LGD-4033 (Ligandrol): Phase I Study, State of Evidence and Risk Profile

LGD-4033, also known as Ligandrol, stands out among SARMs for one reason: a phase I study in healthy men has been published. That is unusual in this category and warrants a separate discussion, because it provides more evidence than is available for compounds supported only by animal models and case reports.

This distinction is often overinterpreted. A phase I study addresses short-term safety and pharmacokinetics, not efficacy or safety during prolonged exposure. This article explains what the study establishes and where its limits lie. It does not provide doses or protocols for use.

All substances discussed in this article are research compounds and are not intended for human consumption. Their effects are described solely on the basis of laboratory studies and experimental observations, not clinical recommendations.

What is LGD-4033?

LGD-4033 is an orally active, non-steroidal selective androgen receptor modulator. Like RAD-140, it lacks a steroidal scaffold even though it interacts with the same receptor as testosterone.

The SARM class as a whole, including classification criteria, shared mechanisms and compounds incorrectly placed in this group, is discussed in our overview of SARMs as a group. This article focuses solely on Ligandrol.

Phase I study: what was actually shown

In 2013, researchers published a study evaluating the safety, pharmacokinetics and effects of LGD-4033 in healthy young men (Basaria et al., 2013, PMID 22459616). It remains the only study of its kind for this compound and one of the few across the category.

What the study establishes

A phase I study can answer questions about short-term tolerability, pharmacokinetics and changes in selected parameters during a limited exposure period in a small group of participants.

What it does not establish

• It does not establish efficacy for any indication. That requires phase II and phase III trials, which were not completed for LGD-4033.
• It does not establish long-term safety. By definition, the observation period in this type of study is short.
• It does not reflect uncontrolled real-world exposure, including exposure levels and durations outside the study or combinations with other substances.

The LGD-4033 clinical development program did not result in registration. The compound is not authorized as a medicinal product in the European Union or the United States.

A systematic review provides a broader picture of SARM safety in healthy adults and the implications for recreational users (Vignali et al., 2023, PMID 37218811). A separate systematic review examines SARM use by athletes (Vasireddi et al., 2025, PMID 39755947).

Reported cases of liver injury

Most case reports involving Ligandrol concern liver injury. They should be read alongside the phase I findings because they illustrate the difference between controlled study conditions and uncontrolled real-world exposure.

• A case of Ligandrol-associated drug-induced liver injury was published in the ACG Case Reports Journal (Barbara et al., 2020, PMID 32637435).
• Another case was reported in the German medical literature (Wallstab et al., 2023, PMID 36257328).
• A 2024 report described liver injury in a healthy adult and discussed the consequences of off-label SARM use (Labban et al., 2024, PMID 39421081). A further case was published in the same year (Demangone et al., 2024, PMID 39328701).
• A case report and literature review provides broader context on liver injury after SARM exposure (Mertens et al., 2024, PMID 37871633).

Methodological note: case reports cannot estimate how frequently an event occurs. They show that an event occurred and was associated with a reported exposure. Repeated observations from independent centers nevertheless represent a signal that should not be ignored.

Concurrent use of LGD-4033 and MK-677

A case report documented changes in body composition, circulating markers and androgen receptor content in skeletal muscle during concurrent use of LGD-4033 and MK-677 (Cardaci et al., 2022, PMID 36303408). This is a single case, not a controlled trial. It is included because combinations of compounds are commonly reported outside research settings.

Regulatory status

LGD-4033 is not registered as a medicinal product in the European Union or the United States. It is not a dietary supplement, food or cosmetic and is not eligible for authorized health claims. Regulatory authorities have warned about products containing SARMs that are marketed as sports supplements.

Anti-doping note

LGD-4033 falls within category S1.2 of the WADA Prohibited List: other anabolic agents, including selective androgen receptor modulators. It is prohibited at all times, both in and out of competition.

Ligandrol is one of the most extensively characterized compounds in this group from an analytical perspective. Its metabolism in humans has been described (Fragkaki et al., 2018, PMID 30255601), and a team from the Polish anti-doping laboratory analyzed variation in metabolite concentrations in routine samples (Kwiatkowska et al., 2023, PMID 37764261).

Of particular relevance is a study of elimination profiles after administration of very small amounts of the compound for doping-control purposes (Wagener et al., 2022, PMID 34734312). The practical implication is that detection does not require substantial exposure. General analytical methods for detecting SARMs are also well described (Thevis and Schänzer, 2018, PMID 28137616).

In Poland, the rules are administered by the Polish Anti-Doping Agency (POLADA), and amateur athletes participating in covered competitions may also be tested. Because LGD-4033 is not a registered medicine, there is no basis for a Therapeutic Use Exemption for this compound.

What is actually in the product?

An analysis published in JAMA examined 44 products sold online as SARMs. Only 52% contained any SARM, 39% contained another unapproved drug, and only 41% contained an amount consistent with the label (Van Wagoner et al., 2017, PMID 29183075). A newer European study examined products of suspected illegal origin for SARMs, metabolic modulators and growth hormone secretagogues (Barrios et al., 2025, PMID 40551438).

Taken together with the elimination data at very low exposure, these findings have an important implication for athletes: an anti-doping violation may result from product contamination, and detection does not require deliberate use of a substantial amount. Material identity must be assessed through batch-specific analytical documentation.

Harm reduction

• A phase I study is not evidence of long-term safety. It addresses short-term tolerability in a small group under controlled conditions.
• Multiple cases of liver injury have been reported for this compound. Yellowing of the skin or sclera, dark urine, nausea and weakness require urgent medical assessment.
• Suppression of the hypothalamic-pituitary-gonadal axis is relevant to the SARM class as a whole and is discussed in the parent article.
• Combining substances multiplies the unknowns. A poisoning case following concurrent exposure to two compounds in this area has been reported (Kintz et al., 2021, PMID 34678947).

Frequently Asked Questions

Is LGD-4033 tested in humans?

A phase I study in healthy young men has been published (PMID 22459616), which is unusual in this category. It addresses short-term tolerability and pharmacokinetics, not efficacy or safety during prolonged exposure. The clinical development program did not result in registration of LGD-4033.

Does completing phase I mean it is safe?

No. A phase I study covers a short period, a small group and controlled conditions. Several independent reports of drug-induced liver injury after Ligandrol have also been published under real-world conditions that differ from the trial setting.

Does non-steroidal structure mean no liver burden?

No. The absence of a steroidal scaffold and 17-alpha alkylation does not establish an absence of hepatotoxicity, as the cited case reports demonstrate.

Is ligandrol detectable at low exposure?

Yes. Elimination profiles after very small amounts have been studied for doping-control purposes (PMID 34734312). Combined with the risk of product contamination, this means that a rule violation may occur without deliberate exposure.

Why does the article not give doses?

Because LGD-4033 is not a medicinal product and has not completed the registration process through which an authorized dosage would be established.

Summary

LGD-4033, or Ligandrol, is a non-steroidal selective androgen receptor modulator distinguished by a published phase I study in healthy young men. That study addresses short-term tolerability and pharmacokinetics, not efficacy or safety during prolonged exposure, and the clinical development program did not result in registration in either the European Union or the United States. Multiple independent case reports have described drug-induced liver injury after real-world exposure. LGD-4033 is also one of the best analytically characterized compounds in its group: human metabolism has been studied, and elimination profiles after very small amounts show that anti-doping detection does not require substantial exposure. Together with documented discrepancies between product labels and contents, this creates a risk of a rule violation without deliberate use. LGD-4033 falls within WADA category S1.2 and is prohibited at all times, with no basis for a Therapeutic Use Exemption for this compound.

Product documentation

Research material pages with batch-specific analytical documentation are available for the capsule form and the 30 ml solution. The complete range is listed under SARMs and modulators. These materials are intended for research purposes only.

Bibliography

1. 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. J Gerontol A Biol Sci Med Sci. 2013;68(1):87–95. PMID: 22459616
2. Barbara M, Dhingra S, Mindikoglu AL. Ligandrol (LGD-4033)-Induced Liver Injury. ACG Case Rep J. 2020;7(6):e00370. PMID: 32637435
3. Wallstab F, Jechorek D, Keitel-Anselmino V, von Arnim U. [Ligandrol-induced liver injury — Case Report]. Z Gastroenterol. 2023;61(5):522–525. PMID: 36257328
4. Labban H, Kwait B, Paracha A, Islam M, Kim DO. LGD-4033 and a Case of Drug-Induced Liver Injury: Exploring the Clinical Implications of Off-Label Selective Androgen Receptor Modulator Use in Healthy Adults. Cureus. 2024;16(9):e69601. PMID: 39421081
5. Demangone MR, Abi Karam KR, Li J. Selective Androgen Receptor Modulators Leading to Liver Injury: A Case Report. Cureus. 2024;16(8):e67958. PMID: 39328701
6. Mertens JE, Bommer MTC, Regier MB, et al. Liver Injury after Selective Androgen Receptor Modulator Intake: A Case Report and Review of the Literature. Z Gastroenterol. 2024;62(6):935–943. PMID: 37871633
7. Cardaci TD, Machek SB, Wilburn DT, et al. LGD-4033 and MK-677 use impacts body composition, circulating biomarkers, and skeletal muscle androgenic hormone and receptor content: A case report. Exp Physiol. 2022;107(12):1467–1476. PMID: 36303408
8. Fragkaki AG, Sakellariou P, Kiousi P, et al. Human in vivo metabolism study of LGD-4033. Drug Test Anal. 2018;10(11–12):1635–1645. PMID: 30255601
9. Kwiatkowska D, Wicka M, Grucza K, Konarski P, Drapała A, Kaliszewski P. Variation of Sequential Ligandrol (LGD-4033) Metabolite Levels in Routine Anti-Doping Urine Samples Detected with or without Other Xenobiotics. Molecules. 2023;28(18):6486. PMID: 37764261
10. Wagener F, Guddat S, Görgens C, et al. Investigations into the elimination profiles and metabolite ratios of micro-dosed selective androgen receptor modulator LGD-4033 for doping control purposes. Anal Bioanal Chem. 2022;414(2):1151–1162. PMID: 34734312
11. Vignali JD, Pak KC, Beverley HR, et al. Systematic Review of Safety of Selective Androgen Receptor Modulators in Healthy Adults. J Xenobiot. 2023;13(2):218–236. PMID: 37218811
12. Vasireddi N, Hahamyan HA, Gould HP, et al. Athlete Selective Androgen Receptor Modulators Abuse: A Systematic Review. Am J Sports Med. 2025;53(4):999–1009. PMID: 39755947
13. Thevis M, Schänzer W. Detection of SARMs in doping control analysis. Mol Cell Endocrinol. 2018;464:34–45. PMID: 28137616
14. Van Wagoner RM, Eichner A, Bhasin S, Deuster PA, Eichner D. Chemical Composition and Labeling of Substances Marketed as Selective Androgen Receptor Modulators and Sold via the Internet. JAMA. 2017;318(20):2004–2010. PMID: 29183075
15. Barrios MM, Deconinck E, Vanhee C, et al. SARMs, Metabolic Modulators and Growth Hormone Secretagogues in Suspected Illegal Medicines, Bought as Sport Performance Enhancers. Drug Test Anal. 2025;17(10):2078–2085. PMID: 40551438
16. Kintz P, Gheddar L, Paradis C, et al. Peroxisome Proliferator-Activated Receptor Delta Agonist (PPAR-delta) and Selective Androgen Receptor Modulator (SARM) Abuse. Toxics. 2021;9(10):251. PMID: 34678947