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Hepatotoxic

Ligandrol

LGD-4033 · VK5211

Ligandrol (LGD-4033, VK5211) is an orally active, non-steroidal selective androgen receptor modulator (SARM) originally developed for muscle-wasting and osteoporosis and now widely misused for muscle building despite having no FDA approval and no approval for any human indication. It is not a "safe steroid alternative." The only randomized human trial was tiny, lasted just 21 days, and used doses (0.1-1.0 mg/day) far below the 5-10 mg/day amounts commonly self-administered; at those low doses it still suppressed testosterone, SHBG, HDL cholesterol and triglycerides. At real-world recreational doses there is essentially no controlled human safety data. The main risks, documented in case reports, are severe drug-induced liver injury (including cholestatic hepatitis with jaundice), suppression of the hypothalamic-pituitary-testicular axis (endogenous testosterone shutdown), and adverse lipid/cardiovascular changes. Products sold as "Ligandrol" are frequently mislabeled, underdosed, overdosed, or contaminated with other SARMs or anabolic steroids. Anyone using it should treat it as an experimental, unmonitored drug and involve a physician.

Clinical readoutSARM · sarm
Hepatic strainHigh
CardiovascularModerate
HPTA suppressionHigh
Half-life
30 h
Route
Oral
Evidence
C
Active
Consistent with once-da…
30 h2.5 d3.8 d5 d6.3 d
Illustrative single-compartment washout · each mark = one half-life · t½ ≈ Long terminal elimination half-life, reported on the order of ~24-36 hours in the phase 1 human study, supporting once-daily dosing.
Pharmacology

Mechanism of action

LGD-4033 is a high-affinity, non-steroidal ligand of the androgen receptor (AR). It acts as a tissue-selective AR agonist, producing anabolic (agonist) effects in muscle and bone while exerting relatively weaker androgenic activity in tissues such as the prostate, which is the rationale behind the "selective" designation. Downstream, AR activation drives androgen-responsive gene transcription that increases muscle protein accretion and lean body mass. Because it activates the same AR-mediated negative feedback on the hypothalamic-pituitary-testicular axis as testosterone, it dose-dependently suppresses endogenous gonadotropins and testosterone. It is non-aromatizable (not converted to estrogen) and is not a 17-alpha-alkylated steroid, though it still carries demonstrated hepatotoxic potential.
Kinetics

Pharmacokinetics

Half-life

Long terminal elimination half-life, reported on the order of ~24-36 hours in the phase 1 human study, supporting once-daily dosing.

Active duration

Consistent with once-daily oral dosing; multiple-dose administration produced dose-proportional accumulation with approach to steady state over roughly 1-3 weeks. Parent drug and metabolites remain detectable in urine and hair for an extended period after cessation (relevant only for clinical monitoring/washout, not for evading testing).

Route

Oral (administered as a solution/capsule in studies; recreationally taken orally).

Metabolism & clearance

Hepatically metabolized to multiple phase I metabolites (including a characterized epimer, M1); metabolites are excreted in urine. Extensive hepatic handling is consistent with the observed potential for liver injury. Long detection windows in urine and hair reflect slow clearance of parent and metabolites.

For monitoring and washout planning, not drug-test evasion.

Reported effects

Physiological & performance effects

  • Dose-dependent increase in lean body mass over 21 days in healthy young men, without significant change in fat mass at the low doses studied (up to 1.0 mg/day)
  • Dose-dependent suppression of total testosterone and sex hormone-binding globulin (SHBG); free testosterone and FSH significantly suppressed at the 1.0 mg dose
  • Reductions in HDL cholesterol and triglycerides during administration in the trial (values returned toward baseline after discontinuation)
  • In a real-world case of higher-dose use (10 mg/day with MK-677), increases in body mass, lean mass and also fat mass, plus marked strength gains, alongside adverse lipid, liver-enzyme, bone and hormonal changes
  • No significant change in prostate-specific antigen (PSA), hemoglobin, or QT interval at the low doses and short duration studied — this does not establish safety at higher recreational doses or longer durations
Safety

Adverse effects by system

Cardiovascular

Adverse lipid changes are the best-documented cardiovascular-relevant effect: dose-dependent lowering of HDL cholesterol in the 21-day RCT, and in a higher-dose real-world case a large HDL drop (~36%) with rises in LDL and triglycerides. Sustained atherogenic lipid shifts are a plausible cardiovascular risk. No controlled data on hard cardiovascular outcomes exist; safety reviews and forensic reports note theoretical/associated risks of myocardial infarction and thrombosis with SARM misuse, but causation is not established.

Hepatic

Serious concern. Multiple case reports document drug-induced liver injury, including biopsy-confirmed cholestatic hepatitis with fibrosis and cases of pruritic jaundice after weeks-to-months of use. Reversible ALT/AST elevations were reported in a co-administration case and across SARM safety reviews. Liver enzymes did not rise in the short low-dose RCT, so hepatotoxicity appears related to higher doses/longer duration or idiosyncratic susceptibility.

Endocrine / HPTA

Marked and expected. Dose-dependent suppression of total testosterone, free testosterone (at 1.0 mg), SHBG and FSH via AR-mediated negative feedback. In the low-dose short trial, hormones recovered after discontinuation; at higher recreational doses and longer durations the degree and reversibility of suppression are not well characterized.

Reproductive

Suppression of the testicular axis lowers endogenous testosterone and gonadotropins, which can reduce spermatogenesis and impair fertility while active; recovery timelines at recreational doses are not well defined. No dedicated human fertility studies. Contraindicated in pregnancy given androgenic/teratogenic potential; no human pregnancy data.

Neuropsychiatric

Limited data. General SARM safety reviews list psychiatric/mood disturbances among reported off-label adverse effects, but there is no adequate controlled human data specific to LGD-4033; androgenic agents can affect mood, libido and irritability. Treat as an under-characterized risk.

Renal

No specific nephrotoxic signal identified in the human trial. Rhabdomyolysis has been reported with SARMs as a class, which can secondarily threaten renal function; no direct renal injury attributable to LGD-4033 is established. Overall: limited/no adequate human data on renal effects.

Hematologic

No significant change in hemoglobin at the low doses/short duration in the RCT. Androgen receptor agonists can raise hemoglobin/hematocrit (polycythemia risk) at higher exposures; forensic literature raises theoretical clotting concerns. Direct hematologic toxicity from LGD-4033 at recreational doses is not adequately characterized.

Dermatologic

Limited data. Androgenic dermatologic effects (acne, oily skin, possible hair changes) are biologically plausible for an AR agonist but were not systematically reported in the trial; jaundice-associated pruritus occurred in a hepatotoxicity case. No adequate human data specific to LGD-4033 skin effects.

Recovery

HPTA suppression & recovery

Suppression: Significant and dose-dependent — suppresses total and (at higher doses) free testosterone, SHBG and FSH

In the low-dose 21-day trial, hormone levels returned toward baseline within about 5 weeks of stopping. However, this cannot be extrapolated to the higher doses and longer durations used recreationally, where the depth and reversibility of axis suppression are not established. Recovery should not be assumed. Any post-use recovery strategy must be individualized and directed by an endocrinologist with baseline and follow-up hormone testing; do not self-manage suppression. This monograph does not endorse any SERM or hormonal 'recovery' protocol — that is a clinical decision for a physician.

Bloodwork & vitals

Monitoring

Recommended labs & checks
Liver function panel (ALT, AST, ALP, total and direct bilirubin, GGT) at baseline and periodicallyFasting lipid panel (HDL, LDL, triglycerides, total cholesterol)Total and free testosterone, LH, FSH, SHBGComplete blood count including hemoglobin/hematocritPSA in older males at baselineRenal function/creatinine (and CK if muscle pain/dark urine to assess rhabdomyolysis)

Cadence: Baseline before any use; recheck liver enzymes and lipids within 3-4 weeks and at least monthly during use; hormonal axis at baseline, during use, and after cessation to document suppression and recovery. Any use should be under a clinician's supervision.

Warning signs — seek care
  • Jaundice (yellowing of skin/eyes), dark urine, pale stools
  • Right-upper-quadrant or abdominal pain, nausea, persistent fatigue, unexplained itching (pruritus)
  • Unexplained weight loss or loss of appetite
  • Chest pain, shortness of breath, leg swelling or signs of clot
  • Severe muscle pain, weakness, or cola-colored urine (possible rhabdomyolysis)
  • Loss of libido, testicular shrinkage, mood disturbance
Do not use if

Contraindications

  • Not approved for human use for any indication; use is off-label and experimental
  • Pre-existing liver disease or elevated baseline liver enzymes
  • Pregnancy and breastfeeding (androgenic/teratogenic potential; no human safety data)
  • History of, or high risk for, cardiovascular disease or dyslipidemia (HDL-lowering effect)
  • Concurrent hepatotoxic drugs, heavy alcohol use, or other anabolic agents/SARMs/steroids (additive liver and endocrine risk)
  • Personal or family history of hormone-sensitive concerns without physician oversight
  • Adolescents/individuals who are not skeletally or hormonally mature
Combinations

Interaction profile

  • ModerateWith a thermogenic stimulant: Additive cardiovascular strain
  • ModerateWith an anabolic steroid: Hormonal
  • ContraindicatedWith DNP: Additive cardiovascular strain

Check a specific combination in the interaction checker.

Harm reduction

Reducing harm & when to stop

  • The safest option is not to use LGD-4033; it is an unapproved, experimental drug with no established long-term human safety data at the doses people actually take.
  • Do not treat SARMs as a 'safe steroid alternative' — documented harms include serious liver injury and testosterone-axis shutdown.
  • If using despite the risks, do so only with physician involvement and get baseline bloodwork (liver panel, lipids, full hormone panel, CBC) before starting and repeat during use.
  • Stop immediately and seek urgent medical care for any sign of liver injury: jaundice, dark urine, pale stools, right-upper-quadrant pain, severe fatigue, or unexplained itching.
  • Seek care for chest pain, breathlessness, leg swelling (possible clot), or severe muscle pain with dark urine (possible rhabdomyolysis).
  • Avoid combining with alcohol, other hepatotoxic drugs, or any other SARMs/anabolic steroids, which compound liver and endocrine risk.
  • Assume products are mislabeled or contaminated; actual contents and dose are unreliable.
  • Do not attempt to self-manage suppressed testosterone; recovery and any hormonal management must be directed by an endocrinologist.
  • Keep total exposure (dose and duration) as low as possible and involve a clinician throughout; discontinue at the first adverse sign.
Evidence

Citations (12)

Every clinical claim above is tied to a primary source. Overall evidence grade C — graded to the best available evidence for its core claims.

  1. 01

    LGD-4033 is a non-steroidal oral SARM that binds the androgen receptor with high affinity and selectivity, with a tissue-selective anabolic profile; rationale is muscle/bone activity with relatively lower prostate activity.

    RCTThe safety, pharmacokinetics, and effects of LGD-4033, a novel nonsteroidal oral, selective androgen receptor modulator, in healthy young men.PMID 22459616 ↗

  2. 02

    In a placebo-controlled RCT of 76 healthy young men given 0.1, 0.3, or 1.0 mg/day for 21 days, LGD-4033 dose-dependently increased lean body mass without significant change in fat mass.

    RCTThe safety, pharmacokinetics, and effects of LGD-4033, a novel nonsteroidal oral, selective androgen receptor modulator, in healthy young men.PMID 22459616 ↗

  3. 03

    LGD-4033 dose-dependently suppressed total testosterone, SHBG, HDL cholesterol and triglycerides; free testosterone and FSH were significantly suppressed only at the 1.0 mg dose; hormones and lipids returned toward baseline after discontinuation.

    RCTThe safety, pharmacokinetics, and effects of LGD-4033, a novel nonsteroidal oral, selective androgen receptor modulator, in healthy young men.PMID 22459616 ↗

  4. 04

    LGD-4033 had a long elimination half-life with dose-proportional accumulation on multiple dosing; PSA, hemoglobin, AST, ALT and QT interval did not change significantly at the doses/duration studied.

    RCTThe safety, pharmacokinetics, and effects of LGD-4033... in healthy young men.DOI 10.1093/gerona/gls078 ↗

  5. 05

    Ligandrol (LGD-4033) caused severe drug-induced liver injury; liver biopsy showed cholestatic hepatitis with mild portal, periportal and perisinusoidal fibrosis in a 32-year-old man.

    Case reportLigandrol (LGD-4033)-Induced Liver Injury.PMID 32637435 ↗

  6. 06

    High-dose LGD-4033 use (~3 months) caused drug-induced liver injury presenting with pruritic jaundice, weight loss and elevated liver enzymes in a 52-year-old man after exclusion of other causes.

    Case reportLGD-4033 and a Case of Drug-Induced Liver Injury: Exploring the Clinical Implications of Off-Label Selective Androgen Receptor Modulator Use in Healthy Adults.PMID 39421081 ↗

  7. 07

    Off-label LGD-4033 use in healthy adults is associated with hepatotoxicity, cardiovascular complications, endocrine disturbances and psychiatric symptoms, and it is not a safe alternative to anabolic steroids.

    Case reportLGD-4033 and a Case of Drug-Induced Liver Injury: Exploring the Clinical Implications of Off-Label SARM Use in Healthy Adults.DOI 10.7759/cureus.69601 ↗

  8. 08

    Co-administration of LGD-4033 (10 mg/day) with MK-677 for 5 weeks increased body, lean and fat mass while lowering HDL (~36%) and raising LDL/triglycerides, elevating AST/ALT, and suppressing total/free testosterone, SHBG and FSH; most values returned to baseline post-cycle.

    Case reportLGD-4033 and MK-677 use impacts body composition, circulating biomarkers, and skeletal muscle androgenic hormone and receptor content: A case report.PMID 36303408 ↗

  9. 09

    Systematic review of SARM safety in healthy adults found recurring case reports of drug-induced liver injury, plus reports of tendon rupture and rhabdomyolysis, and commonly reported ALT elevations in SARM-exposed trial participants.

    ReviewSystematic Review of Safety of Selective Androgen Receptor Modulators in Healthy Adults: Implications for Recreational Users.PMID 37218811 ↗

  10. 10

    SARMs including ligandrol are increasingly misused as purportedly 'safe' steroid alternatives; long-term use can carry serious clinical consequences including liver damage, myocardial infarction and blood clots.

    Case seriesPerspectives in Evaluating Selective Androgen Receptor Modulators in Human Hair: A Short Communication.PMID 33337588 ↗

  11. 11

    LGD-4033 is extensively metabolized to multiple phase I metabolites excreted in urine, with long detection windows relevant to clearance/washout.

    PreclinicalInvestigations into the elimination profiles and metabolite ratios of micro-dosed selective androgen receptor modulator LGD-4033 for doping control purposes.PMID 34734312 ↗

  12. 12

    Commercial products sold as SARMs, including ligandrol, are frequently mislabeled or contaminated and may contain other SARMs, steroids or growth-hormone secretagogues.

    PreclinicalVariation of Sequential Ligandrol (LGD-4033) Metabolite Levels in Routine Anti-Doping Urine Samples Detected with or without Other Xenobiotics.PMID 37764261 ↗

Last reviewed 2026-07-06 · Verified against PubMed · Educational, not medical advice