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Anabolic & Androgenic

LGD-4033 (Ligandrol)

Oral SARM that builds lean mass in small trials but suppresses natural testosterone, lowers HDL, and has case reports of liver injury.

RestrictedEvidence level 3 of 5: Limited human dataAlso: Ligandrol, VK5211, Anabolicum

Overview

LGD-4033 is a nonsteroidal selective androgen receptor modulator designed to deliver the muscle- and bone-building effects of androgens with less impact on prostate and skin. In a 21-day Phase 1 trial in healthy men, even low doses increased lean body mass by about 1 kg, while suppressing total testosterone, SHBG and HDL in a dose-dependent way. A Phase 2 study in older adults recovering from hip fracture showed lean-mass gains but development did not proceed to approval. Outside trials, it is sold illegally online at much higher doses, and case reports describe drug-induced liver injury. 'Selective' does not mean free of endocrine effects: suppression of the natural testosterone axis is consistent.

Classification
Nonsteroidal selective androgen receptor modulator (SARM) — small molecule, not a peptide
Route
Oral
Half-life
~24–36 hours (oral)

Mechanism of action

Primary targetAndrogen receptor (tissue-selective agonist)
  1. Oral absorptionWell absorbed orally with a long half-life allowing once-daily dosing.
  2. Androgen receptor bindingBinds the androgen receptor with high affinity and selectivity.
  3. Tissue-selective coactivator recruitmentRecruits coactivators preferentially in muscle and bone versus prostate.
  4. Anabolic transcriptionUpregulates muscle protein synthesis and bone formation genes.
  5. Axis suppressionCentral androgen signaling lowers LH, FSH and endogenous testosterone.
Downstream effects
  • Lean mass gain
  • Testosterone and HDL suppression
  • Possible bone support

Researched for

  • Muscle wasting and cachexia
  • Sarcopenia
  • Hip-fracture recovery
  • Osteoporosis (preclinical)

Research notes

  • Basaria et al. (J Gerontol, 2013): Phase 1 RCT, 76 healthy men, three low doses for 21 days; dose-dependent lean-mass gain with testosterone, SHBG and HDL suppression.
  • Phase 2 (VK5211) in hip-fracture patients reported lean-mass gains at 12 weeks; no Phase 3 or approval followed.
  • Multiple published case reports of drug-induced liver injury (cholestatic hepatitis) with non-prescribed SARM use.
  • Products sold online are frequently mislabeled or contain other substances (JAMA 2017 analysis of SARM products).

Reported side effects

  • Suppression of natural testosterone (requires PCT)
  • HDL reduction, LDL elevation
  • Liver enzyme elevation; reported liver injury
  • Water retention
  • Possible cardiovascular strain

Contraindications & cautions

  • Women who are or may become pregnant; adolescents
  • Liver disease
  • Cardiovascular disease or dyslipidemia
  • Prostate or breast cancer
  • Competitive athletes subject to drug testing

Lab monitoring

  • CBC with differential
  • CMP with liver enzymes (AST, ALT, ALP, GGT, bilirubin)
  • Fasting lipid panel
  • Total and free testosterone, estradiol, LH, FSH, SHBG
  • PSA (men >40)
  • Fasting glucose, HbA1c, hsCRP
  • Baseline ECG if cardiac risk or >40

Dosing and pricing for LGD-4033 (Ligandrol)

Dosing references and compound pricing are available to established patients in the secure portal after a medical evaluation.

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