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 Supervisor, 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.
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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]
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.
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PRODUCT INFORMATION
Anabolic Steroids
REPRESENTATIVE TRADE NAMES
Danazol ? Generic, Danocrine?
Fluoxymesterone ? Androxy?
Methandienone ? Dianabol?
Methenolone ? Primobolan?
Methyltestosterone ? Android?, Methitest?, Testred?
Nandrolone ? Generic, Deca-Durabolin?
Norethandrolone ? Generic, Nilevar?, Norlutin?
Oxandrolone ? Generic, Oxandrin?
Oxymetholone ? Anadrol?
Stanozolol ? Winstrol?
Testosterone ? Depo-Testosterone?
DRUG CLASS
Anabolic Steroids
COMPLETE LABELING
FDA product labeling at DailyMed, National Library of Medicine, NIH
REFERENCES
Anabolic Steroids
References Last Updated: 04 September 2013
Zimmerman HJ. Hormonal derivatives and related drugs. In, Zimmerman HJ. Hepatotoxicity: the adverse effects of drugs and other chemicals on the liver. 2nd ed. Philadelphia: Lippincott, 1999, pp. 555-88. (Expert review of effects of androgenic steroids on the liver published in 1999; two forms of hepatic injury occur with anabolic steroids: cholestasis that occurs within the first 6 months associated with the synthetic agents that have an alkyl group in the C17 position, and a delayed injury with vascular or neoplastic changes in which natural androgens can play a role).
Chitturi S, Farrell GC. Adverse effects of hormones and hormone antagonists on the liver. In, Kaplowitz N, DeLeve LD, eds. Drug-induced liver disease. 3rd ed. Amsterdam: Elsevier, 2013, pp. 605-20. (Review of hepatotoxicity of androgenic steroids including cholestasis, vascular disorders, benign tumors and hepatocellular carcinoma).
Synder P. Androgens. In, Brunton LL, Chabner BA, Knollman BC, eds. Goodman & Gilman's the pharmacological basis of therapeutics. 12th ed. New York: McGraw-Hill, 2011, pp.1195-1208. (Textbook of pharmacology and therapeutics).
Werner SC, Hanger FM, Kritzler RA. Jaundice during methyltestosterone therapy. Am J Med 1950; 8: 325-31. PubMed Citation (7 patients: 6 men and 1 woman who developed jaundice during oral methyltestosterone therapy, ages 17-67 years, onset after 8 days to 4 months, prodrome of nausea and malaise for 1-2 weeks before jaundice [peak bilirubin 5.1-29 mg/dL, Alk P 1.4 to 4.5 times ULN, albumin normal], lasted 1-3 months; biopsy showed bile stasis with little inflammation; recovery complete; no recurrence upon rechallenge in 3 patients).
Brick IB, Kyle LH. Jaundice of hepatic origin during the course of methyltestosterone therapy. N Engl J Med 1952; 246: 176-9.PubMed Citation (Two men, ages 44 and 63 years, developed jaundice 7 and 12 weeks after switching from long term testosterone injections to sublingual methyltestosterone [bilirubin not given and 6.8 mg/dL, Alk P 4-5 times ULN], with full but slow recovery after stopping).
Burger RA, Marcuse PM. Peliosis hepatis: report of a case. Am J Clin Pathol 1952; 22: 569-73. PubMed Citation (39 year old woman with metastatic colon cancer and emaciation treated with oral testosterone was found to have peliosis hepatis on autopsy, without endothelial lining and with hepatic necrosis).
Lloyd-Thomas HG, Sherlock S. Testosterone therapy for the pruritus of obstructive jaundice. Br Med J 1952; 2: 1289-91. PubMed Citation (Experience in treating 7 patients having intractable itching due to liver disease with methyltestosterone, which led to improvement in itching within 4-7 days but worsening jaundice, serum bilirubin rising by 2.0-9.3 mg/dL).
Almaden PJ, Ross SW. Jaundice due to methyl testosterone therapy. Ann Intern Med 1954; 40: 146-52. PubMed Citation (45 year old woman developed jaundice 7 months after starting methyltestosterone [bilirubin 16.7 mg/dL Alk P slightly elevated], biopsy showing intrahepatic cholestasis and resolution of jaundice within 2 months of stopping).
Kaplan AA. Jaundice due to methyltestosterone therapy. Gastroenterology 1956; 31: 384-90. PubMed Citation (58 year old man developed jaundice and pruritus 6 months after starting sublingual methyltestosterone [bilirubin 13.6 mg/dL, Alk P rising to twice normal], resolving 3 months after stopping).
Koszalka MF. Medical obstructive jaundice: report of a death due to methyltestosterone. J Lancet 1957; 77: 51-4. PubMed Citation(60 year old man with colon cancer developed jaundice 3 weeks after starting methyltestosterone which was continued another 3 weeks [bilirubin 10 mg/dL, Alk P rising to twice normal], with progressive jaundice and death from hepatic failure 2 months after presentation, autopsy showing intrahepatic cholestasis).
Peters JH, Randall AH Jr, Mendeloff J, Peace R, Coberly JC, Hurley MB. Jaundice during administration of methylestrenolone. J Clin Endocrinol 1958; 18: 114-5. PubMed Citation (Two of 10 patients receiving 17-methyl-19-nortestosterone for cancer developed jaundice after 4 and 6 weeks of therapy; both died of underlying cancer while still jaundiced).
Seelen JC. Complications during administration of methylestrenolone. J Clin Endocrinol 1958; 1137-8. PubMed Citation (Pregnant woman treated with methylestrenolone for habitual abortion developed jaundice 2 months later [bilirubin 19 mg/dL, Alk P 1.5 times ULN], resolving after stopping therapy).
Kory RC, Bradley MH, Watson RN, Callahan R, Peters BJ. A six-month evaluation of an anabolic drug, norethandrolone, in underweight persons. II. Bromsulphalein(BSP) retention and liver function. Am J Med 1959; 26: 243-8. PubMed Citation(Prolonged BSP retention found in 74% of samples from 47 patients on norethandrolone for weight gain, returned to normal within a few weeks of stopping; only two patients had mild bilirubin elevations [1.7 and 2.2 mg/dL]).
Schaffner F, Popper H, Chesrow E. Cholestasis produced by administration of norethandrolone. Am J Med 1959; 26: 249-54.PubMed Citation (Among 27 patients treated with norethandrolone for nutritional support for 3 to 5 weeks undergoing liver biopsy before and during therapy, 4 developed cholestasis within 1 to 5 weeks [bilirubin 32, 1.8, 1.0 and 0.7 mg/dL, AST 190-224 U/L, Alk P 2-20 times ULN], all resolving after stopping).
Foss GL, Simpson SL. Oral methyltestosterone and jaundice. Br Med J 1959; 1 : 259-63. PubMed Citation (Despite extensive use of methyltestosterone, authors found only one case of jaundice, 60 year old man developed jaundice after 5 weeks of therapy and subsequently died of dehydration and acidosis; summarizes 42 cases from literature; of 5 patients retreated, only one had recurrence).
Shaw RK, Gold GL. Jaundice associated with norethandrolone(Nilevar) therapy. Ann Intern Med 1960; 52: 428-34. PubMed Citation(60 year old with multiple myeloma developed pruritus after 12 weeks and jaundice after 16 weeks of norethandrolone [bilirubin 9.5 mg/dL, AST 25 U/L, Alk P 3 times ULN], biopsy showed intrahepatic cholestasis, resolving on stopping and prednisone therapy).
Wernze H. [Clinical investigation of the problem of liver damage by the newer androgenic and anabolic steroids]. Dtsch med Wschr 1960; 85: 2237-42. German.PubMed Citation (Study of BSP retention in 36 volunteers given C-17 alkylated androgenic steroids; retention rose from <5% to 6-23% within 8-30 days and fell to normal or near normal with 8-10 days thereafter, whereas AST, Alk P and bilirubin levels changed minimally if at all).
Kintzen W, Silny J. Peliosis hepatic after administration of fluoxymesterone. Can Med Assoc J 1960; 83: 860-2. PubMed Citation(60 year old woman with metastatic breast cancer treated with fluoxymesterone for 2 years was found to have peliosis hepatis on autopsy after death from widespread metastatic disease).
Schaffner F, Popper H, Perez V. Changes in bile canaliculi produced by norethandrolone: electron microscopic study of human and rat liver. J Lab Clin Med 1960; 56: 623-8. PubMed Citation (4 patients treated with norethandrolone for 2 weeks underwent liver biopsy which showed ?mild nonspecific changes? by light microscopy, but dilated bile canaliculi and shortening of microvilli by electron microscopy).
Marquardt GH, Fisher CI, Levy P, Dowben RM. Effects of anabolic steroids on liver function tests and creatine excretion. JAMA 1961; 175: 851-3. PubMed Citation (Six anabolic steroids given to 38 healthy controls for 5 weeks; all led to increase in BSP retention [2.3-17.6%] but no change in bilirubin levels).
Wynn V, Landon J, Kawarau E. Studies of hepatic function during methandienone therapy. Lancet 1961; 1: 69-75. PubMed Citation(Followed liver tests in 30 patients treated with methandienone; AST elevations occurred in 27% [60-180 U/L], Alk P(2 times ULN] and bilirubin [2.0] in 1, and BSP retention in 62%; all without symptoms and resolving rapidly, some without stopping drug).
Perez-Mera RA, Shields CE. Jaundice associated with norethindrone acetate therapy. N Engl J Med 1962; 267: 1137-8. PubMed Citation (35 year old woman developed jaundice and abdominal pain 2 years after starting norethindrone for dysmenorrhea [bilirubin 6.5 mg/dL], biopsy showing intrahepatic cholestasis and repeat biopsy 2 months after stopping estrogen showing resolution).
Wilder EM. Death due to liver failure following the use of methandrostenolone. Can Med Assoc J 1962; 87: 768-9. PubMed Citation(71 year old woman developed jaundice 8 weeks after starting methandrostenolone for osteoporosis [bilirubin 20.4 mg/dL, AST 200 U/L, Alk P twice normal], with progressive mental obtundation, coagulopathy and death 2 months later, autopsy showing shrunken liver with marked cholestasis).
Scherb J, Kirschner M, Arias IM. Studies of hepatic excretory function. The effect of 17α-ethyl-19-nortestosterone on sulfobromophthalein sodium(BSP) metabolism in man. J Clin Invest 1963: 42: 404-8. PubMed Citation (Prospective study of BSP metabolism in 8 subjects treated with 19-nortestosterone and 10 controls; BSP transport maximum decreased within 7-10 days of starting androgen therapy and returned to normal 1 week afterwards, BSP storage was normal; best explained as a decrease in excretion of conjugated BSP [similar to defect in Dubin-Johnson syndrome).
Gilbert EF, DaSilva AQ, Queen DM. Intrahepatic cholestasis with fatal termination following norethandrolone therapy. JAMA 1963; 185: 538-9. PubMed Citation (74 year old man developed jaundice 5 months after starting norethandrolone but continued for another month and developed delirium [bilirubin 20 mg/dL, AST 475 U/L, Alk P 3 times ULN], dying in hepatic coma; severe cholestasis on autopsy).
Marquardt GH, Logan CE, Tomhave WG, Dowben RM. Failure of non-17-alkylated anabolic steroids to produce abnormal liver function tests. J Clin Endocrinol Metab 1964; 24: 1334-6. PubMed Citation (Prospective study of 23 patients given methenolone [non-C-17 substituted synthetic androgen] for weight gain found no change in BSP retention or serum bilirubin levels).
Yanoff M, Rawson AJ. Peliosis hepatis: an anatomic study with demonstration of two varieties. Arch Pathol 1964; 77: 159-65.PubMed Citation (Two cases: 73 year old woman with septic arthritis treated with norethandrolone for 6 weeks and 42 year old man with malignant teratoma treated with chemotherapy for 8 months, both found to have peliosis on autopsy; two forms of peliosis, one with and one without endothelial lining, anabolic steroids associated with the latter parenchymal type that also shows bile retention and hepatocyte necrosis).
DeLorimer AA, Gordan GS, Lowe RC, Carbone JV. Methyltestosterone, related steroids and liver function. Arch Intern Med 1965; 116: 289-94. PubMed Citation (66 healthy controls were given 9 different 17α-alkylated androgenic steroids or testosterone for 2 weeks; no change in serum bilirubin or Alk P, but most resulted in increased BSP retention, not occurring with non-alkylated testosterone).
Ticktin HE, Zimmerman HJ. Effects of synthetic anabolic agent on hepatic function. Am J Med Sci 1966; 251: 674-84. PubMed Citation (Prospective analysis of liver tests in 54 patients treated with nobolethone for at least 2 weeks; reversible minor AST elevations in 33% and BSP retention in 66% [both dose related], bilirubin >1.0 mg/dL in 10% and abnormal Alk P in none).
Orlandi F, Jezequel AM. On the pathogenesis of the cholestasis induced by C-17 alkylated steroids: ultrastructure and functional changes of the liver cells during treatment. Rev Int Hepatol 1966; 16: 331-3. PubMed Citation
Glober GA, Wilkerson JA. Biliary cirrhosis following the administration of methyltestosterone. JAMA 1968; 204: 170-3. PubMed Citation (56 year old woman developed jaundice after taking a nutritional supplement with methyltestosterone and estrone for 4 years with prolonged jaundice [bilirubin 3.2 mg/dL, AST 7 UL, Alk P 54 KA U], evolving into cirrhosis over next 5 years with intractable pruritus and xanthomas; probable primary biliary cirrhosis).
. Androgens and anabolic steroids. Br Med J 1969; 2: 165-7. PubMed Citation (Review of clinical indications, efficacy and safety of androgenic steroids; mentions that 17α-alkylated androgens can cause jaundice).
McGiven AR. Peliosis hepatis: case report and review of pathogenesis. J Pathol 1970; 101: 283-5. PubMed Citation (75 year old man with rheumatoid arthritis died of an acute myocardial infarction and was found to have peliosis hepatis on autopsy, having received methandienone for the previous year).
Rozman C, Urbano A, Galera H. [Hepatotoxicity of anabolic steroids]. Minerva Med 1971; 62: 2605-11. PubMed Citation
Sansoy OM, Roy AN, Shields LM. Anabolic action and side effects of oxandrolone in 34 mental patients. Geriatrics 1971; 26: 139-43. PubMed Citation (34 patients were treated with oxandrolone for 2 months to promote weight gain after illness; AST levels increased and were abnormal in 53%, BSP increased in 35%; no patient developed jaundice).
Bernstein MS, Hunter RL, Yachnin S. Hepatoma and peliosis hepatis developing in a patient with Fanconi's anemia. N Engl J Med 1971; 284: 1135-6. PubMed Citation (20 year old with Fanconi anemia developed HCC 1 year after starting oxymetholone with peliosis and multiple intrahepatic hematomas found on autopsy).
Johnson FL, Feagler JR, Lerner KG, Majerus PW, Siegel M, Hartmann JR, Thomas ED. Association of androgenic-anabolic steroid therapy with the development of hepatocellular carcinoma. Lancet 1972; 2: 1273-6. PubMed Citation (Description of 4 cases of hepatocellular carcinoma related to C17-alkylated anabolic steroids given for aplastic anemia or Fanconi syndrome, ages 5-27 years taking drugs for 1-7 years; regression of tumor in one with withdrawal; all died within one year).
Guy JT, Auslander MO. Androgenic steroids and hepatocellular carcinoma. Lancet 1973; 1: 148. PubMed Citation (38 year old man with Fanconi?s syndrome had hepatocellular carcinoma on autopsy with mildly abnormal liver tests; had received androgenic steroids for 4 months at age 14).
Henderson JT, Richmond J, Sumerling MD. Androgenic-anabolic steroid therapy and hepatocellular cancer. Lancet 1973; 1: 934.PubMed Citation (12 year old male with aplastic anemia developed hepatocellular carcinoma having received 8 years of intermittent anabolic steroid therapy and many transfusions).
. Liver tumours and steroid hormones. Lancet 1973; 2: 1481-2. PubMed Citation (Editorial discussing the development of cholestasis, peliosis, adenoma and hepatocellular carcinoma after anabolic and contraceptive steroids).
Jackson ST, Rallison ML, Buntin WH, Johnson SB, Flynn RR. Use of oxandrolone for growth stimulation in children. Am J Dis Child 1973; 126: 481-4. PubMed Citation (9 children with constitutional growth retardation treated with oxandrolone for 2 6-month periods with careful monitoring; no clinical or laboratory evidence of liver injury; one patient had increase in BSP retention).
Presant CA, Safdar SH. Oxymetholone in myelofibrosis and chronic lymphocytic leukemia. Arch Intern Med 1973; 132: 175-8.PubMed Citation (Among 9 patients with refractory anemia, oxymetholone decreased transfusion requirements; 4 developed hepatotoxicity after 3-6 months, mild jaundice in 1 [bilirubin 3.1 mg/dL], mild Alk P or AST elevations in others, most resolved despite continuing medication).
Ziegenfuss J, Carabasi R. Androgens and hepatocellular carcinoma. Lancet 1973; 1: 262. PubMed Citation (68 year old man treated with methyltestosterone for 30 years for impotence presented with abdominal pain and hepatocellular carcinoma which was ?almost completely? resected).
Frasier SD. Androgens and athletes. Am J Dis Child 1973; 125: 479-80. PubMed Citation (Editorial criticizing use of anabolic steroids to improve athletic performance).
Naeim F, Copper PH, Seminion AA. Peliosis hepatis: possible etiologic role of anabolic steroids. Arch Pathol 1973; 95: 284-5.PubMed Citation (Two cases of peliosis found on autopsy; a child with Fanconi?s anemia who had developed jaundice after a short course of fluoxymesterone; a 65 year old woman on hormone replacement therapy for 18 months who died of congestive heart failure).
Bagheri SA, Boyer JL. Peliosis hepatis associated with androgenic-anabolic steroid therapy. A severe form of hepatic injury. Ann Intern Med 1974; 81: 610-8. PubMed Citation (Seven patients on anabolic steroids for 2 to 27 months developed peliosis, 2 developing hemorrhage, 3 hepatic failure and 2 renal failure; serum bilirubin levels as high as 34.6 mg/dL, Alk P 1-20 times elevated, AST 30 to 950 U/L).
Groos G, Arnold OH, Brittinger G. Letter: Peliosis hepatis after long-term administration of oxymetholone. Lancet 1974; 1: 874.PubMed Citation (33 year old woman with aplastic anemia developed hepatomegaly [bilirubin 6.6 mg//dL, ALT 243 U/L, Alk P 229 U/L] 1.5 years after starting oxymetholone, liver size decreasing when drug was stopped).
Cattan D, Vesin P, Wautier J, Kalifat R, Meignan S. Liver tumors and steroid hormones. Lancet 1974; 1: 878. PubMed Citation (7 year old girl with Fanconi?s anemia developed hepatocellular carcinoma but had never received androgenic steroids, instead had transfusion-attributed hemosiderosis and cirrhosis).
Meadows AT, Naiman JL, Valdes-Dapena MV. Hepatoma associated with androgen therapy for aplastic anemia. J Pediatr 1974; 84: 109-10. PubMed Citation (6 year old girl with aplastic anemia on androgens for 3.5 years died of intracranial hemorrhage and was found to have hepatocellular carcinoma on autopsy; the liver was enlarged but liver tests were all normal).
Mulvihill JJ, Ridolfi RL, Schultz FR, Borzy MS, Haughton PB. Hepatic adenoma in Fanconi anemia treated with oxymetholone. J Pediatr 1975; 87: 122-4. PubMed Citation (12 year old boy with Fanconi?s anemia treated with oxymetholone developed jaundice [bilirubin 23 mg/dL and ?liver function abnormalities?], improving when oxymetholone was stopped; on autopsy after intracerebral bleed found to have 9 cm hepatic adenoma ?with distant metastases?).
Sarna G, Tomasulo P, Lotz MJ, Bubinak JF, Shulman NR. Multiple neoplasms in two siblings with a variant form of Fanconi's anemia. Cancer 1975; 36: 1029-33. PubMed Citation (Two brothers with Fanconi?s anemia on long term androgen therapy both developed malignancies, including leukemia, gingival squamous cell cancer, and hepatocellular carcinoma).
K?hb?ck J, Radaszkiewicz T, Walek H. [Peliosis hepatis, complicating treatment with anabolic steroids (author's transl)]. Med Klin 1975; 70: 1602-7. German. PubMed Citation
Ball JH, Lowrie EG, Hampers CL, Merrill JP. Testosterone therapy in hemodialysis patients. Clin Nephrol 1975; 4: 91-8. PubMed Citation (30 patients on chronic hemodialysis were treated with testosterone injections for anemia; AST elevations occurred in both treated and untreated controls).
Farrell GC, Joshua DE, Uren RF, Baird PJ, Perkins KW, Kronenberg. Androgen-induced hepatoma. Lancet 1975; 1: 430-1. PubMed Citation (Three cases of hepatocellular carcinoma in men on androgenic steroids, ages 28 to 40 years, on oxymetholone or methyltestosterone for 5 to 8 years, liver and tumor size decreasing on stopping androgenic steroids).
Anthony PP. Hepatoma associated with androgenic steroids. Lancet 1975; 1: 685-6.PubMed Citation (Letter in response to Farrell [1975] stressing the poor prognosis of hepatocellular carcinoma; median survival time being 1 month and raising a question of the accuracy of the diagnosis).
Bakker K, Brouwers TM, Houthoff HJ, Postma A. [Liver lesions due to long-term use of anabolic steroids and oral contraceptives]. Ned Tijdschr Geneeskd 1976; 120: 2214-20. Dutch. PubMed Citation
Kew MC, Van Coller B, Prowse CM, Skikne B, Wolfsdorf JI, Isdale J, Krawitz S, et al. Occurrence of primary hepatocellular cancer and peliosis hepatis after treatment with androgenic steroids. S Afr Med J 1976; 50: 1233-7. PubMed Citation (3 cases of complications of androgenic steriods: 34 year old woman with Fanconi?s anemia developed hepatocellular carcinoma after 7 years of therapy with methyltestosterone and 2 children [1 girl and 1 boy] developed peliosis hepatis, 5 and 8 years after starting androgenic steroids, both died soon after diagnosis).
Kessler E, Bar-Meir S, Pinkhas J. [Focal nodular hyperplasia and spontaneous hepatic rupture in aplastic anemia treated with oxymetholone]. Harefuah 1976; 90: 521-4. Hebrew. PubMed Citation
Boyer JL, Preisig R, Zbinden G, de Kretser DM, Wang C, Paulsen CA. Guidelines for assessment of potential hepatotoxic effects of synthetic androgens, anabolic agents and progestagens in their use in males as antifertility agents. Contraception 1976; 13: 461-8. PubMed Citation (Recommendations for monitoring for hepatotoxicity in trials of anabolic steroids).
Hast R, Sk?rberg KO, Engstedt L, Jameson S, Killander A, Lundh B, Reizenstein P, et al. Oxymetholone treatment in aregenerative anaemia. II. Remission and survival?a prospective study. Scand J Haematol 1976; 16: 90-100. PubMed Citation (53 patients with anemia due to bone marrow insufficiency were treated with oxymetholone for at least 6 months; 3 developed jaundice requiring discontinuation).
Hervey GR, Hutchinson I, Knibbs AV, Burkinshaw L, Jones PR, Norgan NG, Levell MJ. "Anabolic" effects of methandienone in men undergoing athletic training. Lancet 1976; 2: 699-702. PubMed Citation (Double-blind crossover study of 6 weeks of methandienone in 11 male athletes; no change in bilirubin, ALT, AST or Alk P levels during drug period).
Lesna M, Spencer I, Walker W. Liver nodules and androgens. Lancet 1976; 1: 1124.PubMed Citation (17 year old male with long standing aplastic anemia treated with oxymetholone developed sudden rupture of right lobe of liver and autopsy revealed multiple hepatic nodules and adenomas).
Slater SD, Davidson JF, Patrick RS. Jaundice induced by stanozolol hypersensitivity. Postgrad Med J 1976; 52: 229-32. PubMed Citation (66 year old man developed jaundice 7 months after starting stanozol [bilirubin 8.0 mg/dL, ALT 74 U/L, Alk P 3 times ULN], with biopsy showing cholestasis but conspicuous eosinophils suggesting ?hypersensitivity? with slow resolution over ensuing 6 months).
Sweeney EC, Evans DJ. Hepatic lesions in patients treated with synthetic anabolic steroids. J Clin Pathol 1976; 29: 626-33.PubMed Citation (Three cases of liver injury due to anabolic steroids; 8 year old boy with Fanconi?s syndrome developed hepatocellular carcinoma after 3 years of methyltestosterone therapy; 46 year old man with severe, ultimately fatal cholestasis [bilirubin 9.8 mg/dL, AST 102 U/L, Alk P 1510 U/L] 3 months after starting oxymetholone; 31 year old woman with aplastic anemia died of intracerebral bleeding after 3 months of oxymetholone therapy and had regenerative hepatic nodules on autopsy).
Tso SC, Chan TK, Todd D. Aplastic anaemia: a study of prognosis and the effect of androgen therapy. Q J Med 1977; 46: 513-29.PubMed Citation (129 cases of aplastic anemia from Hong Kong between 1955-74; 75 received androgen therapy, among whom 12 [16%] had ALT elevations, 7 [10%] jaundice and 2 died with persistent jaundice).
Young GP, Bhathal PS, Sullivan JR, Wall AJ, Fone DJ, Hurley TH. Fatal hepatic coma complicating oxymetholone therapy in multiple myeloma. Aust NZ J Med 1977; 7: 47-51.PubMed Citation (Two patients, 56 year old woman and 60 year old man developed severe jaundice 6 and 8 weeks after starting oxymetholone for multiple myeloma [bilirubin 11.7 and 21.9 mg/dL, AST normal, Alk P 286 and 700 U/L], with progressive jaundice, renal failure, hepatic encephalopathy and death within 4-6 weeks of presentation).
Leong AS, Sage RE. Drug-induced hepatic injury. Aust N Z J Med 1977; 7: 537-9.PubMed Citation (Letter in response to Young [1977] describing 76 year old woman who developed jaundice while receiving oxymetholone and was continued for 3 months [bilirubin 6.2 mg/dL, ALT 346 U/L, Alk P 116 U/L], followed by hepatic failure but biopsy showed marked cholestasis with little necrosis).
Bhathal PS, Fone DJ, Hurley TH, Sullivan JR, Wall AJ, Young GP. Drug-induced hepatic injury. Aust N Z J Med 1977; 7: 539-40.PubMed Citation (Reply to Leong and Sage [1977]; retrospective review of 27 patients with multiple myeloma treated with oxymetholone identified 9 [47%] who developed jaundice).
Nadell J, Kosek J. Peliosis hepatis. Twelve cases associated with oral androgen therapy. Arch Pathol Lab Med 1977; 101: 405-10.PubMed Citation (12 patients with peliosis who had received oral androgens for 3 to 24 months from a single institution; 3 died of hepatic failure related to peliosis, one had diagnosis by biopsy and peliosis resolved with stopping androgens, 8 others found incidentally on autopsy; also reviewed 42 cases of peliosis in English literature).
Bird DR, Vowles KDJ. Liver damage from long-term methyltestosterone. Lancet 1977; 2: 400-1. PubMed Citation (39 year old transsexual treated with methyltestosterone for 7 years developed sudden hepatic rupture due to peliosis hepatis).
Westaby D, Ogle SJ, Paradinas FJ, RandellJB, Murray-Lyon IM. Liver damage from long-term methyltestosterone. Lancet 1977; 2: 261-3. PubMed Citation (Among 60 patients on long term methyltestosterone, 32% had raised AST, 55% abnormal liver scan; liver biopsies in 11 showed sinusoidal dilatation in 9 and cholestasis in 3 [one with bilirubin of 1.7 mg/dL] and one developed adenoma).
Mokrohinsky TS, Ambruso DR, Hathaway WE. Fulminant hepatic neoplasia after androgen therapy. N Engl J Med 1977; 296: 1411-2. PubMed Citation (6 year old girl with Fanconi?s anemia developed hepatomegaly 2 months after starting oxymetholone with hepatocellular carcinoma in a noncirrhotic liver, dying 5 weeks after diagnosis).
Boyd PR, Mark GJ. Multiple hepatic adenomas and a hepatocellular carcinoma in a man on oral methyl testosterone for 11 years. Cancer 1977; 40: 1765-70. PubMed Citation (29 year old man developed multiple hepatic adenomas and hepatocellular carcinoma 12 years after starting oral methyltestosterone for hypopituitarism).
Sale GE, Lerner KG. Multiple tumors after androgen therapy. Arch Pathol Lab Med 1977; 101: 600-3. PubMed Citation (37 year old man with aplastic anemia developed hepatocellular carcinoma and peliosis hepatis as well as pancreatic and renal tumors after 5 years of anabolic steroid therapy).
Hernandez-Nieto L, Bruguera M, Bombi J, Camacho L, Rozman C. Benign liver-cell adenoma associated with long-term administration of an androgenic-anabolic steroid(methandienone). Cancer 1977; 40: 1761-4. PubMed Citation (19 year old man presented with two hepatic adenomas, one of which ruptured after 3 years of methandienone therapy for paroxysmal nocturnal hemoglobinuria).
Paradinas FJ, Bull TB, Westaby D, Murray-Lyon IM. Hyperplasia and prolapse of hepatocytes into hepatic veins during longterm methyltestosterone therapy: possible relationships of these changes to the development of peliosis hepatis and liver tumours. Histopathology 1977; 1: 225-46. PubMed Citation (Liver histology from 11 patients treated with methyltestosterone for up to 3 years [ALT abnormal in 6 patients, range 53-246 U/L], found sinusoidal dilatation in most cases and ?microcysts? with hyperplasia of hepatocytes that partially occluded the sinusoidal or hepatic vein lumens).
Shapiro P, Ikeda RM, Ruebner BH, Connors MH, Halsted CC, Abildgaard CF. Multiple hepatic tumors and peliosis hepatis in Fanconi's anemia treated with androgens. Am J Dis Child 1977; 131: 1104-6. PubMed Citation (13 year old boy with Fanconi?s anemia, who was treated with oxymetholone for 5-6 years, died of septicemia and was found to have hepatocellular carcinoma and peliosis hepatis on autopsy).
Coombes GB, Reiser J, Paradinas FJ, Burn I. An androgen-associated hepatic adenoma in a trans-sexual. Br J Surg 1978; 65: 869-70. PubMed Citation (27 year old woman transsexual treated with methyltestosterone for 3 years presented with abdominal pain