As humans, we’re always looking for a competitive advantage. Virtually all living organisms in the world compete with members of their own species. Some individuals are highly competitive and eager to get access to high-quality resources, while others seem to avoid competition all together.

SARMS or selective androgen receptor modulators are highly bioavailable investigational non-steroidal alternatives to anabolic steroids,  made to help mitigate the long-term side effects. We’re going to talk about what SARMS are, the most popular types of SARMS and how they work.

What Are Selective Androgen Receptor Modulators (SARMs)?

Introduction to SARMs

Selective Androgen Receptor Modulators (SARMs) are a class of non-steroidal compounds that selectively bind to androgen receptors in specific tissues—primarily skeletal muscle and bone—to promote anabolic activity while minimizing unwanted effects in tissues like the prostate or skin.

Originally developed as an alternative to anabolic-androgenic steroids (AAS), SARMs aim to mimic the muscle-building benefits of testosterone without the side effects associated with aromatization or 5-alpha reduction (e.g., gynecomastia, hair loss, prostate enlargement) Basaria, 2010.

SARMs Covered in This Series

This guide focuses on the most popular and well-researched SARMs and SARM-like compounds:

• Ostarine [MK-2866], Enobosarm

  Andarine [S-4], GTX-007

  Ligandrol [LGD-4033]

  Testolone [RAD-140], EB0062

  As well, as SARM like compounds

  Cardarine [GW501516] Endurobol

  SARM-like PPARδ agonist often misclassified as a true SARM

While steroidal SARMs have existed since the 1940s, modern non-steroidal SARMs emerged in the 1990s and early 2000s to overcome the limitations of steroidal androgens like testosterone and DHT, both of which are associated with cardiovascular and hepatic toxicity (Basaria, 2010).

SARMs have since been investigated for use in:

• Muscle wasting (cachexia)

• Osteoporosis

• Benign prostatic hyperplasia

• Alzheimer’s disease

• Breast cancer

• Muscular dystrophy

• Erectile dysfunction

• Stress urinary incontinence

Mechanism of Action

Unlike anabolic steroids, which bind indiscriminately across the body, SARMs interact with androgen receptors in a tissue-selective manner. Depending on their structure, they may act as full agonists, partial agonists, or antagonists, modulating co-regulator proteins and transcription factors that influence muscle and bone development.

Key Mechanistic Highlights:

• Non-substrates for aromatase or 5α-reductase (they don’t convert to estrogen or DHT)

• Full agonists in muscle and bone

• Partial agonists in prostate and skin

• Selective gene expression based on AR conformation and tissue location (Dalton et al., 2013)

How SARMs Work in the Body

SARMs induce conformational changes in the androgen receptor, leading to selective recruitment of co-activators and tissue-specific transcription of anabolic genes. This makes them ideal for promoting muscle hypertrophy and bone density while minimizing unwanted effects.

Each SARM-AR complex is slightly different, and tissues like the brain, skin, prostate, and liver express different patterns of ARs, explaining variability in action and side effects.

For example:

• Ostarine (MK-2866) affects lipid metabolism, downregulating leptin and adiponectin expression, and may contribute to weight loss through regulation of hunger and fat mobilization (Narayanan et al., 2008).

SARMs bind to androgen receptors (AR) and initiate tissue-selective gene transcription. Unlike testosterone or DHT, SARMs:

• Do not aromatize to estrogen

• Do not convert to DHT via 5α-reductase

• Exhibit partial agonist activity in androgen-sensitive tissues like the prostate

This selectivity is achieved via unique conformational changes in the AR upon SARM binding, which leads to the recruitment of specific coactivator proteins and transcription of anabolic genes in muscle and bone, while sparing reproductive or skin tissues Dalton et al., 2013.

Key Pharmacological Features

• High oral bioavailability

• Tissue-selective action (muscle > prostate)

• No significant liver toxicity (unlike oral AAS)

• Non-aromatizing (no estrogen conversion)

• No suppression of sperm production when cycled properly

Benefits and Clinical Applications of SARMs

1. Increase in Lean Muscle Mass and Bone Density

SARMs like Ostarine (MK-2866) and Ligandrol (LGD-4033) have demonstrated significant increases in lean muscle mass and bone mineral density, making them ideal candidates for treating sarcopenia and cachexia.

A Phase II clinical trial on Ostarine involving 120 elderly men showed that 3mg/day for 12 weeks led to measurable gains in muscle mass and improved physical function without the side effects seen in steroid users
(Dalton et al., 2011).

LGD-4033 is considered one of the most potent SARMs, demonstrating a >500:1 anabolic to androgenic ratio, with excellent oral bioavailability and selectivity for muscle over prostate tissue Basaria, 2010.

2. Neuroprotective Properties (Alzheimer’s and Age-Related Decline)

RAD-140 (Testolone) has shown neuroprotective effects in preclinical models. In vitro, RAD-140:

• Reduced apoptosis (cell death) in hippocampal neurons

• Activated MAPK/ERK signaling pathways

• Offered protection against oxidative damage

These properties suggest potential use in Alzheimer’s disease and age-related cognitive decline (Jayaram et al., 2014).

3. Potential Use in Cancer Therapy (Metastatic Breast Cancer)

Androgen receptor activation via SARMs has demonstrated antitumor effects in ER+/AR+ breast cancer models. RAD-140 was evaluated in a Phase 1 clinical trial in postmenopausal women with metastatic breast cancer (mBC):

• Doses of 50, 100, and 150 mg/day were tested.

• The most common adverse events were elevated liver enzymes and gastrointestinal symptoms.

• Despite these effects, RAD-140 showed promise in suppressing estrogen-responsive tumor growth by modulating estrogen receptor expression and enhancing tumor suppressor gene activity
  (Gucalp et al., 2020).

4. Weight Loss and Lipid Regulation

Ostarine has shown an effect on lipid metabolism by:

• Reducing leptin and adiponectin mRNA expression

• Improving body composition

• Supporting weight loss via modulation of fat metabolism pathways

This makes it a potential adjunct for metabolic syndrome and obesity management (Narayanan et al., 2008).

SARM-Like Compounds: Cardarine (GW501516)

While not a SARM, Cardarine is a PPARδ agonist often included in SARM stacks due to its:

• Fat-burning properties

• Endurance enhancement

• Mitochondrial biogenesis support

However, GW501516 was discontinued in clinical trials due to carcinogenicity in animal models, raising safety concerns for long-term use (Gonzalez et al., 2009).

Safety and Side Effects of SARMs

Common Side Effects

• Suppression of natural testosterone (dose- and duration-dependent)

• Elevated liver enzymes (in some cases, reversible)

• Headaches, nausea, acne

• Possible mood changes

Mitigation Strategies

• Post-cycle therapy (PCT) with Clomid or Nolvadex

• Liver support supplements

• On-cycle blood work monitoring

SARMs are not approved by the FDA for recreational use or bodybuilding, and their long-term safety profiles are still being researched.

SARMs represent a new frontier in performance enhancement, medical therapy, and anti-aging strategies. With greater selectivity, fewer side effects, and promising early clinical data, they offer an exciting alternative to traditional anabolic steroids—particularly for:

• Muscle wasting diseases

• Age-related decline in strength and bone health

• Breast cancer and neurodegenerative disease research

That said, SARMs are still investigational compounds, and should only be used under the guidance of a healthcare provider or in a clinical setting.

SARMs vs Steroids

• SARMs offer tissue-specific anabolic effects, reducing risk of prostate enlargement, virilization, and cardiovascular strain.

• Anabolic steroids, by contrast, often lead to:

  • Elevated estrogen (via aromatization)

  • DHT-related side effects

  • Suppression of natural hormone production

  • Liver toxicity (especially oral forms)

Side Effects of SARMs

Shared Androgenic Risks

Despite their selectivity, SARMs can still cause androgenic side effects due to systemic activity at high doses or prolonged use:

• Acne

• Mood changes

• Libido fluctuations

• Hair thinning

• Gynecomastia (due to hormonal imbalance)

• Testicular atrophy (dose-dependent suppression of LH/FSH)

Hormonal Suppression

SARMs suppress:

• Luteinizing hormone (LH)

• Follicle-stimulating hormone (FSH)

• Endogenous testosterone

This can disrupt the testosterone:estrogen balance, especially since SARMs don’t aromatize but can indirectly cause estrogen dominance.

Cardiometabolic Risks

• Dose-dependent reduction in HDL, LDL, and triglycerides

• Possible elevation in blood pressure

• Impact on sex hormone-binding globulin (SHBG)

Liver Toxicity

While SARMs are not hepatotoxic at therapeutic doses, high dosages or prolonged cycles may lead to:

• Mild increases in AST and ALT enzymes

• Rare liver strain in sensitive individuals

Overall, SARMs have fewer hepatic risks than 17α-alkylated oral steroids (Basaria, 2010).

Post Cycle Therapy (PCT)

PCT is strongly recommended to restore hormonal balance and prevent rebound side effects:

• Clomid (Clomiphene Citrate)

• Nolvadex (Tamoxifen)

• Natural test boosters

Clinical Research and Regulatory Status (as of Q3 2023)

The FDA requires functional outcomes (not just muscle mass gains) for approval, making trial design difficult and costly.

SARMs represent a promising evolution in anabolic therapies. While still under clinical investigation, their potential for treating:

• Muscle wasting

• Osteoporosis

• Breast cancer

• Neurodegeneration is unmatched by conventional AAS.

However, SARMs should be approached cautiously and only used under clinical guidance or with a thorough understanding of risks and proper PCT protocol.

SARMS: Takeaway

SARMS have shown to have powerful tissue-selective anabolic effects. Clinical study and evaluation has shown a high binding affinity and the ability to build muscle mass at an impressive rate, more so than some anabolic agents. 

SARMS are still investigational and are not intended for use, but for research purposes only. Long term toxicity studies have not been conducted, therefore it is impossible to know the long term side effects. 

All agents that promote anabolism, will have some degree of liver toxicity, and elevated liver enzymes, above clinical therapeutic dosages. 

SARMs do not undergo aromatization to estrogen or 5-alpha reduction, which can result in unfavorable hormonal levels, suppressing natural testosterone levels as well as luetenizing hormone, FSH, and SHBG. 

This article is for informational and research purposes only. We do not sell, nor promote the use of SARMS or experimental drugs for research design. 

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