) is a selective androgen receptor modulator (SARM). Its CAS number is 1165910‑22‑4. Wikipedia+1
2. Is LGD‑4033 legally approved for muscle building or bodybuilding?
   • No. LGD‑4033 has not been approved by the FDA or equivalent medical regulators for muscle building, bodybuilding, or general use. It remains experimental. NPC Hello+2WebMD+2
3. What evidence is there for muscle or lean‑mass gain with LGD‑4033?
   • In a randomized, placebo-controlled study in healthy men given 0.1–1.0 mg/day for 21 days, participants showed a dose-dependent increase in lean body mass without significant adverse events over that short period. ResearchGate+2PMC+2
4. Could LGD‑4033 help with bone health or osteoporosis?
   • Preclinical (animal) studies suggested LGD‑4033 may increase bone formation, bone density, and strength — indicating possible therapeutic potential in bone-wasting conditions or osteoporosis. Ligand Investor Relations+2Healthy Male+2
   • However, human data are limited; there is no robust clinical evidence confirming bone‑health benefits in humans.
5. What are the main risks or side effects observed in studies or case reports?
   • Hormonal disruption: decreases in total and free testosterone, SHBG, FSH, with lipid profile changes (e.g., lower HDL). PMC+2Wikipedia+2
   • Liver injury: while early trials reported no liver enzyme elevation, there are multiple case reports linking LGD‑4033 misuse to drug-induced liver injury (DILI), sometimes severe. PMC+2Lippincott Journals+2
   • Potential cardiovascular risk: due to lipid profile changes and other unknown long-term effects, use of SARMs including LGD-4033 has been associated with increased risk of heart attack or stroke (as per regulatory warnings). U.S. Food and Drug Administration+2Wikipedia+2
   • Other adverse effects (especially in non‑clinical use): sexual dysfunction, infertility, sleep disturbances, psychiatric symptoms, testicular shrinkage, etc. U.S. Food and Drug Administration+2Cleveland Clinic+2
6. Has LGD‑4033 been studied long-term in humans?
   • No. Published human trials are short-term (e.g., 21 days) or small, and there is a lack of medium- / long-term data. Sport Integrity Australia+2Wikipedia+2
   • Consequently, long-term safety, especially with prolonged dosing, higher doses, or off-label usage, remains uncertain.
7. Is “injectable LGD‑4033” a studied or safe form of administration?
   • No. All published human data use oral administration. There is no peer-reviewed evidence about safety, pharmacokinetics, or efficacy of injectable LGD‑4033. Any claims otherwise are unsupported by scientific literature.
8. How is LGD‑4033 detected (or tested) in doping control or research settings?
   • Analytical methods using liquid chromatography–mass spectrometry (LC–MS/MS or LC–HRMS/MS) have been developed to detect LGD‑4033 and its metabolites in urine (and plasma) at very low concentrations — even after micro-doses. PMC+2SpringerLink+2
   • Long-term metabolites (e.g., a bishydroxylated derivative) have been chemically synthesized to serve as reference standards for doping control. RSC Publishing+2Wada Ama+2
9. Why do regulatory bodies warn against using LGD‑4033?
   • Because of the risks of liver injury, cardiovascular problems, hormone disruption, and the lack of long-term safety data. Moreover, LGD‑4033 is not approved for human therapeutic use or as a dietary supplement. Cleveland Clinic+3U.S. Food and Drug Administration+3WebMD+3
   • Use for athletic performance enhancement violates doping regulations (e.g., by World Anti‑Doping Agency — WADA). NPC Hello+2Wada Ama+2
10. Given what we know: is LGD‑4033 “worth it” for research or therapeutic development?
    • As a research compound, LGD-4033 remains of interest because of its tissue-selective AR agonism, anabolic potential on muscle and bone, and preliminary tolerability. Controlled, long-term clinical trials would be required to thoroughly evaluate safety, dose‑response, efficacy, and risk/benefit balance for any therapeutic indication.
    • However, as of now, the risks — particularly for off-label or non-medical use — appear substantial, and long-term consequences are unknown.

References (Key Studies / Reviews)

• Basaria S., Wilson L., Dillon E. L., et al. “The Safety, Pharmacokinetics, and Effects of LGD‑4033, a Novel Nonsteroidal Oral Selective Androgen Receptor Modulator, in Healthy Young Men.” The Journals of Gerontology Series A, 2013. (PubMed) ResearchGate+2PubMed+2
• Pitsinos E. N., Angelis Y. S., Petrou M. “Structure revision and chemical synthesis of ligandrol’s main bishydroxylated long-term metabolic marker.” Org. Biomol. Chem., 2022. RSC Publishing
• Wagener F., Thevis M., et al. “Investigations into the elimination profiles and metabolite pattern of LGD-4033 in human plasma and urine.” 2022. (LC–HRMS/MS study) SpringerLink
• Labban H. et al. “LGD-4033 and a Case of Drug‑Induced Liver Injury.” 2024. (Case report) PMC
• Vignali J. D. et al. “Systematic Review of Safety of Selective Androgen Receptor Modulators in Healthy Adults: Implications for Recreational Users.” 2023. (Review summarizing SARM safety) MDPI+1
• FDA — Public Warnings on SARMs (on risks, unapproved status) U.S. Food and Drug Administration+1
• Additional context on SARM pharmacology, misuse risk, and regulatory status. Wikipedia+2Wikipedia+2

Disclaimer

This document is provided for research and educational purposes only. LGD‑4033 is not approved by regulatory authorities for muscle building, bodybuilding, or general human use. The safety and efficacy of LGD-4033 (especially in off-label or non‑clinical contexts such as injectable use) remain unproven. Use of LGD‑4033 outside controlled research settings carries significant health risks.