S-4 (Andarine): The Selective SARM for Lean Muscle, Strength, and Bone Research

Introduction

S-4, also known as Andarine, is one of the earliest and most widely studied Selective Androgen Receptor Modulators (SARMs). Originally developed by GTx, Inc., S-4 was designed as a tissue-selective androgen receptor agonist, intended to help treat muscle wasting, osteoporosis, and benign prostatic hyperplasia (BPH)—without the unwanted effects of traditional steroids or testosterone therapy.

Despite being surpassed in popularity by more recent SARMs like RAD-140 and LGD-4033, S-4 remains a staple compound in muscle and bone research, especially for those seeking to model:

• Lean mass preservation
  
• Strength enhancement
  
• Bone mineral density support
  
• Selective androgenic activity
  

In this blog, we’ll explore the science behind S-4, how it works, what early studies found, how it compares to other SARMs and anabolic agents, and what makes it unique in the SARM family.

What Is S-4 (Andarine)?

S-4 is a non-steroidal SARM developed to bind selectively to androgen receptors (ARs) in muscle and bone. Its anabolic properties help preserve and build lean tissue while its selectivity reduces the risk of androgenic side effects, such as prostate enlargement, hair loss, or liver toxicity.

Key Features:

• Orally bioavailable
  
• Moderate anabolic potency
  
• No aromatization to estrogen
  
• Initially developed to treat BPH and osteoporosis
  
• Offers mild testosterone suppression in animal studies
  

Although newer SARMs are more potent, S-4 is known for its balance of efficacy, safety, and tolerability in preclinical models.

How Does S-4 Work?

S-4 works by binding to the androgen receptor (AR), the same receptor activated by testosterone and DHT. Once bound, S-4 selectively stimulates anabolic activity in muscle and bone tissues, but with reduced activity in reproductive tissues such as the prostate.

Mechanism of Action:

1. Binds to androgen receptors in skeletal muscle and bone.
   
2. Triggers anabolic gene expression that increases protein synthesis.
   
3. Stimulates bone-building osteoblasts, helping improve bone strength.
   
4. Does not convert to estrogen or DHT, avoiding hormonal imbalances common with steroids.
   

This tissue-selective behavior makes S-4 valuable for researchers studying androgen-related pathways without the systemic burden of synthetic hormones.

Preclinical and Early Research

1. Muscle Preservation and Growth

In one of the first studies published by GTx, S-4:

• Increased lean body mass in animal models
  
• Prevented muscle loss during caloric restriction
  
• Demonstrated partial agonist activity, meaning it acts like testosterone in muscle but more weakly in reproductive tissue
  

S-4 became one of the first SARMs evaluated for sarcopenia and cachexia modeling in rats.

2. Bone Health and Density

S-4 has been studied for:

• Improving bone mineral density (BMD)
  
• Supporting bone strength and microarchitecture
  
• Preventing osteoclast activity (bone resorption)
  

These effects make it ideal for preclinical research in osteopenia, postmenopausal bone loss, or age-related skeletal degeneration.

3. Prostate Research

Originally, S-4 was investigated for benign prostatic hyperplasia (BPH):

• It inhibited prostate growth in rats
  
• Delivered anabolic effects without prostate enlargement
  
• Suggested potential as a partial antagonist in reproductive tissue
  

This selectivity for muscle and bone over the prostate was a key motivation behind SARMs as a therapeutic category.

S-4 Compared to Other SARMs

S-4 offers a balance between muscle-building efficacy and a relatively mild suppression profile, making it suitable for conservative or long-duration research protocols.

Research Applications of S-4

S-4 is used in a variety of preclinical studies, including:

1. Sarcopenia and Aging

• Models age-related muscle loss
  
• Useful for studying testosterone alternatives in elderly populations
  

2. Caloric Restriction & Fat Loss

• Preserves lean mass while reducing body fat
  
• Great for cutting-phase body composition research
  

3. Bone Density Research

• Explores androgen effects on bone strength without estrogen
  
• Ideal for osteoporosis and postmenopausal studies
  

4. Post-Injury Recovery

• Helps prevent muscle loss during immobilization or surgical recovery in lab models
  

5. Strength & Endurance Models

• S-4 improves muscle density and hardness, not just size
  
• Useful in athletic performance simulations
  

Potential Side Effects in Research

While S-4 is generally well-tolerated, it has a unique side effect profile researchers should be aware of.

Known and Reported Effects:

The vision-related side effects appear to be unique to S-4 and occur when the compound interacts with receptors in the retina. This side effect typically resolves upon cessation and is dose-dependent, often appearing at doses above 50 mg/day in anecdotal reports.

Legal and Regulatory Status

As of 2025, S-4 is:

• Not approved by the FDA for human use
  
• Classified as a research chemical only
  
• Banned by WADA and all major athletic organizations
  
• Illegal to market for human consumption or bodybuilding
  

Required Labeling:

“For research purposes only. Not for human or veterinary use.”

Dosing in Research Models

Note: The following is based on animal and in vitro data—not medical advice.

Common Preclinical Parameters:

• Dosage Range: 25–75 mg/day (scaled for animal models)
  
• Cycle Duration: 4–8 weeks for lean mass, up to 12 weeks for bone density
  
• Delivery: Oral administration
  

Due to vision side effects, researchers often experiment with lower doses or alternate-day protocols in sensitive animal models.

Stacking S-4 in Research Protocols

S-4 is often used in cutting and strength-focused studies, sometimes stacked with other agents for recomposition modeling.

Stacks must be carefully controlled to monitor overlapping suppression or compound-specific side effects.

S-4 vs. Anabolic Steroids

S-4 provides a cleaner, drier anabolic profile than many anabolic steroids, with lower systemic burden—but the vision effects are a unique tradeoff.

Summary Table

Final Thoughts

S-4 (Andarine) remains a foundational compound in SARM research, offering a moderate yet consistent anabolic effect with muscle and bone selectivity. It’s particularly useful in studies involving:

• Muscle preservation during dieting or inactivity
  
• Strength enhancement without bloating
  
• Bone density improvement in androgen-deficient models
  
• Potential suppression studies or post-cycle recovery evaluation
  

Its tissue selectivity, oral delivery, and mild suppression profile make it a versatile tool for labs and researchers exploring androgen biology. While newer SARMs offer more power, S-4 offers reliability and consistency—especially when the goal is to study androgenic effects without overwhelming systemic impact.

Disclaimer: S-4 is a research chemical not approved for human use. This blog post is for educational purposes only and does not constitute medical advice. Always follow all local, national, and international laws when researching, handling, or distributing S-4 or any investigational compounds.

References

1. Dalton, J.T., et al. (2003). “Selective Androgen Receptor Modulators in Preclinical Development.” Current Opinion in Investigational Drugs.
   
2. Gao, W., et al. (2005). “S-4, a novel SARM: potent anabolic activity with reduced prostate growth.” Endocrinology.
   
3. Kearbey, J.D., et al. (2007). “Tissue-selective anabolic effects of Andarine in castrated rats.” Journal of Pharmacology and Experimental Therapeutics.
   
4. GTx, Inc. Development Briefings on S-4.
   
5. WADA Prohibited List (2025). World Anti-Doping Agency.