Vision
10-13-2015, 10:22 PM
Declaimer: These results are typical for adult men. Normal results may vary slightly from laboratory to laboratory
Ladies and Gents, First and foremost I'd like to stress the absolute importance of getting lab/bloods done regularly, not just when on, but when off as well..
However,the absolute importance of getting bloods done when on to assure your liver functions are where they should be..
(Below is some information in regards to this topic, also provided is some spec charts along with some basic laboratory values)
Team PSL,
Vision
How to Read Your Liver Blood Test Results
Alright everyone, lets talk about blood tests. Bloodtests can be very useful for your longevity as a juicer. Regular bloodtests can go a long way to preserving your health while you get huge, as well as giving you early warning signs if your body is under stress. It is very easy to go for months of being on sauce and not going off or getting a blood test. Bloodtests are extremely important. Please utilize them. This is how to read your bloodtest regarding your liver. Remember, your liver is your primary filtering organ of your entire system. Everything you eat drink, and every drug you take is eventually filtered by your liver. Without a healthy liver, you cannot have a healthy body, none the less a huge one. So read on and pay attention. When you get your blood work done, always ask your doctor for a copy so you can examine it for yourself. If you have an alarmist for a doctor, you will definitley want to determine the results for yourself. Many doctors who are unfamiliar with anabolic steroids will tell you that you are going to die from slightly elevated AST or ALT enzymes. What is an AST or ALT enzyme? Read on...
Aminotransferases also known as Transaminases- Liver Enzymes
Alanine Aminotransferase (ALT or SGPT)
ALT is more liver specific than AST. When this enzyme is elevated, there is a good chance that your liver is under stress or may be damaged. There are only low concentrations of this enzyme in skeletal muscles and in the kidney. This enzyme has one is said to be a high 'specificity' for liver stress/strain.
Aspartate Aminotransferase (AST or SGOT)
AST is found more abundantly in the kidney and in skeletal muscle, brain and red blood cells. For this reason, an elevated level of AST is not as SPECIFIC for liver damage/stress as is ALT. However, elevated AST in the presence of elevated ALT heightens the likelihood that liver damage or stress is present.
Cholestatic Enzymes:
Alkaline Phosphatase (ALP or AP) and Gamma-glutamyl Transferase (GGT)
ALP is found in high concentrations in bone and liver. Lesser amounts are present in the intestines, kidneys or leukocyets (white blood cells). ALP is not a huge marker of liver damage unless it is accommodated by other elevated liver enzymes.
Gamma-glutamyl Transferase (GGT)
GGT is found mostly in the liver. It is one of the biggest markers of liver function. GGT is a microsomal enzyme that is very sensitive to hepatotoxic drugs (for our purposes, anabolic steroids). Elevated GGT in the presence of elevated AST and more specifically ALT tell us to back off the juice and give it a break for a while. In this case, you should have your blood tested before beginning another cycle, even after your break. By doing this, you make sure that the liver has had a chance to regenerate itself before stressing it again with anabolics (especially if you are planning to use orals).
Here are some normal figures for these enzymes based off my most recent personal blood test and how you will see them on your blood test:
ALT normal range is 10-40 U/L (units per liter)
AST normal range is 15-50 U/L (units per liter)
ALP normal range is 37-116 U/L (units per liter)
GGT normal range is 3-60 IU/L (international units per liter)
and an other as test to demonstrate that labs will vary
ALT. 7 to 55 units per liter (U/L)
AST. 8 to 48 U/L
ALP. 45 to 115 U/L
Albumin. 3.5 to 5.0 grams per deciliter (g/dL)
Total protein. 6.3 to 7.9 g/dL
Bilirubin. 0.1 to 1.0 mg/dL
GGT. 9 to 48 U/L
LD. 122 to 222 U/L
PT. 9.5 to 13.8 seconds
So, make sure to look at the AST and ALT numbers, they are on every basic blood test. The GGT enzyme is not always on the blood test, doctors have to mark this one specifically, and unless they suspect that something is wrong, do not usually order this enzyme to be tested. You can ask them to test this one for you. However, if your AST and ALT are both within the normal range, you can be 99% assured that nothing is wrong with your liver.
If AST and ALT are elevated out of the normal range, at the very least, go off the juice for a while. It would be smart at this point to get another blood test with GGT included to confirm whether or not the liver is truly under damage. Remember, the most accurate way to know if your liver is damaged/stressed, is to look at the AST/ALT numbers and also the GGT. If all of them are high, you better take a break until they are under control. At the very least, you will want the GGT to be in normal range before going back on the sauce. Remember, GGT is the most accurate predictor of liver stress when accomodated by elevated AST or ALT (either one or both enzymes).
While you are off you will want to pay special attention to your anti-oxidant intake and take a good daily dosage of silymarin (milk thistle). The amino acid NAC also has hepato-protective and reguvenative effects. NAC at a dose of 600mg twice per day and milk thistle, at least 125mg standard extract twice per day. Drink plenty of water as well-at least .5ounces per pound of bodyweight.
__________________________________________________ _____________________________
OVERVIEW
Anabolic Steroids
Introduction
Androgenic steroids are used for male sex hormone replacement and in the therapy of malignancies. The androgens also have anabolic effects and are used in catabolic or muscle wasting states. The synthetic anabolic steroids are also widely used illicitly for body building. Many synthetic androgenic steroids are capable of causing cholestatic liver injury and long term use of androgens is associated with development of liver tumors including hepatocellular carcinoma and hepatic adenoma.
Background
Testosterone is the major male sex hormone and is produced by the male testes in men and to a lesser extent by the adrenal glands in both men and women. Unmodified testosterone is not orally available, so it must be given intramuscularly, sublingually or transcutaneous patch. Modifications of testosterone have been developed that are more bioavailable or have a longer duration of action. Modification by esterification (testosterone cypionate, enanthate and propionate) maintains the virilizing effects of testosterone, but increases potency and duration of action. Alkylation of the C-17 position of testosterone allows for oral administration and often alters the relative anabolic potency in relation to the masculinizing effects. The C-17 alkylated testosterones include methyltestosterone, methandrostenolone, oxymetholone, danazol, fluoxymesteone, stanazol, norethandrolone and oxandrolone, and have been extensively evaluated as a means of increasing weight gain and muscle development in catabolic states as well as to improve athletic performance. They have also been used to treat aplastic anemia and bone marrow failure of several causes. They are often well tolerated and have limited virilizing activity. However, the C-17 alkylated androgenic steroids have all been implicated in cases of liver injury, including prolonged cholestasis, peliosis hepatis, nodular regeneration, hepatic adenomas and hepatocellular carcinoma. In contrast, the esterified testosterones have only rarely been implicated in causing cholestasis, although their long term use may increase the risk of hepatic tumors and nodular transformation, but seemingly at a much lower rate than the 17-alkylated testosterones. Current uses of androgenic steroids include androgen deficiency, breast cancer, postpartum breast engorgement, hereditary angioneurotic edema, endometriosis and fibrocystic breast disease. The androgenic steroids are also used off label and illegally as a means of increasing muscle mass and athletic performance. The abuse of anabolic steroids is particularly common among body builders and young male athletes, although their use has been banned from the Olympics and in major professional and college sports. Recently, anabolic steroids have been found in some nutritional supplements available over-the-counter or via the internet which are advertised as increasing a sense of well being and muscle mass.
Hepatotoxicity
Androgenic and anabolic steroids have been implicated in four distinct forms of liver injury: transient serum enzyme elevations, an acute cholestatic syndrome, chronic vascular injury to the liver (peliosis hepatis) and hepatic tumors including adenomas and hepatocellular carcinoma. These adverse events have been most closely linked with the C-17 alkylated testosterones, although tumors have also been associated with unmodified and esterified testosterone preparations.
Use of androgenic steroids is associated with a variable rate of serum enzyme elevations which are usually asymptomatic and self limited. Such elevations have been most closely linked to danazol and oxymethalone, but are usually transient and do not require dose adjustment or discontinuation.
More importantly, therapy with anabolic steroids is linked to a distinctive form of acute cholestasis. The liver injury generally arises within 1 to 4 months of starting therapy, but may be delayed to as long as 6 to 24 months. The onset is usually insidious with development of nausea, fatigue and itching followed by dark urine and jaundice. Jaundice and pruritus can be prolonged even if the anabolic steroids are discontinued promptly. Typically, serum enzyme elevations are quite modest, with ALT and alkaline phosphatase levels that are less the 2 to 3 times elevated and that are sometimes normal despite deep jaundice. Serum ALT levels may be somewhat high early during injury, but then fall to moderate or low levels. Liver biopsy typically shows a bland cholestasis with minimal inflammation and hepatocellular necrosis. Bile duct injury is typically absent or mild and vanishing bile duct syndrome rarely ensues. The frequency of acute cholestasis from androgenic steroids is not well known, but it is likely somewhat dose related and may occur in ~1% of patients treated with methyltestosterone, danazol, stanozolol or oxymetholone. Cholestasis has not been described in patients receiving unmodified testosterone (by injection or transdermal patch). This clinical phenotype of bland cholestasis is so typical of anabolic steroids, that the diagnosis can be suspected in a patient who denies taking anabolic steroids or who is taking an herbal formulation meant to increase muscle strength or energy and that contains an anabolic steroid even though it is not labelled as such.
Use of anabolic steroids has also been linked to vascular changes in the liver referred to as peliosis hepatis. Peliosis hepatis is a rare syndrome in which there are blood filled enlarged sinusoids and cysts focally or throughout the liver. There is usually an accompanying sinusoidal dilatation and loss of the normal endothelial barrier. The liver may be enlarged, deep red in color and fragile. Peliosis hepatis most typicaly occurs in patients with advanced wasting diseases (tuberculosis, cancer), but has also been associated with long term use of anabolic steroid therapy for aplastic anemia and hypogonadism as well as in body building. Serum enzyme levels are usually normal or are mildly and nonspecifically elevated. Patients may present with right upper quadrant discomfort and hepatomegaly or with sudden abdominal pain and vascular collapse due to hepatic rupture and hemoperitoneum. Peliosis may also be an incidental finding found on imaging of the liver or during abdominal surgery or at autopsy. Peliosis associated with anabolic steroids usually reverses, at least in part, with stopping therapy. Peliosis can involve other organs, most typically the spleen.
The most serious complication of anabolic steroid use is the development of hepatic tumors, either adenoma or hepatocellular carcinoma. The hepatic tumors arise in patients on long term androgenic steroids, usually during therapy of aplastic anemia or hypogonadism, but occasionally in athletes or body builders using anabolic steroids illicitly. Tumors are typically found after 5 to 15 years of use, but onset within 2 years of starting therapy with testerosterone esters has been described. Many of the case reports have occurred in patients with other risk factors for cancer, such as Fanconi?s syndrome, iron overload or chronic hepatitis C (from blood transfusions). However, hepatic adenomas and hepatocellular carcinoma have also been described in patients taking androgenic steroids who have no other evidence of liver disease and normal histology in the nontumor parts of the liver. The pathology of the tumors is usually hepatic adenoma or ?well differentiated? hepatocellular carcinoma or hepatic adenoma with areas of malignant transformation. Rare instances of cholangiocarcinoma and angiosarcoma have also been described in patients on long term androgenic steroids. Clinical presentation is generally with right upper quadrant discomfort and a hepatic mass found clinically or on imaging studies. Routine liver tests are often normal unless there is extensive spread or rupture or an accompanying liver disease. Alphafetoprotein levels are usually normal. There is often (but not always) spontaneous regression in the tumor when the anabolic steroids are stopped. Hepatocellular carcinoma arising during anabolic steroid therapy is believed to have a better prognosis than that related to cirrhosis or chronic hepatitis B and C; however, deaths from hepatic rupture or tumor spread and metastasis have been reported in patients with anabolic steroid related hepatocellular carcinoma without cirrhosis.
Finally, nodular regenerative hyperplasia of the liver has been described in rare patients on long term anabolic or androgenic steroids. The condition is usually asymptomatic or associated with mild abdominal discomfort due to hepatomegaly. Rarely, marked nodular regenerative hyperplasia with portal hypertension and splenomegaly has been described. This process may also be related with development of hepatic tumors with androgenic steroids as nodular regeneration is sometimes found in the surrounding ?normal? liver.
Mechanism of Injury
The androgens act by engagement of intracellular androgenic steroid receptors which are translocated to the nucleus and attach to androgen response elements on DNA inducing a cassette of androgen stimulated genes that are important in cell growth and development. An unregulated growth stimulus to hepatocytes is the likely cause of nodular regeneration and hepatic tumors related to anabolic steroid use. The cause of cholestasis due to the C-17 substituted androgens is not well defined, but high doses cause a similar cholestasis in some animal models. The syndrome is similar to cholestasis of pregnancy and the jaundice associated with high doses of estrogens or birth control pills and may be due to partial lack or variant of bile salt transporter proteins.
Outcome and Management
The severity of liver injury due to anabolic steroids ranges from minor, transient serum enzyme elevations to profound and prolonged cholestasis, as well as hepatic peliosis and benign and malignant liver tumors. The first priority in management should be stopping the androgenic steroid. Unfortunately, athletes and body builders may resist this recommendation. Merely decreasing the dose of androgenic steroid or switching to another formulation is not appropriate and should be specifically discouraged. Patients being treated for hypogonadism may be switched to an unmodified form of testosterone, given by injection or cutaneous patch. Patients with marked cholestasis may be benefitted by symptomatic therapy of pruritus and fat soluble vitamin supplementation. Ursodiol is often used in drug induced cholestasis, but is efficacy has never been shown in a controlled prospective manner. Use of corticosteroids is usually ineffective and should be avoided. The syndrome is usually reversable with stopping therapy, but recovery is often protracted. In addition, fatalities have been reported, usually due to marked cholestasis complicated by malnutrition, renal failure and associated opportunitistic infections.
Representative androgenic steroids include the following: danazol, fluoxymesterone, methandienone, methenolone, methyltestosterone, nandrolone, norethandrolone, oxandrolone, oxymetholone, stanozolol, testosterone (cypionate, enanthate, propionate).
Drug Class: Anabolic Steroids
Case Report
Anabolic Steroids
Case 1. Cholestasis due to anabolic steroid use.
[Modified from: Singh C, Bishop P, Wilson R. Extreme hyperbilirubinemia associated with the use of anabolic steroids, health/nutritional supplements and ethanol: response to ursodeoxycholic acid treatment. Am J Gastroenterol 1996; 91: 783-5. PubMed Citation (http://www.ncbi.nlm.nih.gov/pubmed/8677950)]
A 24 year old body builder developed pruritus and jaundice having taken various anabolic steroids for one and a half years. He was also taking several herbal products and dietary supplements including Ma Huang (6% ephedrine), carnitine and chromium. He also drank alcohol, estimating his average intake as one case of beer per day for the last year. He developed dark urine and jaundice and stopped all medications and his alcohol intake promptly. Despite this, he remained jaundiced for a month and had worsening nausea and weight loss and eventually sought medical care. He had no history of liver disease or risk factors for viral hepatitis and took no other medications. On examination, he was muscular and physically fit but deeply jaundiced. He had an enlarged liver but no rash, fever or splenomegaly. Laboratory testing showed a total serum bilirubin of 53 mg/dL, but only modest elevations in serum aminotransferase and a normal alkaline phosphatase level (Table). His prothrombin time was normal. Tests for hepatitis A, B and C were negative. Abdominal ultrasound showed no evidence of biliary obstruction. Liver biopsy was not done. He was treated symptomatically for pruritus with antihistamines, cholestryamine and ursodiol. His jaundice gradually improved and pruritus waned. Six months after the onset of jaundice, he was asymptomatic, had regained most of his weight loss (40 pounds), serum bilirubin was 1.5 mg/dL and serum enzymes were normal.
Key Points
Medication:
Anabolic steroids (nandrolone, stanozolol)
Pattern:
Bland cholestasis
Severity:
3+ (jaundice, hospitalization)
Latency:
16 months
Recovery:
0.6 months
Other medications:
Various herbal products and dietary supplements
Laboratory Values
Time After Stopping
ALT
(U/L)
Alk P
(U/L)
Bilirubin
(mg/dL)
Other
Anabolic agent use for ~1.5 years
6 weeks
237
129
21
8 weeks
90
121
53
10 weeks
203
91
51
Ursodiol started
12 weeks
119
81
22
14 weeks
116
67
8
4 months
58
50
4
5 months
33
75
1.5
Asymptomatic
Normal Values
<56
<139
<1.2
Comment
A very typical case of severe cholestasis due to anabolic steroid use. Because the steroids were being used without medical supervision, the dose and actual duration of use of each preparation was unclear, but cholestasis usually arises within 4 to 12 weeks of starting a C-17 alkylated androgenic steroid. The jaundice can be severe and prolonged and accompanied by severe pruritus and marked weight loss. The serum enzymes are typically minimally elevated except for a short period immediately after stopping therapy. The pattern of enzyme elevations can be hepatocellular, cholestatic or mixed. Liver biopsy shows a ?bland? cholestasis with minimal inflammation and hepatocellular necrosis. Ma Huang has also been implicated in cases of drug induced liver injury, but is associated with an acute hepatocellular pattern of injury.
Ladies and Gents, First and foremost I'd like to stress the absolute importance of getting lab/bloods done regularly, not just when on, but when off as well..
However,the absolute importance of getting bloods done when on to assure your liver functions are where they should be..
(Below is some information in regards to this topic, also provided is some spec charts along with some basic laboratory values)
Team PSL,
Vision
How to Read Your Liver Blood Test Results
Alright everyone, lets talk about blood tests. Bloodtests can be very useful for your longevity as a juicer. Regular bloodtests can go a long way to preserving your health while you get huge, as well as giving you early warning signs if your body is under stress. It is very easy to go for months of being on sauce and not going off or getting a blood test. Bloodtests are extremely important. Please utilize them. This is how to read your bloodtest regarding your liver. Remember, your liver is your primary filtering organ of your entire system. Everything you eat drink, and every drug you take is eventually filtered by your liver. Without a healthy liver, you cannot have a healthy body, none the less a huge one. So read on and pay attention. When you get your blood work done, always ask your doctor for a copy so you can examine it for yourself. If you have an alarmist for a doctor, you will definitley want to determine the results for yourself. Many doctors who are unfamiliar with anabolic steroids will tell you that you are going to die from slightly elevated AST or ALT enzymes. What is an AST or ALT enzyme? Read on...
Aminotransferases also known as Transaminases- Liver Enzymes
Alanine Aminotransferase (ALT or SGPT)
ALT is more liver specific than AST. When this enzyme is elevated, there is a good chance that your liver is under stress or may be damaged. There are only low concentrations of this enzyme in skeletal muscles and in the kidney. This enzyme has one is said to be a high 'specificity' for liver stress/strain.
Aspartate Aminotransferase (AST or SGOT)
AST is found more abundantly in the kidney and in skeletal muscle, brain and red blood cells. For this reason, an elevated level of AST is not as SPECIFIC for liver damage/stress as is ALT. However, elevated AST in the presence of elevated ALT heightens the likelihood that liver damage or stress is present.
Cholestatic Enzymes:
Alkaline Phosphatase (ALP or AP) and Gamma-glutamyl Transferase (GGT)
ALP is found in high concentrations in bone and liver. Lesser amounts are present in the intestines, kidneys or leukocyets (white blood cells). ALP is not a huge marker of liver damage unless it is accommodated by other elevated liver enzymes.
Gamma-glutamyl Transferase (GGT)
GGT is found mostly in the liver. It is one of the biggest markers of liver function. GGT is a microsomal enzyme that is very sensitive to hepatotoxic drugs (for our purposes, anabolic steroids). Elevated GGT in the presence of elevated AST and more specifically ALT tell us to back off the juice and give it a break for a while. In this case, you should have your blood tested before beginning another cycle, even after your break. By doing this, you make sure that the liver has had a chance to regenerate itself before stressing it again with anabolics (especially if you are planning to use orals).
Here are some normal figures for these enzymes based off my most recent personal blood test and how you will see them on your blood test:
ALT normal range is 10-40 U/L (units per liter)
AST normal range is 15-50 U/L (units per liter)
ALP normal range is 37-116 U/L (units per liter)
GGT normal range is 3-60 IU/L (international units per liter)
and an other as test to demonstrate that labs will vary
ALT. 7 to 55 units per liter (U/L)
AST. 8 to 48 U/L
ALP. 45 to 115 U/L
Albumin. 3.5 to 5.0 grams per deciliter (g/dL)
Total protein. 6.3 to 7.9 g/dL
Bilirubin. 0.1 to 1.0 mg/dL
GGT. 9 to 48 U/L
LD. 122 to 222 U/L
PT. 9.5 to 13.8 seconds
So, make sure to look at the AST and ALT numbers, they are on every basic blood test. The GGT enzyme is not always on the blood test, doctors have to mark this one specifically, and unless they suspect that something is wrong, do not usually order this enzyme to be tested. You can ask them to test this one for you. However, if your AST and ALT are both within the normal range, you can be 99% assured that nothing is wrong with your liver.
If AST and ALT are elevated out of the normal range, at the very least, go off the juice for a while. It would be smart at this point to get another blood test with GGT included to confirm whether or not the liver is truly under damage. Remember, the most accurate way to know if your liver is damaged/stressed, is to look at the AST/ALT numbers and also the GGT. If all of them are high, you better take a break until they are under control. At the very least, you will want the GGT to be in normal range before going back on the sauce. Remember, GGT is the most accurate predictor of liver stress when accomodated by elevated AST or ALT (either one or both enzymes).
While you are off you will want to pay special attention to your anti-oxidant intake and take a good daily dosage of silymarin (milk thistle). The amino acid NAC also has hepato-protective and reguvenative effects. NAC at a dose of 600mg twice per day and milk thistle, at least 125mg standard extract twice per day. Drink plenty of water as well-at least .5ounces per pound of bodyweight.
__________________________________________________ _____________________________
OVERVIEW
Anabolic Steroids
Introduction
Androgenic steroids are used for male sex hormone replacement and in the therapy of malignancies. The androgens also have anabolic effects and are used in catabolic or muscle wasting states. The synthetic anabolic steroids are also widely used illicitly for body building. Many synthetic androgenic steroids are capable of causing cholestatic liver injury and long term use of androgens is associated with development of liver tumors including hepatocellular carcinoma and hepatic adenoma.
Background
Testosterone is the major male sex hormone and is produced by the male testes in men and to a lesser extent by the adrenal glands in both men and women. Unmodified testosterone is not orally available, so it must be given intramuscularly, sublingually or transcutaneous patch. Modifications of testosterone have been developed that are more bioavailable or have a longer duration of action. Modification by esterification (testosterone cypionate, enanthate and propionate) maintains the virilizing effects of testosterone, but increases potency and duration of action. Alkylation of the C-17 position of testosterone allows for oral administration and often alters the relative anabolic potency in relation to the masculinizing effects. The C-17 alkylated testosterones include methyltestosterone, methandrostenolone, oxymetholone, danazol, fluoxymesteone, stanazol, norethandrolone and oxandrolone, and have been extensively evaluated as a means of increasing weight gain and muscle development in catabolic states as well as to improve athletic performance. They have also been used to treat aplastic anemia and bone marrow failure of several causes. They are often well tolerated and have limited virilizing activity. However, the C-17 alkylated androgenic steroids have all been implicated in cases of liver injury, including prolonged cholestasis, peliosis hepatis, nodular regeneration, hepatic adenomas and hepatocellular carcinoma. In contrast, the esterified testosterones have only rarely been implicated in causing cholestasis, although their long term use may increase the risk of hepatic tumors and nodular transformation, but seemingly at a much lower rate than the 17-alkylated testosterones. Current uses of androgenic steroids include androgen deficiency, breast cancer, postpartum breast engorgement, hereditary angioneurotic edema, endometriosis and fibrocystic breast disease. The androgenic steroids are also used off label and illegally as a means of increasing muscle mass and athletic performance. The abuse of anabolic steroids is particularly common among body builders and young male athletes, although their use has been banned from the Olympics and in major professional and college sports. Recently, anabolic steroids have been found in some nutritional supplements available over-the-counter or via the internet which are advertised as increasing a sense of well being and muscle mass.
Hepatotoxicity
Androgenic and anabolic steroids have been implicated in four distinct forms of liver injury: transient serum enzyme elevations, an acute cholestatic syndrome, chronic vascular injury to the liver (peliosis hepatis) and hepatic tumors including adenomas and hepatocellular carcinoma. These adverse events have been most closely linked with the C-17 alkylated testosterones, although tumors have also been associated with unmodified and esterified testosterone preparations.
Use of androgenic steroids is associated with a variable rate of serum enzyme elevations which are usually asymptomatic and self limited. Such elevations have been most closely linked to danazol and oxymethalone, but are usually transient and do not require dose adjustment or discontinuation.
More importantly, therapy with anabolic steroids is linked to a distinctive form of acute cholestasis. The liver injury generally arises within 1 to 4 months of starting therapy, but may be delayed to as long as 6 to 24 months. The onset is usually insidious with development of nausea, fatigue and itching followed by dark urine and jaundice. Jaundice and pruritus can be prolonged even if the anabolic steroids are discontinued promptly. Typically, serum enzyme elevations are quite modest, with ALT and alkaline phosphatase levels that are less the 2 to 3 times elevated and that are sometimes normal despite deep jaundice. Serum ALT levels may be somewhat high early during injury, but then fall to moderate or low levels. Liver biopsy typically shows a bland cholestasis with minimal inflammation and hepatocellular necrosis. Bile duct injury is typically absent or mild and vanishing bile duct syndrome rarely ensues. The frequency of acute cholestasis from androgenic steroids is not well known, but it is likely somewhat dose related and may occur in ~1% of patients treated with methyltestosterone, danazol, stanozolol or oxymetholone. Cholestasis has not been described in patients receiving unmodified testosterone (by injection or transdermal patch). This clinical phenotype of bland cholestasis is so typical of anabolic steroids, that the diagnosis can be suspected in a patient who denies taking anabolic steroids or who is taking an herbal formulation meant to increase muscle strength or energy and that contains an anabolic steroid even though it is not labelled as such.
Use of anabolic steroids has also been linked to vascular changes in the liver referred to as peliosis hepatis. Peliosis hepatis is a rare syndrome in which there are blood filled enlarged sinusoids and cysts focally or throughout the liver. There is usually an accompanying sinusoidal dilatation and loss of the normal endothelial barrier. The liver may be enlarged, deep red in color and fragile. Peliosis hepatis most typicaly occurs in patients with advanced wasting diseases (tuberculosis, cancer), but has also been associated with long term use of anabolic steroid therapy for aplastic anemia and hypogonadism as well as in body building. Serum enzyme levels are usually normal or are mildly and nonspecifically elevated. Patients may present with right upper quadrant discomfort and hepatomegaly or with sudden abdominal pain and vascular collapse due to hepatic rupture and hemoperitoneum. Peliosis may also be an incidental finding found on imaging of the liver or during abdominal surgery or at autopsy. Peliosis associated with anabolic steroids usually reverses, at least in part, with stopping therapy. Peliosis can involve other organs, most typically the spleen.
The most serious complication of anabolic steroid use is the development of hepatic tumors, either adenoma or hepatocellular carcinoma. The hepatic tumors arise in patients on long term androgenic steroids, usually during therapy of aplastic anemia or hypogonadism, but occasionally in athletes or body builders using anabolic steroids illicitly. Tumors are typically found after 5 to 15 years of use, but onset within 2 years of starting therapy with testerosterone esters has been described. Many of the case reports have occurred in patients with other risk factors for cancer, such as Fanconi?s syndrome, iron overload or chronic hepatitis C (from blood transfusions). However, hepatic adenomas and hepatocellular carcinoma have also been described in patients taking androgenic steroids who have no other evidence of liver disease and normal histology in the nontumor parts of the liver. The pathology of the tumors is usually hepatic adenoma or ?well differentiated? hepatocellular carcinoma or hepatic adenoma with areas of malignant transformation. Rare instances of cholangiocarcinoma and angiosarcoma have also been described in patients on long term androgenic steroids. Clinical presentation is generally with right upper quadrant discomfort and a hepatic mass found clinically or on imaging studies. Routine liver tests are often normal unless there is extensive spread or rupture or an accompanying liver disease. Alphafetoprotein levels are usually normal. There is often (but not always) spontaneous regression in the tumor when the anabolic steroids are stopped. Hepatocellular carcinoma arising during anabolic steroid therapy is believed to have a better prognosis than that related to cirrhosis or chronic hepatitis B and C; however, deaths from hepatic rupture or tumor spread and metastasis have been reported in patients with anabolic steroid related hepatocellular carcinoma without cirrhosis.
Finally, nodular regenerative hyperplasia of the liver has been described in rare patients on long term anabolic or androgenic steroids. The condition is usually asymptomatic or associated with mild abdominal discomfort due to hepatomegaly. Rarely, marked nodular regenerative hyperplasia with portal hypertension and splenomegaly has been described. This process may also be related with development of hepatic tumors with androgenic steroids as nodular regeneration is sometimes found in the surrounding ?normal? liver.
Mechanism of Injury
The androgens act by engagement of intracellular androgenic steroid receptors which are translocated to the nucleus and attach to androgen response elements on DNA inducing a cassette of androgen stimulated genes that are important in cell growth and development. An unregulated growth stimulus to hepatocytes is the likely cause of nodular regeneration and hepatic tumors related to anabolic steroid use. The cause of cholestasis due to the C-17 substituted androgens is not well defined, but high doses cause a similar cholestasis in some animal models. The syndrome is similar to cholestasis of pregnancy and the jaundice associated with high doses of estrogens or birth control pills and may be due to partial lack or variant of bile salt transporter proteins.
Outcome and Management
The severity of liver injury due to anabolic steroids ranges from minor, transient serum enzyme elevations to profound and prolonged cholestasis, as well as hepatic peliosis and benign and malignant liver tumors. The first priority in management should be stopping the androgenic steroid. Unfortunately, athletes and body builders may resist this recommendation. Merely decreasing the dose of androgenic steroid or switching to another formulation is not appropriate and should be specifically discouraged. Patients being treated for hypogonadism may be switched to an unmodified form of testosterone, given by injection or cutaneous patch. Patients with marked cholestasis may be benefitted by symptomatic therapy of pruritus and fat soluble vitamin supplementation. Ursodiol is often used in drug induced cholestasis, but is efficacy has never been shown in a controlled prospective manner. Use of corticosteroids is usually ineffective and should be avoided. The syndrome is usually reversable with stopping therapy, but recovery is often protracted. In addition, fatalities have been reported, usually due to marked cholestasis complicated by malnutrition, renal failure and associated opportunitistic infections.
Representative androgenic steroids include the following: danazol, fluoxymesterone, methandienone, methenolone, methyltestosterone, nandrolone, norethandrolone, oxandrolone, oxymetholone, stanozolol, testosterone (cypionate, enanthate, propionate).
Drug Class: Anabolic Steroids
Case Report
Anabolic Steroids
Case 1. Cholestasis due to anabolic steroid use.
[Modified from: Singh C, Bishop P, Wilson R. Extreme hyperbilirubinemia associated with the use of anabolic steroids, health/nutritional supplements and ethanol: response to ursodeoxycholic acid treatment. Am J Gastroenterol 1996; 91: 783-5. PubMed Citation (http://www.ncbi.nlm.nih.gov/pubmed/8677950)]
A 24 year old body builder developed pruritus and jaundice having taken various anabolic steroids for one and a half years. He was also taking several herbal products and dietary supplements including Ma Huang (6% ephedrine), carnitine and chromium. He also drank alcohol, estimating his average intake as one case of beer per day for the last year. He developed dark urine and jaundice and stopped all medications and his alcohol intake promptly. Despite this, he remained jaundiced for a month and had worsening nausea and weight loss and eventually sought medical care. He had no history of liver disease or risk factors for viral hepatitis and took no other medications. On examination, he was muscular and physically fit but deeply jaundiced. He had an enlarged liver but no rash, fever or splenomegaly. Laboratory testing showed a total serum bilirubin of 53 mg/dL, but only modest elevations in serum aminotransferase and a normal alkaline phosphatase level (Table). His prothrombin time was normal. Tests for hepatitis A, B and C were negative. Abdominal ultrasound showed no evidence of biliary obstruction. Liver biopsy was not done. He was treated symptomatically for pruritus with antihistamines, cholestryamine and ursodiol. His jaundice gradually improved and pruritus waned. Six months after the onset of jaundice, he was asymptomatic, had regained most of his weight loss (40 pounds), serum bilirubin was 1.5 mg/dL and serum enzymes were normal.
Key Points
Medication:
Anabolic steroids (nandrolone, stanozolol)
Pattern:
Bland cholestasis
Severity:
3+ (jaundice, hospitalization)
Latency:
16 months
Recovery:
0.6 months
Other medications:
Various herbal products and dietary supplements
Laboratory Values
Time After Stopping
ALT
(U/L)
Alk P
(U/L)
Bilirubin
(mg/dL)
Other
Anabolic agent use for ~1.5 years
6 weeks
237
129
21
8 weeks
90
121
53
10 weeks
203
91
51
Ursodiol started
12 weeks
119
81
22
14 weeks
116
67
8
4 months
58
50
4
5 months
33
75
1.5
Asymptomatic
Normal Values
<56
<139
<1.2
Comment
A very typical case of severe cholestasis due to anabolic steroid use. Because the steroids were being used without medical supervision, the dose and actual duration of use of each preparation was unclear, but cholestasis usually arises within 4 to 12 weeks of starting a C-17 alkylated androgenic steroid. The jaundice can be severe and prolonged and accompanied by severe pruritus and marked weight loss. The serum enzymes are typically minimally elevated except for a short period immediately after stopping therapy. The pattern of enzyme elevations can be hepatocellular, cholestatic or mixed. Liver biopsy shows a ?bland? cholestasis with minimal inflammation and hepatocellular necrosis. Ma Huang has also been implicated in cases of drug induced liver injury, but is associated with an acute hepatocellular pattern of injury.