---
title: "LGD-4033 (Ligandrol)"
slug: "lgd-4033"
type: "compound"
category: "Body Composition"
url: "https://peptidesciencethailand.com/compounds/lgd-4033"
description: "A selective androgen receptor modulator studied for lean mass and bone density in clinical settings. Research evidence, mechanism, and safety considerations."
---
# LGD-4033 (Ligandrol)

*Selective Androgen Receptor Modulator, Targeting Muscle and Bone with Tissue Selectivity*

**Category:** Body Composition  
**Format:** Lyophilized Vial  
**Amount:** 10mg  
**Purity:** >99% (HPLC)

## Overview

LGD-4033, also known as Ligandrol or VK5211, is a non-steroidal selective androgen receptor modulator (SARM) originally developed by Ligand Pharmaceuticals and subsequently licensed to Viking Therapeutics for clinical development. With the molecular formula C14H12F6N2O and a molecular weight of 338.25 g/mol, LGD-4033 is a small synthetic molecule that binds to androgen receptors with high affinity and selectivity. It is classified as a SARM, not a peptide, anabolic steroid, or prohormone, and represents a distinct class of investigational compounds designed to exert tissue-selective androgenic effects.

The fundamental principle underlying SARM development is tissue selectivity. Traditional anabolic-androgenic steroids (AAS) activate androgen receptors uniformly throughout the body, producing both desired anabolic effects in muscle and bone and undesired androgenic effects in the prostate, skin, and other tissues. SARMs like LGD-4033 were designed to preferentially activate androgen receptors in skeletal muscle and bone tissue while demonstrating reduced activity in androgenic tissues. This selectivity is achieved through the compound's unique conformational influence on the androgen receptor (AR), which triggers tissue-specific co-regulator recruitment upon binding.

When LGD-4033 binds to the androgen receptor, it induces a conformational change in the receptor's ligand-binding domain that differs subtly from the conformation produced by testosterone or dihydrotestosterone. This altered conformation affects which co-activator and co-repressor proteins are recruited to the receptor-DNA complex, ultimately determining which genes are transcribed in response to receptor activation. In muscle tissue, the LGD-4033-AR complex preferentially recruits anabolic co-activators that drive myofibrillar protein synthesis, satellite cell proliferation, and muscle fiber hypertrophy. In prostate tissue, the same compound-receptor complex recruits a different set of co-regulators that produce a muted androgenic response.

Clinical research on LGD-4033 has produced notable results. A Phase I dose-escalation trial published in the Journal of Gerontology: Medical Sciences demonstrated that healthy young men receiving 1mg of LGD-4033 daily for 21 days experienced statistically significant increases in lean body mass (average 1.21 kg increase) compared to placebo. This study, conducted at the Boston University Medical Center, also confirmed dose-dependent pharmacokinetics and established the compound's safety profile at multiple dose levels (0.1mg, 0.3mg, and 1.0mg daily).

The anabolic mechanism of LGD-4033 in skeletal muscle involves several interconnected molecular pathways. Upon AR activation in myocytes, the compound stimulates the mTOR (mechanistic target of rapamycin) signaling pathway, a master regulator of muscle protein synthesis. mTOR pathway activation increases the phosphorylation of downstream targets including p70S6K and 4E-BP1, which enhance ribosomal biogenesis and translational capacity, enabling greater rates of contractile protein production. Concurrently, LGD-4033 appears to suppress myostatin signaling, a negative regulator of muscle growth, further shifting the balance toward net protein accretion.

In bone tissue, LGD-4033 activates androgen receptors in osteoblasts, the cells responsible for bone formation. This activation stimulates osteoblast differentiation and mineralization activity while modulating the RANK/RANKL/OPG pathway that regulates osteoclast-mediated bone resorption. Preclinical studies have demonstrated dose-dependent increases in bone mineral density and cortical bone strength in animal models, suggesting potential relevance for research into conditions characterized by skeletal fragility.

The pharmacokinetic profile of LGD-4033 is characterized by high oral bioavailability (approximately 100%), a long elimination half-life of 24-36 hours, and linear dose-proportional pharmacokinetics. These properties allow for convenient once-daily oral dosing and produce stable steady-state plasma concentrations within 7-14 days of continuous administration. The compound is primarily metabolized by hepatic CYP3A4 enzymes, which is relevant for potential drug interactions.

An important consideration in LGD-4033 research is its dose-dependent suppression of endogenous testosterone production. Clinical data have shown that LGD-4033 suppresses serum testosterone and sex hormone-binding globulin (SHBG) levels in a dose-dependent manner through negative feedback on the hypothalamic-pituitary-gonadal (HPG) axis. In the Phase I trial, the 1mg dose produced a 50% reduction in total testosterone by day 21, although levels returned toward baseline during the post-treatment recovery period. This HPG axis suppression is a critical consideration for research protocol design and underscores the importance of specialist oversight.

LGD-4033 does not undergo aromatization to estrogen and does not interact with the estrogen receptor, meaning it does not produce estrogenic side effects such as gynecomastia or water retention. Similarly, it does not undergo 5-alpha reduction to a more potent androgen, which contributes to its reduced androgenic activity in tissues like the prostate and skin where 5-alpha-reductase is highly expressed. These pharmacological properties distinguish LGD-4033 from traditional anabolic steroids and contribute to its improved side effect profile in preclinical and early clinical research.

Research continues to explore LGD-4033's potential applications in conditions characterized by muscle wasting and bone loss. Viking Therapeutics has advanced the compound (as VK5211) into Phase II clinical trials for hip fracture recovery, with preliminary results suggesting improvements in lean mass and functional performance. These ongoing studies represent important progress in understanding the clinical potential of tissue-selective androgen receptor modulation.

## Mechanism of Action

### Step 1: Selective Androgen Receptor Binding

LGD-4033 binds to the androgen receptor ligand-binding domain with high affinity, inducing a conformational change that differs from testosterone binding and triggers tissue-specific co-regulator recruitment patterns.

### Step 2: Tissue-Specific Co-Regulator Recruitment

In muscle and bone, the LGD-4033-AR complex recruits anabolic co-activator proteins that drive pro-growth gene transcription. In androgenic tissues (prostate, skin), different co-regulators are engaged, producing a muted response.

### Step 3: mTOR Pathway Activation in Muscle

AR activation in myocytes stimulates the mTOR signaling cascade, phosphorylating p70S6K and 4E-BP1 to enhance ribosomal activity and translational capacity, driving increased rates of myofibrillar protein synthesis.

### Step 4: Osteoblast Stimulation in Bone

In bone tissue, LGD-4033 activates osteoblast differentiation and mineralization via AR-mediated transcription, while modulating the RANK/RANKL/OPG axis to reduce osteoclast-mediated bone resorption.

### Step 5: Lean Mass Accretion and Composition Shift

The combined effects of increased protein synthesis, reduced myostatin signaling, and enhanced bone formation produce measurable increases in lean body mass and bone mineral density, shifting overall body composition toward a more anabolic state.

## Researched Benefits

### Lean Mass Accretion

A Phase I clinical trial demonstrated that 1mg/day of LGD-4033 for 21 days produced a statistically significant average increase of 1.21 kg in lean body mass in healthy young men. This anabolic effect is mediated through AR-dependent stimulation of mTOR-driven protein synthesis in skeletal muscle.

### Tissue-Selective Androgen Activity

LGD-4033 demonstrates a high ratio of anabolic to androgenic activity, producing robust effects in muscle and bone while exhibiting reduced activity in prostate and skin tissues. This selectivity results from tissue-specific co-regulator recruitment rather than differential receptor binding.

### Bone Mineral Density Support

Preclinical studies show dose-dependent increases in bone mineral density and cortical bone strength with LGD-4033 treatment. The compound stimulates osteoblast activity and modulates the bone remodeling balance toward net bone formation, with clinical trials ongoing for hip fracture recovery.

### Oral Bioavailability and Convenience

LGD-4033 demonstrates nearly 100% oral bioavailability with a 24-36 hour half-life, allowing once-daily oral dosing. This pharmacokinetic profile produces stable plasma concentrations and eliminates the need for injections, simplifying research protocol administration.

## Dosage & Administration

| Parameter | Detail |
| --- | --- |
| Protocol | 1-10mg per day, administered orally once daily |
| Route | Oral administration |
| Duration | 6-8 week cycles |
| Cycle Notes | Research protocols typically use 5-10mg daily for 6-8 weeks. Due to dose-dependent HPG axis suppression, a post-cycle recovery period is standard. The 1mg dose used in the Phase I trial produced significant lean mass gains, suggesting lower doses may be sufficient for many applications. |
| Reconstitution | For research-grade lyophilized formulations, reconstitute with appropriate solvent per protocol specifications. LGD-4033 is commonly prepared in oral solution or capsule form for research use. |

> **Specialist note:** A your specialist will assess hormonal status (testosterone, LH, FSH, SHBG), liver function, lipid panels, and metabolic markers before initiating LGD-4033 research. Post-cycle hormonal monitoring is essential due to dose-dependent suppression of the HPG axis. Individuals with hepatic impairment or those taking CYP3A4-metabolized medications require adjusted protocols.

## Compound Reference Data

| Property | Value |
| --- | --- |
| Format | Lyophilized Powder |
| Amount | 10mg per vial |
| Purity | >99% |
| Purity Method | HPLC (High-Performance Liquid Chromatography) |
| Composition | LGD-4033 (Ligandrol/VK5211), non-steroidal SARM |
| Molecular Weight | 338.25 g/mol |
| Storage | Store at room temperature (15-25°C) in a dry, light-protected environment. |
| Appearance | White crystalline powder |

## Medical Guidance

LGD-4033 produces dose-dependent suppression of the hypothalamic-pituitary-gonadal axis, reducing endogenous testosterone and SHBG levels. This hormonal suppression is reversible but requires careful monitoring and post-cycle management. Individuals with pre-existing hormonal disorders, liver disease, cardiovascular conditions, or those taking hormonal medications or CYP3A4 inhibitors/inducers must undergo comprehensive medical assessment. LGD-4033 is prohibited in competitive athletics by the World Anti-Doping Agency (WADA).

## Frequently Asked Questions

### What is LGD-4033 and is it a steroid?

LGD-4033 (Ligandrol) is a non-steroidal selective androgen receptor modulator (SARM). It is not an anabolic steroid, peptide, or prohormone. SARMs are a distinct class of synthetic compounds designed to selectively activate androgen receptors in muscle and bone tissue while reducing activation in other tissues. LGD-4033 achieves this selectivity through tissue-specific co-regulator recruitment upon receptor binding.

### Does LGD-4033 suppress testosterone?

Yes. Clinical data demonstrate that LGD-4033 produces dose-dependent suppression of serum testosterone and SHBG through negative feedback on the HPG axis. At 1mg/day for 21 days, approximately 50% testosterone suppression was observed. However, this suppression is reversible, with levels trending toward baseline recovery after cessation. Post-cycle monitoring and recovery protocols are standard in research.

### How does LGD-4033 differ from traditional anabolic steroids?

LGD-4033 differs from steroids in several important ways: it does not aromatize to estrogen (no estrogenic side effects), does not undergo 5-alpha reduction (reduced androgenic effects in prostate and skin), demonstrates tissue-selective androgen receptor activation, and is orally bioavailable without liver toxicity associated with 17-alpha alkylated oral steroids. However, it does share the property of HPG axis suppression with traditional androgens.

### What clinical trials have been conducted on LGD-4033?

A Phase I dose-escalation trial at Boston University demonstrated safety, tolerability, and significant lean mass increases at doses of 0.1mg to 1.0mg daily. Viking Therapeutics (under the name VK5211) has advanced into Phase II trials for hip fracture recovery, with preliminary results showing improvements in lean mass and functional endpoints. These represent the most advanced clinical data available for any SARM compound.

### Is LGD-4033 prohibited in competitive sports?

Yes. LGD-4033 is classified as a prohibited substance by the World Anti-Doping Agency (WADA) under the category S1.2 (Other Anabolic Agents). It is also banned by most professional and amateur athletic organizations. Multiple athletes have received sanctions for positive LGD-4033 tests. This compound is intended exclusively for supervised research under specialist guidance.

## Related Compounds

- /compounds/mk-677
- /compounds/tesamorelin
- /compounds/aod-9604