Written by DR. GEORGE TOULIATOS, MD
31 March 2020

 LIVER-TOXICITY-UNDER-AAS-ABUSE

 

Dr. Testosterone
By George Touliatos, MD

 

LIVER TOXICITY UNDER AAS ABUSE

 

Anabolic-androgenic steroids (AAS) in their majority are responsible for a wide variety of clinical and pathological hepatic strain. Alkylation of the steroid molecule ensures that the particular substance will sustain the detoxification process of the liver, right after its entrance through the portal vein. This alkylation stresses the organ and transaminemia occurs (ALT/AST-SGOT/SGPT>100). Liver damage is further characterized into hepatocellular (ALT/AST elevation) and cholestatic (ALP/GGT rise).

 

The 17alpha-alkylated AAS have been associated with cases of liver damage such as cholestatic jaundice, hepatic peliosis, hepatic adenoma and carcinoma. Oxymetholone (ANADROL 50) and methyltestosterone (DIANABOL) have frequently been linked to hepatocellular carcinoma. Stanozolol (WINSTROL) causes liver damage (inflammatory or degenerative lesions in hepatocytes).

 

On the other side, cholestasis induced by esterified testosterone and 19-nortestosterone derivatives (DECA, TREN) is quite rare, although their prolonged use may increase the risk of hepatic tumors.

AAS and especially the 17alpha-alkylated have been associated with four distinct forms of liver injury:

 

• Pharmaceutical hepatitis: Elevation of transaminases (SGOT, SGPT/AST, ALT), mainly by 17alpha-alkylated AAS per os (oxandrolone, stanozolone, methadrostenolone, oxymetholone, methyltestosterone, methyltrienolone-M3).

 

• GGT is the most distinctive enzyme for the detection of hepatic dysfunction.

 

• These elevations attributed to the intake of oral steroids are usually asymptomatic, transient and return to baseline levels within several weeks after cessation.

 

• Cholestasis => obstructive jaundice.

 

Clinical symptoms include nausea, fatigue, itching followed by dark-brownish urine (elevated urobilinogen) and jaundice (yellowing of the eye’s sclera, skin-elevated bilirubin). Jaundice can be prolonged, even if AAS are discontinued. Serum elevations of cholestatic markers (ALP, GGT, bilirubin-direct/indirect) are present.

 

Cholestasis has been described as benign, but fatal cases have been reported. In most of cases, cholestasis induced by AAS is a result of a change in hepatocyte biliary secretion and generally is not associated with hepatocellular damage.

 

The development of cholestatic jaundice is predictable and related to dose and treatment duration; it may occur in a low percentage of patients assuming 17alpha-alkylated steroids. Cholestatic jaundice is usually transient and can be completely healed upon discontinuation of AAS.

 

• Hepatic peliosis: rare syndrome where liver lobes are covered with nodulation-containing blood cysts. The liver may be enlarged, deep red in color. Serum enzyme levels are usually normal or mildly elevated. Patients may present with right upper discomfort and hepatomegaly. Sudden abdominal pain and vascular collapse due to hepatic rupture and hemoperitoneum is a rare complication, but sometimes fatal. However, peliosis associated with AAS usually reverses, at least in part, in case of AAS discontinuation.

 

• Hepatocellular carcinoma: the most serious complication of AAS use is the development of hepatic tumors, either adenoma (HCA) or carcinoma (HCC). Clinical presentation is generally with right upper quadrant discomfort and a hepatic mass found clinically or on imaging studies (U/S, C/T). Routine liver tests are often normal, unless there is extensive spread or rupture or any accompanying liver disease. While fluoxymesterone (HALO) is associated with HCA formation, other substances like oxymetholone and methyltestosterone respectively can lead to HCC. The hepatic tumors arise in patients on long-term AAS use. In cases with pre-existing pathologies (e.g., hepatitis B), the liver tumor appearance can be shorter. Both parenteral and oral AAS may induce hepatic neoplasms. There are different therapeutic strategies for HCC without metastasis. In general, liver transplantation is the therapy of choice for selected patients with HCC without the possibility of extrahepatic metastasis. Abuse of AAS over a long period of time has a great risk of developing an HCC and users should therefore be well monitored. Periodic hepatic ultrasound seems to be an adequate screening procedure to detect the development of hepatic lesions.

 

Hepatic parenchyme toxicity and liver strain, in general, may be correlated to individual susceptibility, genetic factors and polydrug use. So during the period of the pre-contest preparation, the athlete should abstain from hepatotoxic substances such as alcohol, acetaminophen and nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen. Furthermore, he should use hepatoprotective supplements with meals, since supplementation provides medical prevention and ensures that liver enzymes are not that much elevated (20%).

 

Hepatoprotective supplementation includes:

 

1. Ursodeoxycholic acid (UDCA) is a bile salt mainly used in the formula of cholestatic liver disorders. It reduces cholesterol in bile and stones, and reduces the excretion of cholesterol from liver cells and reabsorption in the gut. It is useful in cases of cholestasis, and improves clinical symptoms of jaundice and liver biochemistry as well.

 

2. Glutathione (GSH) is a tripeptide consisting of three amino acids (glutamine, cysteine, glycine) and is the most powerful antioxidant in nature. It prevents oxidation of red blood cells, helps in detoxification of the liver parenchyma, strengthens the immune system, improves skin quality, brain metabolism and is frequently used as an anti-aging agent.

Glutathione’s action in the liver ensures the removal of the toxic waste products and neutralizes free radicals reactive oxygen compounds and heavy metals. Injectable administration of glutathione ensures its direct action, compared to the oral form, where part of it is degradated by gastric fluid.

 

3. N-acetyl cysteine (NAC) is a precursor of glutathione and used to increase the glutathione reserves in the body. NAC is also effective in reducing death rate and preventing permanent harm caused by acetaminophen poisoning.

 

4. Alpha-lipoic acid is a potent antioxidant, which has also been shown to restore glutathione and vitamin levels (vitamin E, C). Therefore, it’s a potent agent against free radicals and oxidative stress.

 

5. Silymarin (silymarin-milk thistle) is a hepatoprotective substance with multiple actions. It stabilizes the membrane of liver cells by preventing the entry of toxins into the body. It increases cell regeneration in the liver and stimulates the synthesis of proteins. This results in increasing the production of new liver cells to replace the old damaged cells. It helps prevent the depletion of glutathione in liver cells. Finally, it promotes the flow of bile from the liver to the intestine, which then cleaves the fats from food.

 

Silymarin is used in several of the stages of hepatotoxicity by AAS as in pharmaceutical hepatitis in fatty infiltration of the liver and cirrhosis. It does not offer substantially though, in cases of cholestasis.

6. Liv-52 is a mixture of herbal preparation. It is effective in cases of drug hepatitis, non-alcoholic fatty liver disease and cirrhosis. It protects hepatic parenchyma and promotes regeneration of liver cells. Its protective effect can be attributed to its diuretic effect too.

 

George Touliatos, MD is an author, lecturer, champion competitive bodybuilder and expert in medical prevention regarding PED use in sports. Dr. Touliatos specializes in medical biopathology and is the medical associate of Orthobiotiki.gr and Medihall.gr, Age Management and Preventive Clinics in Athens, Greece. Heis the author of four Greek books on bodybuilding, has extensively developed articles for www.anabolic.org and is the medical associate for the book Anabolics, 11th Edition (2017). Dr. Touliatos has been a columnist for the Greek editions of MuscleMag and Muscular Development magazines, and has participated in several seminars across Greece and Cyprus, making numerous TV and radio appearances, doing interviews in print and online. His personal website is https://gtoul.com/

 

 

 

 

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