Anavar (Oxandrolone)

Oxandrolone (Oxandrin) is an anabolic steroid created by Searle Laboratories, now Pfizer Inc. under the trademark Anavar, and introduced into the US in 1964.

As opposed to most other anabolic steroids Oxandrolone has two major advantages: First, it does not aromatize (convert to estrogen which causes gynecomastia - breast tissue). Second, it does not significantly influence the body's normal testosterone production (HPTA axis) at low dosages (10mgs). When dosages are high (this goes for any anabolic steroid) then your body feels that it has enough testosterone and it reduces the production of LH (luteinizing hormone) which no longer stimulates Leydig cells in testicles to produce testosterone therefore causing testicular atrophy (shrinking). Post Cycle Therapy (PCT) is of course needed for high dosages (40-50mg) of this synthetic derivative of testosterone because as the dosage increases the influence on HPTA is bigger. Lack of PCT will of course lead to protein catabolism until body's normal testosterone secretion is back to normal.

The drug was prescribed for a number of medical disorders causing involuntary weight loss, in order to promote muscle regrowth. It had also been shown to be partially successful in treating cases of osteoporosis. However, in part due to bad publicity from its abuses by bodybuilders, Oxandrolone was discontinued by Searle Laboratories in 1989. It was picked up by Bio-Technology General Corporation, now World Anabolic Supplements. who, following successful clinical trials in 1995, released it under the tradename Oxandrin.

It was approved for orphan drug status by the Food and Drug Administration (FDA) in treating alcoholic hepatitis, Turner's syndrome, and weight loss caused by HIV. In addition, the drug has shown positive results in treating anaemia and hereditary angioedema. In a randomized, double-blind study, patients with 40% total body surface area burns were selected to receive standard burn care plus Oxandrolone, or without Oxandrolone. Those treated with Oxandrolone showed improve body composition, preserved muscle mass and reduced hospital stay time.^[2] Other studies however have shown links between prolonged use of the drug and problems of liver toxicity similar to those found with other 17α-alkylated steroids. Even in small dosages, many users reported gastro-intestinalproblems such as bloating, nausea, skin rash and itching (hives), black, tarry stools or light-colored stools, depression, unusual bleeding, unusual swelling, yellowing of the eyes or skin, and diarrhoea.

In rare cases, serious and even fatal cases of liver problems have developed during treatment with oxandrolone. Oxandrolone may increase the amount of low density lipoprotein (LDL; 'bad cholesterol') and decrease the amount of high density lipoprotein (HDL; 'good cholesterol') in the blood. This may increase the risk of developing heart disease. Oxandrolone may damage the liver or increase LDL without causing symptoms. It is important to have regular laboratory tests to be sure that the liver is working properly and that LDL has not increased. Oxandrolone may also decrease fertility in men.

Before the Controlled Substances Act was passed to restrict the production, sale, and usage of anabolic steroids, Oxandrolone's characteristics lent itself well towards use by female athletes. Its specificity targeting the androgen receptor meant that, unlike many other steroids, it had not been reported to cause stunted growth in younger users (because it doesn't convert to estrogen, that's the reason women typically don't grow as tall as men — they have more estrogen) and at typical dosage rarely caused noticeable masculinising effects outside of stimulating muscle growth. It is not easily metabolised into DHT or estrogen. As such, a typical dose of 20-30 mg provided elevated androgen levels for up to eight hours. To increase effectiveness, bodybuilders typically "stacked" the drug with others such as Testosterone, further enhancing body mass gain.

Bodybuilders consider a normal dose for a novice 20–30 mg per day, when in fact 10 mg is more than enough for someone who has never used it^{[unreliable source?]}. Higher dosages not only lead to AR (Androgen Receptor) downregulation and HPTA suppression but also damage the liver being a 17α-alkylated steroid. It is specifically made 17α-alkylated because if it weren't the liver would consider it a toxin and destroy it.

Since Searle stopped production, biggest sellers are La Pharma Italy and British Dragon Thailand.

Testosterone

Testosterone is a steroid hormone from the androgen group. In mammals, testosterone is primarily secreted in the testes of males and the ovaries of females, although small amounts are also secreted by the adrenal glands. It is the principal male sex hormone and an anabolic steroid.

In men, testosterone plays a key role in health and well-being as well as in osteoporosis. On average, an adult human male body produces about forty to sixty times more testosterone than an adult female body, but females are, from a behavioral perspective (rather than from an anatomical or biological perspective), more sensitive to the hormone.^[1] However the overall ranges for male and female are very wide, such that the ranges actually overlap at the low end and high end respectively.

History

A testicular action was linked to circulating blood fractions—now understood to be a family of androgenic hormones—in the early work on castration and testicular transplantation in fowl by Arnold Adolph Berthold (1803–1861). Research on the action of testosterone received a brief boost in 1889, when the Harvard professor Charles-Édouard Brown-Séquard (1817–1894), then in Paris, self-injected subcutaneously a “rejuvenating elixir” consisting of an extract of dog and guinea pig testicle. He reported in The Lancet that his vigor and feeling of wellbeing were markedly restored but, predictably, the effects were transient (and likely based on placebo), and Brown-Séquard’s hopes for the compound were dashed. Suffering the ridicule of his colleagues, his work on the mechanisms and effects of androgens in human beings was abandoned by Brown-Séquard and succeeding generations of biochemists for nearly 40 years.

The trail remained cold until the University of Chicago’s Professor of Physiologic Chemistry, Fred C. Koch, established easy access to a large source of bovine testicles—the Chicago stockyards—and to students willing to endure the ceaseless toil of extracting their isolates. In 1927, Koch and his student, Lemuel McGee, derived 20 mg of a substance from a supply of 40 pounds of bovine testicles that, when administered to castrated roosters, pigs and rats, remasculinized them.^[2] The group of Ernst Laqueur at the University of Amsterdam purified testosterone from bovine testicles in a similar manner in 1934, but isolation of the hormone from animal tissues in amounts permitting serious study in humans was not feasible until three European pharmaceutical giants—Schering (Berlin, Germany), Organon (Oss, Netherlands) and Ciba (Basel, Switzerland)—began full-scale steroid research and development programs in the 1930’s.

The Organon group in the Netherlands were the first to isolate the hormone, identified in a May 1935 paper "On Crystalline Male Hormone from Testicles (Testosterone)" by Karoly Gyula David, E. Dingemanse, J. Freud and Ernst Laqueur. They named the hormone testosterone, from the stems of testicle andsterol, and the suffix of ketone. The structure was worked out by Schering’s Adolf Butenandt (1903–1995).

The chemical synthesis of testosterone was achieved in August that year, when Butenandt and G. Hanisch published a paper describing "A Method for Preparing Testosterone from Cholesterol." Only a week later, the Ciba group in Zurich, Leopold Ruzicka (1887–1976) and A. Wettstein, announced a patent application in a paper "On the Artificial Preparation of the Testicular Hormone Testosterone (Androsten-3-one-17-ol)." These independent partial syntheses of testosterone from a cholesterol base earned both Butenandt and Ruzicka the joint 1939 Nobel Prize in Chemistry.^[3] Testosterone was identified as 17β-hydroxyandrost-4-en-3-one (C₁₉H₂₈O₂), a solid polycyclic alcohol with a hydroxyl group at the 17th carbon atom. This also made it obvious that additional modifications on the synthesized testosterone could be made, i.e., esterification and alkylation.

The partial synthesis in the 1930s of abundant, potent testosterone esters permitted the characterization of the hormone’s effects, so that Kochakian and Murlin (1936) were able to show that testosterone raised nitrogen retention (a mechanism central to anabolism) in the dog, after which Charles Kenyon’s group^[4] was able to demonstrate both anabolic and androgenic effects of testosterone propionate in eunuchoidal men, boys, and women. The period of the early 1930s to the 1950s has been called "The Golden Age of Steroid Chemistry",^[5] and work during this period progressed quickly. Research in this golden age proved that this newly synthesized compound—testosterone—or rather family of compounds (for many derivatives were developed from 1940 to 1960), was a potent multiplier of muscle, strength, and wellbeing.^[6]

Deca-Durabolin (Nandrolone)

Nandrolone (19-nortestosterone) is an anabolic steroid that may be present naturally in the human body, albeit in minute quantities of less than 0.4 ng/ml.^{[citation needed]} Nandrolone is most commonly sold commercially as its decanoate ester (Deca-Durabolin) and less commonly as a phenylpropionate ester (Durabolin). Nandrolone decanoate is used in the treatment of osteoporosis in postmenopausal women (though now not recommended) at a dose of 50 mg every three weeks. It is also used for some aplastic anaemias.

Metabolism

The positive effects of the drug include muscle growth, appetite stimulation and increased red blood cell production and bone density. Clinical studies have shown it to be effective in treating anaemia, osteoporosis and some forms of neoplasia including breast cancer, and also acts as a progestin-basedcontraceptive. For these reasons,^{[citation needed]} in the United States nandrolone received FDA approval in 1983.

Because nandrolone is not broken down into DHT, the deleterious effects common to most anabolic steroids on the scalp, skin, and prostate are lessened to a degree; but is rather broken down to the much weaker androgen dihydronandrolone. The lack of alkylation on the 17α-carbon drastically reduces the drug's liver toxicity. Estrogenic effects resulting from reaction with aromatase are also mitigated as a result of the drug being a progestin, but effects such asgynaecomastia and reduced libido still occur in larger doses. Other side-effects can include erectile dysfunction and cardiovascular damage, as well as several ailments resulting from the drug's effect of lowering levels of luteinizing hormone through negative feedback. Erectile dysfunction is attributed to the weaker action of dihydronandrolone in the penis since dihydrotestosterone is a known sexual modulator.

Detection methods

Nandrolone use is indirectly detectable in urine tests by testing for the presence of 19-norandrosterone, a metabolite of this molecule. The International Olympic Committee has set a limit of 2.0 ng per ml of urine as the upper limit, beyond which an athlete is suspected of doping, and in the largest Nandrolone study performed on 621 athletes at the 1998 Nagano Olympic games no athlete tested over 0.4 ng per ml.

Heavy consumption of the essential amino acid lysine (as indicated in the treatment of cold sores) has allegedly shown false positives in some and was cited by American Shotputter C.J. Hunter as the reason for his positive test, though in 2004 he admitted to a federal grand jury that he had injected Nandrolone.^[1] A final possible cause of incorrect urine test results is the presence of metabolites from other anabolic steroids, though modern urinalysis can determine the exact steroid used by analyzing the ratio of the two remaining Nandrolone metabolites. As a result of the numerous overturned verdicts, the testing procedure was reviewed by UK Sport. On October 5 2007, five-time gold medalist for track and field Marion Jones was caught, when she admitted to taking it, and was sentenced to six months jail for lying to big sporting companies in 2000.^[2][3]

Publicized abuse cases

• Greg Rudsedski was tested positive for Nandrolone, however was cleared of all charges at a later date. This sparked a huge controversy.
• Roger Clemens was reported to have been injected with Nandrolone (Deca-Durabolin) by major league strength coach Brian McNamee during the 2000 baseball season.^[4]
• Barry Bonds is reported to have begun a regime of banned steroids and human growth hormones following his disappointment with insufficient acclaim for his past natural baseball achievements. In the 1999 spring training camp his trainer readily admitted to a Bonds' teammate that Bonds was doping the steroid Deca-Durabolin.^[5]
• UFC hall of famer Royce Gracie tested positive for Nandrolone after defeating his long time rival Kazushi Sakuraba, he was fined $2,500 and suspended for the remainder of his license.^[6]
• Former WWE and current TNA wrestler Kurt Angle failed a WWE drug test under the company's Wellness Policy after his prescription for Nandrolone had expired.
• Former MMA PRIDE fighter and olympic judoka Paweł Nastula, and former UFC champion Vitor Belfort tested positive for nandrolone in 2006.
• UFC fighter Sean "Muscle Shark" Sherk tested positive for Nandrolone Decanoate (Deca Durabolin) after successfully defending his Lightweight title against Hermes Franca on July 7, 2007. He was eventually stripped of the title and suspended for six months.
• Shawne Merriman violated the NFL Steroid Policy in October 2006, and his Attorney stated that he believed the substance he used was Nandrolone. Merriman claims it must have been in a tainted nutritional supplement he took regularly.
• Petr Korda became the first high-profile tennis player discovered ingesting a banned substance. Following a match at Wimbledon, Korda tested positive for nandrolone. Subsequently, he was banned from the sport for one year. Korda did not return to the professional tour; the ban effectively marked the end of his career.
• Shoaib Akhtar, a Pakistani cricketer, was given a two year ban in 2006 for testing positive for Nandrolone. Shoaib was sent back to Pakistan and missed the Champions Trophy. The verdict, however, was overturned by a three-man tribunal a month later.^[7]
• Edgar Davids, a Dutch football player, was suspended by FIFA in 2001 when he tested positive for the banned nandrolone.
• Basque footballer, Carlos Gurpegi was involved in a long running appeal, after he tested positive for 19- norandroterone. Both Carlos and his club, Athletic Bilbao claimed his innocence but he was eventually handed a two year ban until 31 July 2008.
• Mohammad Asif, a Pakistani cricketer, has twice tested positive for Nandrolone. He first tested positive in a dope test, that PCB conducted on its own behalf just before the Champions Trophy in 2006 and was sent back home from India and for the second time has been confirmed tested positive for a banned substance during Indian Premier League (IPL), on July 14, 2008.
• Linford Christie, a British Olympic athlete, tested positive for Nandrolone.^[8]
• Mike Cloud, a NFL player, tested positive for nandrolone in the late 2002 season. But he later sued MuscleTech claiming that one of their over the counter products caused the positive test.
• Famed stickball player Steve Tomasik has also been linked with the usage of nandrolone.