Toxicity Of Anabolic Steroids

  • Anabolic androgenic steroids abuse and liver toxicity.
  • Anabolic Steroids and Liver Toxicity | IronMag Bodybuilding Blog
  • Cardiotoxicity of Illicit Anabolic Steroid Use - American College of Cardiology
  • The cardiac toxicity of anabolic steroids - ScienceDirect
  • Cardiovascular Toxicity of Anabolic Steroids | Annual Review of Pharmacology and Toxicology

    Anabolic androgenic steroids abuse and liver toxicity.

    toxicity of anabolic steroids Anabolic steroids are synthetic derivatives of testosterone that were developed as adjunct therapy for a variety of medical conditions. Today they are most commonly steroivs to enhance athletic performance and muscular development. Both illicit and medically indicated anabolic steroid use have been temporally associated with many subsequent defects within each of the body systems. Testosterone is the preferred ligand of the human xnabolic receptor in the myocardium and directly modulates what testosterone, translation, and enzyme function. Consequent alterations of toxicity of anabolic steroids pathology and organ physiology are similar to those seen with heart failure and toxicity of anabolic steroids. Hypertension, ventricular remodeling, myocardial ischemia, and sudden cardiac death have each been temporally and causally associated with anabolic steroid use in humans.

    Anabolic Steroids and Liver Toxicity | IronMag Bodybuilding Blog

    toxicity of anabolic steroids

    Oct 27, Author: The steroid ring is composed of three 6-carbon rings and one 5-carbon ring joined, of which cholesterol is the most basic form and, indeed, the precursor. Although the term steroid includes all agents derived from this ringed structure, this discussion includes only testosterone and the anabolic-androgenic steroids AASs. Testosterone is the principle hormone in humans that produces male secondary sex characteristics androgenic and is an important hormone in maintaining adequate nitrogen balance, thus aiding in tissue healing and the maintenance of muscle mass anabolic.

    Testosterone has a dual action and can be described in terms of its androgenic and anabolic capacities. AASs are drugs derived from the modification of the testosterone molecule in order to augment or limit certain characteristics of testosterone. In general, testosterone has been altered to produce drugs that are more or less anabolic, are more or less androgenic , have differing affinity for the testosterone receptor, have different metabolic breakdown pathways, or are efficacious for oral use; they can also have any combination of these changes.

    Well over a thousand different compounds have been synthesized and studied since the s in the hope of producing compounds that have an anabolic or androgenic effect superior to that of testosterone.

    Biochemists quickly noted that additions or subtractions to the testosterone molecule at specific locations would have a somewhat predictable effect on the inherent qualities of said compound.

    In general, the goal of altering an AAS is to increase its anabolic characteristics and to decrease its androgenic features, thus multiplying the compound's desirable, anabolic, nitrogen-sparing effects and minimizing its generally undesirable, androgenic, virilizing effects.

    To date, however, complete dissociation of the anabolic effects of an AAS from its androgenic characteristics has not been possible. Clinical interest in the beneficial effects of these drugs has increased, and ongoing research will continue to uncover novel uses for these agents and will further define their mechanisms of action. Almost since their inception, testosterone and anabolic-androgenic analogues have been used and abused by individuals seeking to augment their anabolic and androgenic potential.

    By doing so, these persons aim to boost their physical performance in athletic endeavors or improve their physique. Stories of Eastern-bloc athletes receiving testosterone and AASs as part of their training regimens as early as the s abound.

    The Eastern-bloc weightlifters and track athletes subsequently ruled the athletic stage for decades. These drugs are now considered controlled substances in the United States schedule 2 and 3 , and many AASs have been withdrawn from the US market.

    In response, over-the-counter designer anabolic steroids have been created by modifying the chemical structure of AAS and adding them to dietary supplements. They are frequently marketed as a way to achieve classic anabolic steroid—like results from products sold legally. Severe side effects, including hepatotoxicity, cholestasis, renal failure, hypogonadism, gynecomastia, and infertility, have been attributed to the use of these OTC products.

    While some of these side effects may be reversible, more aggressive use may result in the same type of permanent end-organ damage seen in cases of long-term AAS abuse. Testosterone, the primary male sex hormone, is manufactured in the testes under the influence of luteinizing hormone LH in amounts of 2.

    Testosterone is produced under a negative feedback loop between the hypothalamus, the anterior pituitary, and the testes. Testosterone, dihydrotestosterone, and estrogen all act at the hypothalamus to exert negative feedback inhibition upon gonadotropin-releasing hormone GnRH.

    Since GnRH stimulates follicle-stimulating hormone FSH and LH release in the pituitary, this negative feedback can be seen to inhibit subsequent testosterone production and effect spermatogenesis. Testosterone activity is mediated via an androgen receptor that is present in various tissues throughout the human body.

    Testosterone binds to an intracellular receptor found in the cytosol of cells, forming a receptor complex that migrates into the nucleus, where it binds to specific deoxyribonucleic acid DNA segments. This, in turn, activates specific messenger ribonucleic acid mRNA to increase transcription, leading to an increased rate of protein synthesis; in the case of muscle cells, this means increased production of the proteins actin and myosin.

    After this process is complete, the receptor complex dissociates and is recycled along with the hormone, to repeat this process multiple times prior to metabolism. These anabolic actions of testosterone are thought to be primarily due to testosterone acting upon the androgen receptor in anabolic-responsive tissues. Androgenic effects are likely mediated via the same androgen receptor in androgen-responsive tissues under the influence of dihydrotestosterone DHT , which is produced by the interaction of 5-alpha reductase 5AR with testosterone and the subsequent reduction of the C double bond.

    Additionally, DHT cannot undergo further reduction, nor is it a substrate for aromatase; thus, it is not converted to estrogenic metabolites. DHT has been shown to bind avidly to receptors in tissues, such as skin, scalp, and prostate, and to exert times the androgenic effect of testosterone.

    Thus, the primary hormone mediating the androgenic effects of testosterone is actually the 5-alpha reduced DHT. At physiologic testosterone levels, nearly all androgen receptors are engaged. Therefore, supraphysiologic doses of testosterone or AASs would have no increased anabolic effect in healthy athletes unless other mechanisms of action existed. Because there are many agents in production and literally hundreds more that have been synthesized, this discussion focuses on the basics involving the steroid ring substitutions and how these substitutions affect the properties of the drug.

    Detailed analysis is limited to those agents that are available or have been approved for use in the United States. Anabolic-androgenic steroid AAS development was centered on the need for agents that exhibited different characteristics than did testosterone. In general, the goal was to develop agents that were more anabolic and less androgenic than testosterone, that were capable of being administered orally, and that had less effect upon the hypothalamic-pituitary-gonadal axis.

    Most AASs are derived from 3 compounds: The third compound is structurally identical to testosterone except for the deletion of the 19th carbon hence its name. These parent compounds offer different properties with regard to action and metabolism that are generally constant throughout the entire family of compounds. One of the first changes made to the testosterone molecule was the addition of a methyl group or an ethyl group to the carbon position.

    This addition was noted to inhibit the hepatic degradation of the molecule, greatly extending the molecule's half-life and making it active when administered orally. Prior to this, testosterone, dihydrotestosterone, and nortestosterone all required parenteral administration due to hepatic metabolism of ketosteroids; this metabolism occurred on the first pass, when the drugs were administered orally.

    However, adding a methyl group or an ethyl group did not produce a drug with the exact properties of the parent compound. The alteration of hepatic metabolism was noted to cause strain on the liver, and indeed all oral compounds with this C addition were found to cause dose-related hepatotoxicity.

    This small change was also found to lower these agents' interaction with aromatase. Testosterone esters have increasingly been used in replacement therapy, but abuse of these compounds has risen as well. A feature that all testosterone esters have in common is a testosterone molecule with a carboxylic acid group ester linkage attached to the beta hydroxyl group.

    These esters differ in structural shape and size; they function only to determine the rate at which the testosterone is released from tissue. Generally, the shorter the ester chain, the shorter the drug's half-life and quicker the drug enters the circulation.

    Once in the circulation, the ester is cleaved, leaving free testosterone. Methyltestosterone is a very basic anabolic-androgenic steroid AAS , with the only addition being a methyl group at C This eliminates first-pass degradation in the liver, making oral dosing possible. It also causes dose-related hepatotoxicity. Methyltestosterone is metabolized by aromatase to the potent estrogen alpha methyl estradiol and is also reduced by 5AR to alpha methyl dihydrotestosterone.

    This compound exhibits very strong androgenic and estrogenic side effects and is generally a poor choice for most, if not all, uses. Methandrostenolone has an added cis- 1 to cis- 2 double bond that reduces estrogenic and androgenic properties. However, it does undergo aromatization to the rather potent estrogen alpha methyl estradiol, but curiously, it does not show the in-vivo propensity for reduction by 5AR to alpha dihydromethandrostenolone to any large degree.

    This steroid was first commercially manufactured in by Ciba under the brand name Dianabol and quickly became the most used and abused steroid worldwide, remaining so to date. It jokingly came to be known as "the breakfast of champions" in sports circles. This agent is very anabolic, with a half-life of approximately 4 hours.

    The methyl group at C makes this AAS an oral preparation and potentially hepatotoxic. Ciba, as well as generic firms in the United States, discontinued methandrostenolone in the late s, but over 15 countries worldwide still produce it in generic form. Fluoxymesterone is a potent androgen that is produced under the brand name Halotestin. With the addition of a 9-fluoro group, it is a very potent androgen that has little anabolic activity. An added beta hydroxyl group inhibits its aromatization.

    Again, the C methyl group makes oral administration possible, but with hepatic concerns. Nandrolone decanoate is simply a nortestosterone molecule in which a carbon decanoate ester has been added to the beta hydroxyl group. This addition extends the half-life of the drug considerably. Nandrolone is a potent anabolic with a relatively favorable safety profile. Nandrolone is reduced by 5AR in target tissues to the less potent androgen dihydronandrolone.

    Its affinity for aromatization to estrogen is low, being perhaps times less than that of testosterone. Nandrolone and its several esters decanoate, phenylpropionate differ only in their half-lives, due to the difference in ester properties. Nandrolone is a relatively safe drug with minimal androgenic concerns and ample anabolic action at therapeutic doses. Nandrolone decanoate is an intramuscular IM preparation and lacks the hepatotoxic C group; however, this agent is one of the most widely abused AASs, due to its efficacy, safety profile, and worldwide manufacture.

    Ethylestrenol is an oral nortestosterone derivative and was marketed in the United States under the brand name Maxibolin, but it has since been discontinued. This agent differs from nandrolone by the addition of a alpha ethyl group to reduce first-pass metabolism, as well as by the deletion of the 3-keto group. This latter omission seems to reduce androgen receptor binding. Ethylestrenol is a mild AAS, having very little anabolic or androgenic effect at therapeutic doses.

    Trenbolone is a derivative of nandrolone with several additions. The addition of a cis- 9 to cis- 10 double bond inhibits aromatization, while a cis- 11 to cis- 12 double bond greatly enhances androgen receptor binding. This drug is androgenically and anabolically potent. It is comparably more androgenic than nandrolone due to its lack of conversion to a weaker androgen by 5AR, as is seen with nandrolone.

    Trenbolone is a European drug with a very high abuse record. In the United States, it is used in veterinary preparations as trenbolone acetate; as such, it has found its way into the hands of persons who wish to exploit its androgenic and anabolic potential. The second carbon substitution with oxygen is thought to increase the stability of the 3-keto group and greatly increase its anabolic component.

    This AAS is very anabolic, with little androgenic effect at a therapeutic dose. First marketed by Searle, DHT was discontinued in the mids.

    Due to its mild androgenic properties, oxandrolone is one of the few agents to be routinely abused by female athletes. Athletes, from weightlifters to boxers, use oxandrolone, seeking to increase strength without experiencing additional weight gain. Stanozolol is an active AAS, due to the stability afforded by the 3,2 pyrazole group on the A-ring, which greatly enhances androgen receptor binding. The C methyl group enhances oral availability. Stanozolol is highly active in androgen- and anabolic-sensitive tissue.

    It is a weaker androgen than DHT and exerts comparatively less androgenic effect. It will not aromatize to estrogenic metabolites. Athletes, many in track and field, have abused it.

    Cardiotoxicity of Illicit Anabolic Steroid Use - American College of Cardiology

    toxicity of anabolic steroids

    The cardiac toxicity of anabolic steroids - ScienceDirect

    toxicity of anabolic steroids

    Cardiovascular Toxicity of Anabolic Steroids | Annual Review of Pharmacology and Toxicology

    toxicity of anabolic steroids