Liver Toxicity and Oral Steroids: Are the Risks Over-exaggerated?


by Mike Arnold

When it comes to the discussion of oral AAS, one topic I see come up more frequently than anything else is the fear of developing liver toxicity. This has led many BB’rs to administer these drugs for very brief periods of time, long before they have reached maximum effectiveness, or in some cases, to discontinue using them altogether. This is a fairly recent phenomenon, with today’s BB’rs advocating shorter and shorter cycles to the point that many have suggested limiting the use of oral steroids to a maximum of 4 weeks, lest the user suffer from serious liver damage, even when administering long-prescribed pharmaceutical preparations.

Certainly, this new idea is in bold contrast to the decades of steroid research which has been conducted in human beings at numerous universities. The point of this article is not meant to minimize the potentially serious side effects associated with irresponsible oral AAS use, but to inform the reader of the truth regarding this class of drugs and their risks to the liver.

Without wasting time, I will get right to the point and say that the toxicity of oral AAS and their overall risks to the liver, in general, have been greatly exaggerated over the last several years, leading many to adopt a position which is both unnecessary and ignorant. The truth is that liver toxicity is not one’s primary health concern when using oral steroids at reasonable dosages; cardiovascular health is, and while cardiovascular risk factors associated with orals AAS can be controlled, that is another topic for another day. To be blunt, in the average healthy person with no pre-existing liver conditions, it would take a small mountain of oral AAS consumed over a considerable period of time, in order to experience irreparable liver damage. The type, dose, and length of administration required to experience liver death is far beyond what the typical gym lifter (or even professional BB’rs) is willing to administer. Otherwise, we would see significantly more people requiring a liver transplant, but let me ask you a question. How many people do you know or how many pro BB’rs have you heard of that have required a liver transplant from oral steroid use?

You see, the liver is a very resilient organ, which is not only capable of sustaining a tremendous workload, but is actually able to repair itself in the event it does sustain damage. This is not surprising, given the fact that filtering toxins from the body is its primary job, necessitating a degree of “toughness” that other organs do not possess. In short, if we could liken the liver to a BB’r, it would be Mr. Olympia. In order for the liver to fail to the point of replacement, it must be provided with an extreme workload, to the point that its filtering capacity is consistently overwhelmed, leading to severe damage and an inability to regenerate. Remember, prescription anabolic steroids were originally developed for conditions which necessitated long-term use, treating maladies such as anemia & osteoporosis and recently they have been more frequently prescribed for those with wasting diseases. These conditions require treatment for longer than 4 weeks if they are to be effective. Therefore, physicians have regularly treated large numbers of patients for decades with doses similar to, and sometimes in excess of, common BB’ing dosages. If oral AAS (in general) presented a degree of risk so great that exceeding 4 weeks of use could lead to serious liver damage, these drugs never would’ve been considered as a viable treatment option in this population.

I am convinced that the reason for the recent change in mind-set regarding optimal cycle length with oral steroids has been largely due to the cycling recommendations of OTC designer steroid companies. Throughout the 70’s, 80’s, 90’ and early 2000’s, most oral cycles ran between 8-12 weeks in length, regardless of the compound employed. This mind-set didn’t begin to change until we saw the immergence of OTC designer steroids in the marketplace; particularly methylated compounds. There were two reasons why we witnessed OTC companies advising such short cycle guidelines, both of which are understandable. 1) Some of the designer steroids released onto the marketplace warranted short cycle lengths, such as M1T. However, many other methylated products could’ve been reasonably run significantly longer. 2) In order to avoid lawsuits by irresponsible users pushing things to the limit, these companies showcased wisdom in their recommendations. After all, some customers would interpret the legal status of these products to mean…”Use without discrimination”…and would administer larger dosages for longer periods of time. By keeping their cycle recommendations well within safety limits, they minimized the possibility of a potential lawsuit.

While there are no doubt some oral AAS which are best left for short-term use (4 weeks or less), the large majority can safely be used for between 8-12 weeks at standard dosages. Some of the oral AAS included in this group include: All traditional/script AAS (including Anadrol), the overwhelming amount of orals sold in the blackmarket, and numerous OTC designers. While I am not going to list appropriate cycle guidelines for each oral steroid in existence, this should provide the reader with an idea of just how many steroids can be responsibly used in the 8-12 week range.

For those of you who are more conservative or desire to take precautions against the hepatotoxic effects of oral AAS, there are several preventative measures, which can be taken to significantly reduce the strain placed on the liver. These include the implementation of various OTC supplements, as well as temporary abstinence from all other unnecessary liver toxic drug, such as alcohol, Tylenol, and various prescription medications. Most are relatively inexpensive and make a worthy addition to any oral steroid cycle, especially when AAS are used regularly.

In the next section of this article, I have re-printed some studies and abstracts from Pub-Med, which demonstrate a more accurate view of oral AAS and their potential to cause liver injury. See below.


Study #1: In the study below, the aim was to determine whether or not Anadrol positively affects insulin sensitivity (the answer appears to be yes).

Oxymetholone ameliorates insulin sensitivity in maintenance hemodialysis patients: a randomized controlled trial.

Author(s): Aramwit P, Kobpipat N, Satirapoj B, Kopple JD, Supasyndh O
Affiliation(s): Department of Pharmacy, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand. aramwit@gmail.com

Publication date & source: 2009-04, Clin Nephrol., 71(4):413-22.
Publication type: Randomized Controlled Trial; Research Support, Non-U.S. Gov't

AIMS:

To investigate the beneficial effects of oral oxymetholone on IR in hemodialysis (HD) patients by increasing skeletal muscle function and stimulating myocyte glucose uptake and metabolism. METHODS: In a randomized, controlled double-blind study, 44 patients were randomly assigned to one of two groups: a treatment group that received oxymetholone 50mg orally twice daily and a control group that received placebo twice daily for 24 weeks. IR was calculated by using HOMA, and dual-energy X-ray absorptiometry was used to determine body composition. All patients were encouraged to walk at least one kilometer daily and were monitored by the Barthel index activity score. RESULTS: 25 men (57%) and 19 women (43%) were studied. 23 subjects were in the control group, and 21 subjects were in the treatment group. The mean age of patients and the duration of dialysis were 43.5 +/- 9.9 years and 92.8 +/- 37.8 months, respectively. After treatment, the HOMA index and body fat mass (FM) were significantly decreased in the treatment group compared to those in the control group (10.8 +/- 16.4 vs. 3.1 +/- 4.5; p < 0.05 and 1.73 +/- 2.77 vs. 0.40 +/- 1.12 kg; p < 0.05, respectively). Concurrently, the mean change of fat free mass (FFM) in the treatment group was higher than that in the control group (3.24 +/- 1.74 vs. 0.65 +/- 1.21 kg, p < 0.05). Two patients in the treatment group experienced an elevation in serum liver enzymes (9.52%). CONCLUSION:

HD patients treated with short-term oral oxymetholone showed an increase in insulin sensitivity when compared to the placebo group, and this effect depended on changes in FFM and FM.

Note: When these test subjects were administered a full 100 mg daily dose of Anadrol for 24 weeks straight (6 months), only 2 out of the 21 subjects treated experienced notably elevated liver enzymes...and yet, some online posters believe Anadrol will “blow out” their liver if used for longer than 4 weeks at only 50 mg daily.


Study #2: Oxymetholone for the treatment of HIV-wasting: a double-blind, randomized, placebo-controlled phase III trial in eugonadal men and women.

Author(s): Hengge UR, Stocks K, Faulkner S, Wiehler H, Lorenz C, Jentzen W, Hengge D, Ringham G

Affiliation(s): Department of Dermatology, University of Dusseldorf, Dusseldorf, Germany. ulrich.hengge@uni-duesseldorf.de
Publication date & source: 2003-05, HIV Clin Trials., 4(3):150-63.

Publication type: Clinical Trial; Clinical Trial, Phase III; Randomized Controlled Trial

BACKGROUND:

Despite highly active antiretroviral therapy (HAART), chronic involuntary weight loss still remains a serious problem in the care of HIV patients due to various alterations in energy metabolism and endocrine regulation. Previous studies in HIV-positive men undergoing androgen replacement therapy or treatment with recombinant growth hormone (rGH) have shown partial restoration of lean body mass (LBM), but these treatments have largely not been sufficiently studied in eugonadal individuals.

METHOD:

A double-blind, randomized, placebo-controlled trial of 89 HIV-positive eugonadal women and men with wasting assigned to the anabolic steroid oxymetholone (bid or tid) or placebo for 16 weeks was performed. Body weight, bioimpedance measurements, quality of life parameters, and appetite were analyzed.

RESULTS:

Oxymetholone led to a significant weight gain of 3.0 +/- 0.5 and 3.5 +/- 0.7 kg in the tid and bid groups, respectively (p < .05 for each treatment versus placebo), while individuals in the placebo group gained an average of 1.0 +/- 0.7 kg. Body cell mass (BCM) increased in the oxymetholone bid group (3.8 +/- 0.4 kg; p <.0001) and in the oxymetholone tid group (2.1 +/- 0.6 kg; p <.005). Significant improvements were noted in appetite and food intake, increased wellbeing, and reduced weakness by self-examination. The most important adverse event was liver-associated toxicity. Overall, 43% of patients in the tid group, 25% of patients in the bid oxymetholone group, and 8% in the placebo group had a greater than 5 times baseline increase for ALT, AST, or gamma GT, while other adverse events were not increased over placebo. CONCLUSION:

Oxymetholone can be considered an effective anabolic steroid in eugonadal male and female patients with AIDS-associated wasting. The bid (100 mg/day) regimen appeared to be equally effective to the tid (150 mg/day) regimen in terms of weight gain, LBM, and BCM and was associated with less liver toxicity.

Note: Of the 89 people participating in this study, only 25% of the subjects receiving 100 mg of Anadrol daily experienced significantly elevated liver enzymes, while 43% of those receiving 150 mg daily did. Notice at the conclusion of the study that the author states that those receiving 150 mg of Anadrol daily did not gain any additional lean body mass compared to those receiving 100 mg per day, making the 100 mg/day dose equally effective, while resulting in reduced toxicity.


Study #3: Oxymetholone promotes weight gain in patients with advanced human immunodeficiency virus (HIV-1) infection.

Author(s): Hengge UR, Baumann M, Maleba R, Brockmeyer NH, Goos M

Affiliation(s): Department of Dermatology, University of Essen, Germany.

Publication date & source: 1996-01, Br J Nutr., 75(1):129-38.
Publication type: Clinical Trial; Randomized Controlled Trial

The effect of the testosterone derivative oxymetholone alone or in combination with the H1-receptor antagonist ketotifen, which has recently been shown to block tumour necrosis factor alpha (TNF alpha), on weight gain and performance status in human immunodeficiency virus (HIV) patients with chronic cachexia was evaluated in a 30-week prospective pilot study. Thirty patients were randomly assigned to either oxymetholone monotherapy (n 14) or oxymetholone plus ketotifen (n 16). Patients receiving treatment were compared with a group of thirty untreated matched controls, who met the same inclusion criteria. Body weight and the Karnofsky index, which assesses the ability to perform activities of daily life, and several quality-of-life variables were measured to evaluate response to therapy. The average weight gain at peak was 8.2 (SD 6.2) kg (+ 14.5% of body weight at study entry) in the oxymetholone group (P < 0.001), and 6.1 (SD 4.6) kg (+10.9%) in the combination group (P < 0.005), compared with an average weight loss of 1.8 (SD 0.7) kg in the untreated controls. The mean time to peak weight was 19.6 weeks in the monotherapy group and 20.8 weeks in the combination group. The Karnofsky index improved equally in both groups from 56% before to 67% after 20 weeks of treatment (P < 0.05). The quality of life variables (activities of daily life, and appetite/nutrition) improved in 68% (P < 0.05) and 91% (P < 0.01) of the treated patients respectively. Oxymetholone was safe and promoted weight gain in cachectic patients with advanced HIV-1 infection. The addition of ketotifen did not further support weight gain. These results suggest the need for a randomized, double-blind, placebo-controlled multicentre trial. Note: While this study does not directly address liver function markers, the researcher’s conclusion was that such therapy was considered “safe” and effective.


Abstract #1: Hepatic effects of 17 alpha-alkylated anaboli-androgenic steroids.

[No authors listed]

Abstract

AIMS:

Use of 17 alpha-alkylated anabolic-androgenic steroids (17alpha-AAS) has been connected to hepatotoxicity. These steroids are used clinically to treat anemia, to prevent weight loss, and to treat wasting syndrome. The most common types of 17alpha-AAS are Methyltestosterone, Oxandrolone, Oxymetholone and Stanozolol. Liver disease and the effects of some anti-HIV drugs may contribute to hepatic dysfunction. Signs of hepatic dysfunction are listed. For those experiencing jaundice and related malfunctions, discontinuing the drug enables patients to recover. In many cases those who did not exhibit jaundice may have developed a tolerance for the drugs. Side effects such as cholestatic jaundice only occurred in a small number of patients taking the recommended doses of 17alpha-AAS. Peliosis hepatitis, hepatic tumors, and hepatocellular adenomas are other reported side effects. Proper dosing and monitoring of anabolic steroids reduces the risk of hepatotoxicity.

Note: In a review of the literature above, the author clearly states that side effects such as jaundice have only occurred in a small amount of patients being treated with Anadrol. The author then goes on to state that those experiencing jaundice and other liver-related side effects recover upon discontinuance of the drug, with proper dosing and monitoring further reducing the risk of hepatotoxicity.

As you can see from the references above, even the most toxic prescription oral steroid, Anadrol, has been deemed safe for use when dosed responsibly and when combined with proper monitoring. The above studies ranged from 16-30 weeks in length using doses of 100-150 mg per day, yet only the minority experienced an elevation in liver enzymes which was concerning to the medical researchers. If Anadrol can safely be used for extended periods of time under appropriate circumstances, then it seem reasonable to ascertain that less toxic steroids, such as Dianabol, can still be used for traditionally accepted 8-12 week cycles.

 

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