Anabolic Steroids & Liver [GI]

Variation in Phase II Metabolism of Sex Steroids - Causes and Consequences

Eight articles are included in this Research Topic, of which three are reviews and five are original research articles.

Phase II metabolism, usually known as conjugation reactions, generate metabolites that are, in most cases, biologically inactive and subsequently excreted in bile or urine.

Androgenic and estrogenic sex steroids are mainly inactivated by sulfation or glucuronidation by the enzyme families sulfotransferases (SULTs) or uridine diphospho glucuronosyltransferases (UGTs).

This reaction step has been suggested to play an important role in regulating the intracellular levels of unconjugated steroids and their biological activity in tissues.

Variation in expression and activity in these sex-steroid conjugating enzymes have been implicated to

• play a role in numerous hormone dependent diseases, such as several types of cancer, PCOS, metabolic syndrome and osteoporosis
• impact therapeutic response to hormone related drugs including drug abuse (such as anabolic androgenic steroids)
• distort the analysis results of certain drug tests

The inter-individual variation is to a large extent due to genetic polymorphisms that changes the expression or activity of the enzyme. Other important factors are environment and diet that may have a direct impact and/or will affect the epigenome, i.e. the transcription of these genes. In addition variation between males and females has been shown in activity and mRNA expression for some of these enzymes.

The aim of this research topic forum is to highlight the progress made in this field via review papers and original articles as well as to promote future research with the aim to further understand the consequences of inter-individual difference in phase II metabolism and regulation of sex steroids.

Schulze JJ, Ekstrom L. Editorial: Variation in Phase II Metabolism of Sex Steroids - Causes and Consequences. Front Endocrinol (Lausanne). 2015;6:50. http://journal.frontiersin.org/article/10.3389/fendo.2015.00050/full
 
Solbach P, Potthoff A, Raatschen HJ, Soudah B, Lehmann U, et al. Testosterone-receptor positive hepatocellular carcinoma in a 29-year old bodybuilder with a history of anabolic androgenic steroid abuse: a case report. BMC Gastroenterol. 2015;15(1):60. http://www.ncbi.nlm.nih.gov/pubmed/25986067

BACKGROUND: Continuous use of anabolic androgenic steroid in high-doses is associated with substantial health risks, including hepatocellular adenoma.

Malignant transformation from hepatocellular adenoma to hepatocellular carcinoma after anabolic androgenic steroid abuse has been rarely reported.

The morphological distinction of adenoma from well-differentiated hepatocellular carcinoma is challenging and requires elaborated imaging techniques and histology.

CASE PRESENTATION: We report about a 29-year old male professional bodybuilder who presented with mid-epigastric pain at the emergency unit.

Ultrasound showed a severe hepatomegaly with multiple lesions. Contrast-enhanced ultrasound revealed a heterogeneous pattern with signs of hepatocellular carcinoma. CT scan of the abdomen confirmed multiple hypervascular lesions and central areas of necrosis without contrast enhancement.

Subsequent diagnostics included fine needle aspiration (FNA) of suspicious lesions and mini-laparoscopy to establish the diagnosis of a beta-catenin and testosterone-receptor positive hepatocellular carcinoma embedded in multiple adenomas.

The patient was subsequently treated by liver transplantation and remains tumor-free 27 month after surgery.

CONCLUSION: Hepatocellular carcinoma occurring in association with anabolic androgenic steroid abuse should sensitize physicians and especially professional bodybuilders for the harmful use of high doses of steroids.
 
@Michael Scally MD

Is this related to use of compounds both in orals or injectable form like: winstrol-Dianabol-anadrol-halotestin or even injectable steroids like deca-tren-eq-masteron can give hepatocellular carcinoma?
 
Padda MS, Sanchez M, Akhtar AJ, Boyer JL. Drug-induced cholestasis. Hepatology. 2011;53(4):1377-87. http://onlinelibrary.wiley.com/doi/10.1002/hep.24229/full

Recent progress in understanding the molecular mechanisms of bile formation and cholestasis have led to new insights into the pathogenesis of drug-induced cholestasis. This review summarizes their variable clinical presentations, examines the role of transport proteins in hepatic drug clearance and toxicity, and addresses the increasing importance of genetic determinants, as well as practical aspects of diagnosis and management.
 
Li Y, Liu L, Wang B, Chen D, Wang J. Nonalcoholic fatty liver disease and alteration in semen quality and reproductive hormones. Eur J Gastroenterol Hepatol. http://journals.lww.com/eurojgh/Abs...ty_liver_disease_and_alteration_in.98696.aspx

OBJECTIVES: Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the world. Some reports have shown that NAFLD may cause multisystem damage, but its influence on male reproductive function has rarely been studied. AIM: To evaluate the influence of NAFLD on sperm quality and reproductive hormones in Chinese men.

MATERIALS AND METHODS: A total of 102 NAFLD men and 94 healthy men without fatty liver (control) were enrolled in this study. All participants underwent a physical examination, and were subjected to lifestyle questionnaires and abdominal ultrasound examination. The semen quality (volume, concentration, motility, and morphology) and serum hormonal levels (testosterone, estradiol, follicle-stimulating hormone, inhibin B, sex hormone-binding globulin, and luteinizing hormone) were examined and compared between the two groups.

RESULTS: The levels of serum testosterone and sex hormone-binding globulin were significantly lower in the NAFLD patients compared with the control group. Sperm concentration (P=0.04), sperm count (P=0.01), and total motility (P=0.03) in the NAFLD patients were significantly decreased compared with the control group. However, no significant differences were observed in semen volume and morphology. Multivariate analysis showed that sperm concentration, sperm count, and motility were significantly associated with NAFLD and abstinence (P<0.05 or P<0.001).

CONCLUSION: These results suggest that NAFLD could significantly affect sperm quality and reproductive hormones.
 
Li Y, Liu L, Wang B, Chen D, Wang J. Nonalcoholic fatty liver disease and alteration in semen quality and reproductive hormones. Eur J Gastroenterol Hepatol. http://journals.lww.com/eurojgh/Abs...ty_liver_disease_and_alteration_in.98696.aspx

OBJECTIVES: Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the world. Some reports have shown that NAFLD may cause multisystem damage, but its influence on male reproductive function has rarely been studied. AIM: To evaluate the influence of NAFLD on sperm quality and reproductive hormones in Chinese men.

MATERIALS AND METHODS: A total of 102 NAFLD men and 94 healthy men without fatty liver (control) were enrolled in this study. All participants underwent a physical examination, and were subjected to lifestyle questionnaires and abdominal ultrasound examination. The semen quality (volume, concentration, motility, and morphology) and serum hormonal levels (testosterone, estradiol, follicle-stimulating hormone, inhibin B, sex hormone-binding globulin, and luteinizing hormone) were examined and compared between the two groups.

RESULTS: The levels of serum testosterone and sex hormone-binding globulin were significantly lower in the NAFLD patients compared with the control group. Sperm concentration (P=0.04), sperm count (P=0.01), and total motility (P=0.03) in the NAFLD patients were significantly decreased compared with the control group. However, no significant differences were observed in semen volume and morphology. Multivariate analysis showed that sperm concentration, sperm count, and motility were significantly associated with NAFLD and abstinence (P<0.05 or P<0.001).

CONCLUSION: These results suggest that NAFLD could significantly affect sperm quality and reproductive hormones.
 
Nadimi A, Nasseri A, Nikookheslat S. Effects of resistance exercise and the use of anabolic androgenic steroids on hemodynamic characteristics and muscle damage markers in bodybuilders. J Sports Med Phys Fitness. http://www.minervamedica.it/en/jour...al-fitness/article.php?cod=R40Y9999N00A150097

AIM: Anabolic androgenic steroids (AAS), synthetic compounds of testosterone commonly used as sport performance enhancers, could cause cardiovascular dysfunction and cell damage. Even though the side effects of AAS intake have been widely studied, yet little is known about how resistance exercise can alter these side effects.

This study aimed to determine the effects of one session resistance exercise and the use of AAS on hemodynamic characteristics and muscle damage markers in professional bodybuilders.

METHODS: Sixteen bodybuilders were divided into two groups: bodybuilders using AAS for at least 5 years (users;; n = 8) and AAS--free bodybuilders (non--users;; n = 8).

The exercise protocol was a circuit strength training session involved three sets of 8--9 repetitions at 80--85% of 1--RM.

Heart rate (HR), blood pressure (BP) and concentrations of serum creatine kinase (CK) and lactate dehydrogenase (LDH) were measured at three different time points, immediately before and after the exercise session and 24--h following the exercise session.

RESULTS: The users group showed greater basal levels of hemodynamic characteristics (i.e. HR and BP) and cell damage markers (i.e. CK and LDH) compared to those in the non--users group (all P < 0.05).

Furthermore, the exercise session significantly increased the levels of HR ( P = 0.02) and CK ( P = 0.01) in the users group compared to those in the non--users group immediately after the exercise. No significant differences were observed in BP and LDH responses to exercise between the users and the non--users groups ( P > 0.05).

CONCLUSIONS: These findings indicate that the use of AAS could be potentially harmful as it enhances the levels of the hemodynamic characteristics and the muscle enzymes. These harmful effects of AAS intake could be more evident in response to resistance exercise.
 
Brazeau MJ, Castaneda JL, Huitron SS, Wang J. A Case Report of Supplement-Induced Hepatitis in an Active Duty Service Member. Mil Med. 2015;180(7):e844-e6. http://publications.amsus.org/doi/abs/10.7205/MILMED-D-14-00654

The incidence of drug-induced hepatic injury has been increasing as a result of more widespread use of workout supplements containing anabolic steroids to increase muscle mass.

Synthetic androgenic steroids are shown to cause cholestatic liver injury, but the exact mechanism of injury is not completely understood.

We present a case of a healthy, young, active duty Army male soldier who developed pruritis and jaundice shortly after starting to take a body-building supplement containing anabolic steroids, and was subsequently found to have significant biopsy proven drug-induced liver injury.
 
I use oral AAS for my firsts cycles, Winny and anavar, and I have used samarin to protect my liver. I guess it did work....I still have my liver :)


"Pain is temporary, Pride is forever»
 
Mody A, White D, Kanwal F, Garcia JM. Relevance of low testosterone to nonalcoholic fatty liver disease. Cardiovascular Endocrinology.Publish Ahead of Print. http://journals.lww.com/cardiovascu...f_low_testosterone_to_nonalcoholic.99932.aspx

Nonalcoholic fatty liver disease (NAFLD) is a condition where there is excess accumulation of triglycerides in the liver in the absence of excess alcohol consumption. It ranges from simple steatosis to nonalcoholic steatohepatitis, which can progress to fibrosis, cirrhosis, and hepatocellular carcinoma.

NAFLD, one of the most common causes of chronic liver disease in Western populations, is the hepatic component of the metabolic syndrome and is associated with increased visceral adipose tissue (VAT), insulin resistance, and dyslipidemia.

Studies have also shown that testosterone deficiency is associated with increased VAT and insulin resistance in men, whereas hyperandrogenemia has been associated with increased risk of insulin resistance and VAT in women.

Thus, the aims of this review are to discuss the available experimental and epidemiological data evaluating the association between testosterone and NAFLD, to discuss the potential clinical relevance of these data, and to identify gaps in the literature.
 
I had hepatitis when i was in my late 20's,i am now 68 and just had the hepatitis test done.I thought that once you got it you had it for life but my results show negative.I was in isolation for a week with it n the hospital.
Congrats! Good for you.
 
[Open Access] Shen M, Shi H. Sex Hormones and Their Receptors Regulate Liver Energy Homeostasis. International Journal of Endocrinology. http://www.hindawi.com/journals/ije/aip/294278/

The liver is one of the most essential organs involved in the regulation of energy homeostasis.

Hepatic steatosis, a major manifestation of metabolic syndrome, is associated with imbalance between lipid formation and breakdown, glucose production and catabolism, and cholesterol synthesis and secretion.

Epidemiological studies show sex difference in the prevalence in fatty liver disease and suggest that sex hormones may play vital roles in regulating hepatic steatosis.

In this review, we summarize current literature and discuss the role of estrogens and androgens and the mechanisms through which estrogen receptors and androgen receptors regulate lipid and glucose metabolism in the liver.

In females, estradiol regulates liver metabolism via estrogen receptors by decreasing lipogenesis, gluconeogenesis, and fatty acid uptake, while enhancing lipolysis, cholesterol secretion, and glucose catabolism.

In males, testosterone works via androgen receptors to increase insulin receptor expression and glycogen synthesis, decrease glucose uptake and lipogenesis, and promote cholesterol storage in the liver.

These recent integrated concepts suggest that sex hormone receptors could be potential promising targets for the prevention of hepatic steatosis.
 
Doctors,

I appreciate the studies but can you give us the bottom line?

Are any of the orals relatively safe for a four week period or are they all very toxic to the liver?

Thanks.
 
I use oral AAS for my firsts cycles, Winny and anavar, and I have used samarin to protect my liver. I guess it did work....I still have my liver :)


"Pain is temporary, Pride is forever»

If such conclusions were the justifiable norm in science, many alcoholics could legitimately argue the reason they did not develop cirrhosis is because they (unlike some of their binge drinking friends) drank continuously :)
 
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Doctors,

I appreciate the studies but can you give us the bottom line?

Are any of the orals relatively safe for a four week period or are they all very toxic to the liver?

Thanks.

I'll be happy to answer that question when YOU define "safe and toxic". I ask bc Tylenol is considered "safe" but it can also be quite "toxic".

Only YOU can decide if the risk of AAS use, no matter how small, is worth the benefit.
 
I had hepatitis when i was in my late 20's,i am now 68 and just had the hepatitis test done.I thought that once you got it you had it for life but my results show negative.I was in isolation for a week with it n the hospital.

I don't know if you ever found your answer but if not, then no. Hepatitis is not always a life long disease. There are a few different kinds of hepatitis (hep a, hep b, etc). I believe hep C is the only one that last for life but if untreated the others can shorten you life pretty quickly!
 
Hepatitis A once contracted runs it's course and is "cured" by the bodies immune system. Immunity is generally considered "lifelong".

Hepatitis C IS CURABLE, in select patients with optimal therapy, but it may also become a "chronic" condition in certain instances. Antibodies to Hep-C may persist for prolonged periods but especially in those who remain "infected".

Hepatitis B is somewhat different bc our ability to detect this virus is limited by it's ability to remain "dormant" within the hepatocytes for prolonged periods. Nevertheless essentially all of those who are or were infected with Hep-B show signs of that infection thru the use of serologic assays that check for the presence of specific antibodies to Hep-B or it's DNA.
 
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had hepatitus in late 20's in the hospital in isolation for a week.now 69 and this is my latest test results

hepatitus.jpg
 
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