SARMs Education, the Great the Good the Bad and the Ugly – Liver Toxicity 101

Lets call it ” The Truth” as opposed to the ” Sales Pitch”

ALL SARMs must be considered Liver Toxic

The 3 major Therapeutic Concerns of using SARMs

The dissociation from a steroidal back bone and the development of tissue selectivity may enable Non Steriodal SARMs to overcome many of the previous limitations of androgen therapies.

However, some therapeutic concerns remain even in light of dynamic SARM pharmacology. Novel liabilities unique to SARMs have also arisen of particular consideration are AR polymorphisms known to dictate AR response.

Our concerns here are…

Impact of AR polymorphisms known to dictate AR response.
Liver Toxicity
The effects of Androgen Therapy on Lipid Profiles – an affect that principally occurs with Oral Administration and in a dosage dependant manner

On the subject of Liver Toxicity

A major therapeutic limitation of traditional androgen therapies, ie Steroidal SARMs is liver toxicity.

Chemical modifications made to the 17 carbon in Testosterone protect the parent molecule from metabolism, allows for oral application but can result in severe liver toxicity.

Studies have suggested this hepatotoxicity is common to the 17α alkyl group found in a number of steroid analogs and not due to increased liver exposure from oral dosing.

Non steroidal AR antagonists are also plagued by a host of liver pathologies including; cirrhosis, hepatitis, and even heptocellular carcinoma

The clinical evaluation of numerous steroidal analogs suggests that varied structure and/or dosage formulations could circumvent this problem, though some concerns of liver toxicity exist

The liver toxicity of SARMs, whose appeal is due in part to orally availability, remains largely unknown, though flexibility in the pharmacophore is promising in terms of evaluating various efficacious molecules for adverse liver effects.

Make no mistake we are starting to see the first Case Studies in Human Cohorts of Liver Stress.

RAD-140 + LGD-4033 Liver Toxcity

LGD-4033 Liver Toxicity

Takeaway ?

Hepatotoxicity is a serious adverse reaction potentially induced by all antiandrogens.

SARMs are Non Steroid Androgen Receptor Ligands that are derived from Anti-Androgens

Multiple nonsteroidal SARMs have been developed to date including compounds from the following Chemical Skeletal Structures

Aryl Propionamides, Bicyclic Hydantoins, Bicyclic Thiohydantoins, Imidazole Pyrazoles, Benzimidazoles, Anilines and Quinolinones.

Although there are structural differences between antiandrogens, all are potential hepatotoxic drugs.

Its a simple logical rational follow on then that we are expecting to see, looking for Liver Toxicity in exactly the same way as you would from Methylated Steroidal SARMs – ie most Oral Anabolic Steroids..

Its now simply a question of ” at what exposure level” and “too what magnitude” .. the same question we have of Oral Anabolic Steroids

When these drugs are proven safe at specific dosages we can accept that data, but you need to go in ” expecting” Liver Toxicity until we have data to support “long term, safe use”

That is the rationale of using Anti-Androgen Backbones, they ” come” with Hepatoxicity, virtually by default..

Victor Black