Ligandrol (LGD-4033)

Overview

Ligandrol (LGD-4033) is a nonsteroidal selective androgen receptor modulator (SARM) of the substituted pyrrolidinyl-benzonitrile chemotype. It has been tested in Phase 1 and Phase 2 clinical trials for muscle wasting and hip-fracture recovery but has no FDA-approved medical use anywhere. LGD-4033 is prohibited at all times (in- and out-of-competition) under WADA Prohibited List section S1.2, “Other Anabolic Agents” (SARMs class). It is sold online as an unregulated “research chemical” of unverified purity and dose.

Mechanism of Action

LGD-4033 binds the androgen receptor ligand-binding domain with high affinity (Ki ≈ 1 nM) and selectivity, driving muscle- and bone-selective transcriptional activation. Preclinical models demonstrate anabolic activity in muscle and anti-resorptive/anabolic activity in bone, with reduced activity in prostate tissue relative to classical androgens. The compound shows tissue-selective agonism, though this selectivity is lost at high doses in animal studies.

Research Summary

Human data are limited to investigational trials and case reports; no approved medical use exists. A Phase 1 randomized, double-blind, placebo-controlled trial (Basaria et al. 2013, N=76 healthy men aged 21–50) tested 0.1, 0.3, and 1.0 mg/day for 21 days and found dose-dependent increases in lean body mass, with dose-dependent suppression of testosterone, SHBG, HDL cholesterol, and triglycerides that normalized after stopping. A Phase 2 trial (VK5211, N=108 hip-fracture-recovery patients, 0.5–2.0 mg/day for 12 weeks) reported via press release placebo-adjusted lean-mass increases of 4.8–9.1% with no drug-related serious adverse events; this result has not been peer-reviewed. Published case reports document severe cholestatic hepatitis (total bilirubin 35.0 mg/dL) in a 32-year-old male after ∼10 mg/day for ∼2 weeks—a dose 10–100× higher than trial doses—and marked testosterone suppression (−62.3%), elevated liver enzymes (ALT +205%, AST +96%), and adverse lipid changes in a 25-year-old male using 10 mg/day for 5 weeks; both cases involved unsupervised gray-market product. In ovariectomized rats (osteoporosis model), oral LGD-4033 at 0.04–4 mg/kg/day for 5 weeks increased muscle capillary density at all doses, elevated oxidative enzymes at intermediate doses, and increased muscle fiber cross-sectional area at the highest dose, but also increased intramuscular fat and uterine weight at 4 mg/kg, indicating loss of tissue selectivity at high exposure.

Prescribers who offer Ligandrol (LGD-4033)

2 prescribers in our directory work with Ligandrol (LGD-4033), each confirmed from their own website. Peptides like Ligandrol (LGD-4033) require a prescription from a licensed provider.

Reported Side Effects

• Dose-dependent suppression of total testosterone, SHBG, HDL cholesterol, and triglycerides (Phase 1 trial; normalized after discontinuation)
• Severe cholestatic hepatitis (total bilirubin 35.0 mg/dL) in case report at ~10 mg/day for ~2 weeks (10–100× trial doses)
• Marked testosterone suppression (−62.3%), elevated liver enzymes (ALT +205%, AST +96%), adverse lipid changes in case report at 10 mg/day for 5 weeks
• Prohibited at all times by WADA under S1.2 (SARMs class); detectable by LC-MS/MS
• Unregulated gray-market product of unverified purity and dose

Compare Ligandrol (LGD-4033) with Others

Research References

• The safety, pharmacokinetics, and effects of LGD-4033, a novel nonsteroidal oral, selective androgen receptor modulator, in healthy young men (Basaria S, et al.). 2013. PMID 22459616.
• Ligandrol (LGD-4033)-Induced Liver Injury (Barbara M, Dhingra S, Mindikoglu AL) — ACG Case Reports Journal. 2020.
• LGD-4033 and MK-677 use impacts body composition, circulating biomarkers, and skeletal muscle androgenic hormone and receptor content: A case report (Cardaci TD, et al.) — Experimental Physiology. 2022. PMID 36303408.
• Ostarine and Ligandrol Improve Muscle Tissue in an Ovariectomized Rat Model (Roch PJ, et al.) — Frontiers in Endocrinology. 2020.

Frequently asked questions

Has Ligandrol (LGD-4033) been independently lab-tested?

Disclosed Labs has collected 2 Certificates of Analysis (COA) for Ligandrol (LGD-4033) from 1 independent testing lab. 1 vendor has submitted material for testing. Products average 99.4% tested purity across the corpus. Full testing data is available at https://www.disclosedlabs.com/peptides/lgd-4033/testing.

Which prescribers offer Ligandrol (LGD-4033) with a prescription?

2 prescribers in the Disclosed Labs directory work with Ligandrol (LGD-4033), each confirmed from their own website. Ligandrol (LGD-4033) requires a prescription from a licensed provider. Browse them at https://www.disclosedlabs.com/prescribers?peptide=Ligandrol%20(LGD-4033).

How does Ligandrol (LGD-4033) work?

LGD-4033 binds the androgen receptor ligand-binding domain with high affinity (Ki ≈ 1 nM) and selectivity, driving muscle- and bone-selective transcriptional activation. Preclinical models demonstrate anabolic activity in muscle and anti-resorptive/anabolic activity in bone, with reduced activity in prostate tissue relative to classical androgens. The compound shows tissue-selective agonism, though this selectivity is lost at high doses in animal studies.

What does the research say about Ligandrol (LGD-4033)?

Human data are limited to investigational trials and case reports; no approved medical use exists. A Phase 1 randomized, double-blind, placebo-controlled trial (Basaria et al. 2013, N=76 healthy men aged 21–50) tested 0.1, 0.3, and 1.0 mg/day for 21 days and found dose-dependent increases in lean body mass, with dose-dependent suppression of testosterone, SHBG, HDL cholesterol, and triglycerides that normalized after stopping. A Phase 2 trial (VK5211, N=108 hip-fracture-recovery patients, 0.5–2.0 mg/day for 12 weeks) reported via press release placebo-adjusted lean-mass increases of 4.8–9.1% with no drug-related serious adverse events; this result has not been peer-reviewed. Published case reports document severe cholestatic hepatitis (total bilirubin 35.0 mg/dL) in a 32-year-old male after ∼10 mg/day for ∼2 weeks—a dose 10–100× higher than trial doses—and marked testosterone suppression (−62.3%), elevated liver enzymes (ALT +205%, AST +96%), and adverse lipid changes in a 25-year-old male using 10 mg/day for 5 weeks; both cases involved unsupervised gray-market product. In ovariectomized rats (osteoporosis model), oral LGD-4033 at 0.04–4 mg/kg/day for 5 weeks increased muscle capillary density at all doses, elevated oxidative enzymes at intermediate doses, and increased muscle fiber cross-sectional area at the highest dose, but also increased intramuscular fat and uterine weight at 4 mg/kg, indicating loss of tissue selectivity at high exposure.