Anabolic Steroid Effect on the liver

Title of Article: Anabolic Steroid Effect on the Liver

Journal: Current Sports Medicine Reports (2018)

Key Findings:

1. Anabolic steroids can cause adverse effects on the liver, including elevated liver function tests, acute cholestatic syndrome*, peliosis hepatis, hepatic adenoma*, hepatocellular carcinoma, and toxicant-associated fatty liver disease.

2. Adverse effects on the liver are linked to 17-alpha-alkylated testosterones.

3. Both long-term and short-term use of anabolic steroids can increase the risk for atherosclerotic* disease.

4. Increased risk of atherosclerotic disease is linked to decreased high-density lipoprotein (HDL) and lipoprotein A.

*Cholestasis: decreased flow of bile due to impaired bile secretion or obstruction of bile flow (Fig. 1)*Adenoma: a benign tumor consisting of glandular structures*Atherosclerosis: a disease of the arteries that is characterized by deposition of fatty plaques in the walls of arteries

Background

Testosterone is known as the “male sex hormone” and produces desirable anabolic effects in athletes such as increased muscle mass and decreased fat mass. Testosterone produces its effects in the human body by binding to androgen receptors in cells. Anabolic steroids are generally man-made so that they are structurally related to testosterone and have the ability to bind to androgen receptors. Drug-tested sports today have banned the use of anabolic steroids, as they are deemed performance-enhancing agents with potential for abuse by athletes.

Anabolic steroids work mainly in three facets: 1) increase body’s use of protein to build muscle, 2) prevent the body from undergoing breakdown of muscle, and 3) increase aggression. These pharmacologic agents are classified as schedule 3 drugs by the United States Drug Enforcement agency. Physicians and other healthcare workers are concerned about athletes using anabolic steroids because users are hesitant to approach physicians for advice, users tend to take doses well beyond therapeutic levels, and the use of the drugs are linked to several health ailments.

Anabolic steroids are eliminated and broken down primarily by the liver (Fig. 2). There are four forms of liver injury associated with anabolic steroids: liver function test elevations, chronic vascular injury (peliosis hepatis), hepatic adenoma, and hepatocellular carcinoma (liver cancer). Injectable forms of anabolic steroids are much more highly associated with adverse effects on the liver and injection is the most common form of use. Oral anabolic steroids are better tolerated by the human body and have fewer side effects.

Figure 1. Liver Anatomy

The liver is normally located in the right upper quadrant of the abdomen.

Figure 2. Bile Flow

Bile comes comes from the gallbladder and is released into the intestines and is recycled back to the liver.

Elevated Liver Enzymes

Anabolic steroid use is associated with increased blood levels of liver enzymes, including aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), and gamma glutamyl transpeptidase (GGT). The elevation in these enzymes indicates damage to liver cells called hepatocytes. Elevations in another enzyme, called creatine kinase (CK), are not associated with steroid use in regular exercise. However, CK may still be increased in anabolic steroid users because users tend to undergo more rigorous workout regimens, which may precipitate a very serious condition called rhabdomyolysis. Rhabdomyolysis is the breakdown of damaged skeletal muscle, a condition seen in patients who exercise beyond their muscles’ limits and patients who have seizures. Stopping anabolic steroids may reverse liver enzyme elevations over time.

Acute Cholestatic Syndrome

Anabolic steroids often contain a 17-alpha-alkyl group, allowing the drug to bypass the liver’s first-pass metabolism effect. This bypass is highly associated with decreased flow of bile (Fig. 1). Patients tend to present with a slow progression of nausea, tiredness, itchiness, followed by dark urine and yellowing of the skin. This type of liver damage is generally minimal and reversible.

Peliosis Hepatis

Recall that this is referred to as chronic vascular injury of the liver. What happens is that the liver develops a wound with a high density of blood vessels. These rarely bleed into the abdomen. Cessation of steroids can reverse these effects.

Tumors

Two tumors associated with anabolic steroid use are hepatic adenoma and hepatocellular carcinoma. Hepatic adenomas are benign tumors of the liver and may undergo transformation to more serious tumors that can spread throughout the body, a term called “malignant transformation.” Hepatocellular carcinoma is also known colloquially as liver cancer; it has the potential to spread through the blood and to other organs of the body.

Toxicant-Associated Fatty Liver Disease (TAFLD)

Anabolic steroids are associated with TAFLD; however, the current mechanism is unclear. Studies have suggested that it is due to direct toxicity to liver cells from long-term use.

Cholesterol

Use of anabolic steroids is associated with decreased levels of HDL (commonly referred to as “good cholesterol”) and lipoprotein A. HDL normally takes cholesterol from peripheral organs and brings it back to the liver. It works essentially like a pipe cleaner. Lipoprotein A reductions are associated with increased deposition of fat into blood vessel walls. Overall, these effects promote atherosclerosis. Although current research has yet to come to a conclusion if the decrease in HDL and lipoprotein A increase risk for cardiovascular disease, it is more likely than not to do just that.

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