Anadrol - the carcinogen

[Sigmund Froid]

It is generally suspected by the medical community that oxymetholone is carcinogenic. I will be the first to say that it is unfair to say that the evidence indicates that oxymetholone absolutely IS carcinogenic in humans. However, I think it is fair to say that the available evidence suggests that it is likely that oxymetholone is a carcinogen. Plus, with side effects like increased fat gain, injuries from too much strength too quickly, and now cancer, I think that methandienone (dbol) is a better bet. Anyway, here are a bunch of studies to support this idea. I will post the studies one at a time and attempt a criticism of each one. Here you go:

[Sigmund Froid]

TITL: Oxymetholone: I. Evaluation in a comprehensive battery of genetic toxicology and in vitro transformation assays. [comment on Toxicol Pathol. 1999 Sep-Oct;27(5):507-12] 10528629

AUTH: Holden H E; Studwell D; Majeska J B

ORGA: Department of Toxicology and Safety Assessment, Boehringer Ingelheim Pharmaceuticals, Ridgefield, Connecticut 06877, USA. [email protected]

PUB TYPE: Comment. Journal Article.

CITE: Toxicol Pathol 1999 Sep-Oct; 27 (5): 501-6

LANG: ENG; English

ABST: Oxymetholone is generally assumed to be a nongenotoxic carcinogen. This assumption is based primarily on the results of an Ames test, existing data in repeat-dose toxicology studies, and the predicted results of a 2-yr National Toxicology Program (NTP) rat carcinogenicity bioassay. To provide a comprehensive assessment of its genotoxicity in a standard battery of mutagenicity assays, oxymetholone was tested in microbial and mammalian cell gene mutation assays, in an in vitro cytogenetics assay (human lymphocytes), and in an in vivo micronucleus assay. Oxymetholone was also tested in an in vitro morphologic transformation model using Syrian hamster embryo (SHE) cells. These studies were initiated and completed prior to the disclosure of the results of the NTP bioassay. Oxymetholone was tested at doses up to 5,000 microg/plate in the bacterial plate incorporation assay using 4 Salmonella strains and the WP2 uvrA (pKM101) strain of Escherichia coil. There was no induction of revertants up to the highest dose levels, which were insoluble as well as toxic. In the L5178Y tk+/- mouse lymphoma assay, doses up to 30 microg/ml reduced relative survival to approximately 30% with no increase in mutants. Male or female human lymphocytes were exposed in vitro to oxymetholone for 24 hr without S9 or 3 hr with S9 and evaluated for the induction of chromosomal aberrations. There was no increase in aberration frequency over control levels and no difference between male and female cells. Peripheral blood from Tg.AC transgenic mice treated dermally for 20 wk with 0, 1.2, 6.0, or 12.0 mg/day of oxymetholone and from p53 transgenic mice treated orally by gavage for 26 wk with 125, 625, or 1,250 mg/kg/day of oxymetholone was evaluated for micronuclei in polychromatic and normochromatic erythrocytes. There was no difference in micronuclei frequency between control and treated animals. These results confirm that oxymetholone is not genotoxic in a comprehensive battery of mutagenicity assays. In the SHE assay, oxymetholone produced a significant increase in morphologically transformed colonies at dose levels of 13-18 microg/ml. The lack of genotoxicity of oxymetholone, the positive response in the in vitro transformation assay, and the results of transgenic mouse carcinogenicity assays will provide an interesting perspective on the results of an on-going NTP rat carcinogenicity bioassay.

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This was not performed on human subjects. However, what is carcinogenic for one mammal tends to be carcinogenic for other mammals. Also, the dosing protocol of bodybuilders isn't accurately reflected. Nevertheless, it suggests cancer causing properties that you probably wouldn't find with certain other steroids.

[Sigmund Froid]

TITL: Oxymetholone: II. Evaluation in the Tg-AC transgenic mouse model for detection of carcinogens. [comment on Toxicol Pathol. 1999 Sep-Oct;27(5):513-8] 10528630 [comment in Toxicol Pathol. 1999 Sep-Oct;27(5):501-6] 10528628 [comment in Toxicol Pathol. 1999 Sep-Oct;27(5):513-8] 10528630

AUTH: Holden H E; Stoll R E; Blanchard K T

ORGA: Department of Toxicology and Safety Assessment, Boehringer Ingelheim Pharmaceuticals, Ridgefield, Connecticut 06877, USA.

PUB TYPE: Comment. Journal Article.

CITE: Toxicol Pathol 1999 Sep-Oct; 27 (5): 507-12

LANG: ENG; English

ABST: Several rodent models are under examination as possible alternatives to the classical 2-yr carcinogenicity bioassay. The Tg.AC transgenic mouse has been proposed as a shorter term model offering the possibility of detecting nongenotoxic and genotoxic carcinogenic agents. Retrospective studies of chemicals with established carcinogenic potential have revealed a close correlation between classical bioassay results and the production of skin tumors in the Tg.AC mouse model. Oxymetholone is a synthetic testosterone derivative that is a suspected carcinogen but has shown no evidence of genotoxic activity in a comprehensive battery of genetic toxicity assays. It currently is being tested by the National Toxicology Program (NTP) in a 2-yr rat carcinogenicity bioassay. Because of its nongenotoxicity and the ongoing chronic bioassay, oxymetholone was considered an ideal candidate for a prospective evaluation of the predictive validity of the Tg.AC dermal carcinogenicity model. Consequently, a 6-mo dermal study with oxymetholone in the Tg.AC mouse model was initiated and completed prior to disclosure of the NTP rat bioassay results. In this study, male and female hemizygous Tg.AC mice, 7-8 wk old, were housed individually in suspended plastic cages. An area of dorsal skin was shaved to accommodate dermal applications of 200-microl doses of vehicle control (acetone), drug (1.2, 6.0, or 12 mg oxymetholone in dimethylsulfoxide:acetone, 20:80), or positive control (1.25 microg 12-o-tetradecanoyl-phorbol-13-acetate [TPA]) solutions. Mice received oxymetholone or acetone daily or TPA twice weekly for 20 wk followed by a 6-wk recovery period. The acetone control groups exhibited low spontaneous incidences of papillomas, whereas dermal application of oxymetholone produced dose-related increases in the numbers of papilloma-bearing mice and the numbers of papillomas per animal. Females showed a somewhat greater response to the androgen than did the males. TPA caused an unequivocal increase in papillomas, with males exhibiting a greater response than females. The results of this study indicate that this nongerotoxic androgenic compound possesses proliferative properties. The results predict that chronic systemic administration of oxymetholone will most likely be associated with increased incidences of neoplasms.
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This studies are nearly impenetrable because they are so immersed in scientific and biological terminology. I apologize if they aren't of much use to you. But here again, Anadrol was administered to mice and they developed cancer. Of course, bodybuilders don't take anadrol for 20 weeks straight. Another interesting thing was that they gave mice up to 20mg. That is huge and humans just don't take the equivalent for their bodyweight. Humans are hundreds of times heavier, and they take less than 10 times the dose. Of course, there was a group of mice that developed cancer from only 1mg...but again, for 20 weeks.

-SF

[Sigmund Froid]

TITL: Oxymetholone: III. Evaluation in the p53+/- transgenic mouse model. [comment on Toxicol Pathol. 1999 Sep-Oct;27(5):507-12] 10528629 [comment in Toxicol Pathol. 1999 Sep-Oct;27(5):507-12] 10528629

AUTH: Stoll R E; Holden H E; Barthel C H; Blanchard K T

ORGA: Department of Toxicology and Safety Assessment, Boehringer Ingelheim Pharmaceuticals, Ridgefield, Connecticut 06877, USA. [email protected]

PUB TYPE: Comment. Journal Article.

CITE: Toxicol Pathol 1999 Sep-Oct; 27 (5): 513-8

LANG: ENG; English

ABST: Oxymetholone has been identified as a suspected nongenotoxic carcinogen and has recently completed testing in a conventional National Toxicology Program (NTP) 2-yr rodent bioassay program. As a synthetic androgen with a limited historical database in toxicology, oxymetholone is an ideal candidate for prospective examination of the performance of short-term transgenic mouse models in the detection of carcinogenic activity. In the present series of 3 articles, studies are described where oxymetholone was evaluated prior to disclosure of the results of the NTP 2-yr bioassay. The accompanying articles provide evidence showing that oxymetholone is devoid of mutagenic activity yet elicits a positive carcinogenic response in the Tg.AC transgenic mouse model. In the present study, oxymetholone was administered by oral gavage to p53 heterozygous male and female mice for 26 wk at doses of 125, 625, and 1,250 mg/kg/day. The vehicle was 0.5% aqueous methylcellulose. Positive controls consisted of mice treated daily by oral gavage with 200 or 400 mg/kg/day of p-cresidine in corn oil. The oxymetholone-treated females showed significantly increased body weight gain and clitoral enlargement attributable to drug treatment. In addition, significant alterations in kidney, liver, and testis weights were attributable to oxymetholone. However, there were no neoplastic lesions that were attributable to oxymetholone in either sex. p-Cresidine produced unequivocal bladder neoplasms in both sexes at the high dose and in males at the lower dose. The absence of a neoplastic response with oxymetholone is consistent with the selectivity of the p53-/- mouse model for detecting carcinogens that act by genotoxic mechanisms.

[Sigmund Froid]

TITL: Enhancing effect of oxymetholone, an anabolic steroid, on development of liver cell foci in rats initiated with N-diethylnitrosamine.

AUTH: Shimoji N; Imaida K; Hasegawa R; Matsuoka C; Uneyama C T; Takahashi M; Hayashi Y

ORGA: Division of Pathology, National Institute of Hygienic Sciences, Tokyo, Japan.

PUB TYPE: Journal Article.

CITE: Cancer Lett 1990 Feb; 49 (2): 165-8

LANG: ENG; English

ABST: The promoting potential of oxymetholone (OXM) administration on development of liver cell foci was investigated in male F344 rats previously treated with N-diethylnitrosamine (DEN). One week after a single injection of DEN (100 mg/kg, i.p.), rats were given OXM at a dietary level of 0.2% for the first 4 weeks and then at a concentration of 0.1% for an additional 35 weeks. All rats were killed at week 40 for histopathological and immunohistopathological examination of liver tissue. The numbers and areas of both clear cell and glutathione S-transferase placental form (GST-P) positive foci were significantly increased in the group treated with DEN and OXM as compared with the respective values for the DEN alone group. The results thus suggested that OXM possesses promoting potential for rat liver carcinogenesis.

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Here again, the studies just don't seem to accurately mimic the normal use of androgenic anabolic steroids as self-administered by most steroid users. Do bodybuilders inject DEN? I don't think so. Do they take Anadrol for 39 weeks straight? I hope not.

[Sigmund Froid]

Here's some good news:

TITL: Long-term survival with tumor regression in androgen-induced liver tumors.

AUTH: McCaughan G W; Bilous M J; Gallagher N D

PUB TYPE: Journal Article.

CITE: Cancer 1985 Dec 1; 56 (11): 2622-6

LANG: ENG; English

ABST: Two patients with androgen-induced liver tumors, one of whom had been partially treated by a liver resection, are reported. Hepatocellular carcinoma was diagnosed on histologic grounds. The patients had been receiving androgen therapy for primary diagnoses of either hypopituitarism or paroxysmal nocturnal hemoglobinuria. After androgen withdrawal, both are alive and well with no evidence of residual tumor 10 and 14 years after diagnosis, respectively.

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I would like to get my hands on the full study, not just this abstract. I want to know how they know the liver cancer was "androgen-induced," though such a thing doesn't sound unlikely. The good news is that they were free from relapse 10 and 14 years later. I understand that for most cancers, if you survive 5 years without a relapse, you have excellent chances for survival...usually considered "cured," I believe.

-SF

[Sigmund Froid]

TITL: Occurrence of primary hepatocellular cancer and peliosis hepatis after treatment with androgenic steroids.

AUTH: Kew M C; Van Coller B; Prowse C M; Skikne B; Wolfsdorf J I; Isdale J; Krawitz S; Altman H; Levin S E; Bothwell T H

PUB TYPE: Journal Article.

CITE: S Afr Med J 1976 Jul 24; 50 (32): 1233-7

LANG: ENG; English

ABST: Three patients are reported in whom treatment of Fanconi's anaemia with androgenic steroids was complicated by the development of either primary hepatocellular cancer (PHC) or peliosis hepatis. The first, a White woman aged 34 years, was found to have PHC after receiving first methyltestosterone and then oxymetholone for a total period of 7 years. She died 4 months after the diagnosis was made. The other 2 patients were White children who presented with peliosis hepatis after receiving methyltestosterone and oxymetholone for 8 years and oxymetholone for 5 years, respectively. Both died from their primary diseases shortly after oxymetholone treatment was discontinued. Possible pathogenic mechanisms involved in the development of these serious complications are discussed and the therapeutic dilemma raised by their occurrence is emphasised.

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Again, bodybuilders don't take oxymetholone and methyltest for 8 years at a time.

-SF

[Sigmund Froid]

Here is my conclusion on this issue:

There exists no credible information that indicates that Anadrol, as dosed by most bodybuilders, has caused cancer.

However, Anadrol has been known to cause cancer under certain conditions.

Of course, there are plenty of things we couldn't prove caused cancer, and then they turned out to be carcinogens. This calls for personal evaluation and good judgment. If oxymetholone is generally suspected of being a carcinogen by the medical community, and they don't believe that dianabol is as carcinogenic in the same manner, then why not just play it safe and use dbol?

Here again, we see that we can't always rely on studies 100% - as Rickson pointed out. I apologize if the studies weren't very helpful to you. If nothing else, you can conclude that they are inconclusive - which is a sort of conclusion in itself. Also, I posted all the studies that I could find that had abstracts posted. There are a great many studies that exist that I couldn't find.

A search for "oxymetholone carcinogen" at any search engine will show you the general opinion of the medical community. Its on the list for "suspected and known carcinogens."

If there is something you can get out of Anadrol that you absolutely cannot achieve reasonably through the use of any other steroid, then it might be worth it to you depending on your situation. If you feel it would just take a few weeks longer using a different steroid that is not a suspected carcinogen, perhaps that would be a good idea too.

-SF