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Chemical Name |
17a-methyl-17b-hydroxy-1,4-androstadien-3-one |
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Synonyms |
Dianabol (D-bol), Methandienone, Nerobol |
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Half Life |
3 – 6 hours |
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Anabolic: Androgenic ratio |
1:1–1:8 (1:1 Testosterone as standard in rodents) |
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Structural modifications
The addition of a methyl group at the 17α position of the D-cyclopentane ring slows first-pass metabolism in the liver, allowing it to circulate longer than testosterone.
The double bond between C1 and C2 of the A-cyclohexane ring has a weaker relative binding affinity for the androgen receptor (AR) than testosterone, reducing the androgenicity of the compound.
The History of Dianabol
Methandrostenolone was first reported in the literature in 1955 and was introduced to the US prescription market in 1958 by Ciba Pharmaceuticals under the drug name Dianabol.
A derivative of testosterone, the compound was modified to reduce androgenicity and preserve anabolic activity.
Historically, Dianabol is the most commonly used C-17a alkylated oral steroid for physique enhancement purposes, but its history is also deeply rooted in medical prescription.
Developed by Dr. John Ziegler, the team physician for the U.S. Olympic team, to reduce competition from Russia, which was already using testosterone in its athletes, methandrostenolone, a compound that was less androgenic but retained anabolic properties, brought a new dynamic to competitive sports and soon led to advancements in the sport.
However, less than five years later, a new wave of steroid abuse began to emerge in the sporting world as many athletes ignored the initial prescription guidelines of 5-15 mg and took the compound.
In 1970, the FDA required Ciba to clarify and publish the approved uses of methandrostenolone, accepting the position that it was "probably effective" in the treatment of osteoporosis and pituitary deficiency dwarfism, while continuing to study its effects on wasting diseases.
There are several reports in the literature of its use in pediatric dystrophies.
In 1983, Ciba withdrew Dianabol from the U.S. market and in 1985, the FDA removed methandrostenolone generics from the market entirely.
The Anabolic Steroid Control Act of 1990 banned its non-medical use in the United States.
Metabolism and Excretion of Methandrostenolone
Methandrostenolone is metabolized primarily in the liver by the following reactions: 6β-hydroxylation, 3α and 3β-oxidation, 5β-reduction, 17-epimerization, and conjugation, and is excreted in the urine.
Human mitochondrial steroid hydroxylases CYP11B1 and CYP11B2 (non-liver derived) have also been shown to be able to metabolize the compound, forming 11β-hydroxy and 18-hydroxy metabolites.
Unconjugated, beta-glucuronidated, and sulfated metabolites were also observed in urine.
Prolonged use of methandrostenolone at high doses may result in the appearance of unmetabolized drug in the urine.
Side Effects of Dianabol (Methandrostenolone)
Androgenic
Although methandrostenolone is technically an anabolic steroid, it can cause androgenic side effects such as oily skin, acne, and body/facial hair growth due to its sebaceous gland androgenic effects.
Women should be aware of potential masculinizing effects such as deepening of the voice, menstrual cycle irregularities, facial hair growth, and clitoral enlargement.
Clinical records of 2 prepubertal girls treated with Dianabol cream by their primary care physician for 6 and 8 months for anal eczema were reported.
Both girls had accelerated growth rate and bone maturation, clitoral enlargement, and deepening of the voice.
In one girl, all symptoms except the deep voice disappeared 6 years after treatment was discontinued.
Although it is possible for methandrostenolone to be converted to 5-alpha-dihydromethandrostenolone via 5-alpha reductase, the rate of conversion is very slow due to its low binding affinity for 5-alpha reductase.
Thyroid.
Thyroid-binding hormone globulin (THBG) levels have been shown to be affected by doses as low as 10 mg, potentially resulting in higher levels of free circulating thyroxine and triiodothyronine.
Estrogen.
Due to this structural modification, methandrostenolone is similar to boldenone (except for the 17α methyl group) and has the same degree of aromatization as boldenone.
However, methandrostenolone is much more estrogenic than estradiol because it is converted to 17α-methylestradiol, a potent estrogenic metabolite that is resistant to metabolism and has higher biological activity than estradiol.
Testosterone Suppression (HPTA)
Elevated estrogen or elevated serum testosterone levels cause negative feedback on the hypothalamic-pituitary-testicular axis (HPTA), resulting in HPTA suppression observed at moderate doses.
A 15 mg dose of methandrostenolone has been shown to decrease plasma testosterone levels by 69%.
In the absence of secondary or primary hypogonadism, a return to normal HPTA function is common after 6-8 weeks of discontinuation.
Another important clinical observation is that a decrease in sex hormone-binding globulin (SHBG) has been observed with methandrostenolone use, resulting in higher circulating free testosterone levels.
"In women, methandrostenolone has been shown to cause menstrual problems, resulting in irregular menstrual cycles."
Methandrostenolone is a sperm suppressant.
In subjects taking 15 mg for two months, sperm density per milliliter decreased by 46% and 73%.
Three of the subjects developed azoospermia, and one of them had a sperm count of only 1 million sperm per milliliter after two months of drug use.
The percentage of motile cells decreased by about 30% in two months.
The percentage of sperm with normal configuration decreased significantly, from 73±8% to 65±5% and 42±23% at both one and two months, respectively.
The percentage of sperm with amorphous heads increased by about 100% during 2 months of use; however, the changes in sperm morphology and production were observed to be reversible.
Hepatotoxicity (liver)
Being a C17-α alkylated compound, it protects the molecule from passing through first-pass hepatic metabolism, allowing a very high percentage of the compound to enter the bloodstream after oral administration.
The literature clearly shows an association between methandrostenolone and hepatic jaundice, hepatitis, cholestasis, and liver parenchymal cell changes. In rare cases, cholestatic jaundice can lead to kidney failure and potentially death.
In rare cases, liver dysfunction combined with environmental factors can lead to liver cancer.
Elevations of bilirubin, alkaline phosphatase (ALP), alanine transferase (ALT), and aspartate transferase (AST) should be closely monitored during and after use with blood tests by a physician.
Case report of a 28-year-old bodybuilder hospitalized for jaundice.The patient had been taking methandrostenolone 10-50 mg orally and stanozolol 50 mg intramuscularly every other day for 80 days for 3 weeks prior to hospitalization.
The bilirubin concentration was elevated to 4.5mg/dl, bile secretases were normal, and transaminase activity was elevated.
Liver biopsy was compatible with cholestasis induced by anabolic steroids.
The steroids were discontinued, but the patient's general condition worsened over 7 weeks.
Serum bilirubin rose up to 77.9 mg/dl.
He also developed renal failure with a creatinine concentration of 4.2 mg/dl.
Simultaneously with the administration of ursodeoxycholic acid (UDCA), a bile acid derivative, the patient's condition improved, and after a few weeks the biochemical values gradually reached normal levels.
In this case, there was a remarkable temporal coincidence between the administration of ursodeoxycholic acid and a significant clinical improvement.
Thus, TUDCA may be a viable compound as a preventive treatment.
Cardiovascular (cholesterol/lipids)
There are reports that methandrostenolone may cause an increase in serum total cholesterol due to an increase in LDL (bad) cholesterol and a decrease in HDL (good) cholesterol.
The decrease in serum HDL is mediated by hepatic triglyceride lipase, an enzyme that regulates serum lipids.
Oral C17-α alkylated AASs stimulate hepatic triglyceride lipase, resulting in a decrease in serum HDL.
When administered as an injectable, they have a lesser effect on this enzyme because they enter the circulation bypassing the liver.
Kidneys (kidneys)
Methandrostenolone is not directly nephrotoxic, but may increase renal arterial blood pressure, possibly by potentiating the renin-angiotensin-aldosterone system (RAAS) with upregulation of endothelin.
The RAAS may increase blood pressure and water retention by promoting tubular sodium and water reabsorption.
Acute kidney injury (AKI), which correlates with an increase in serum creatinine, can also occur.
Neurochemical (neurotoxicity)
Although attempts have been made in the past literature to link violent crime and anabolic steroid use, the results are inconclusive in light of other polydrug abuse.
No effect of methandrostenolone on brain reward performance was observed, but a small effect was observed with testosterone, which may affect the sensitivity of the brain reward system.
No effects were observed on changes in hippocampal activity in rats treated with methandrostenolone.
Reported clinical use
The earliest reports of clinical use were in pediatrics to treat pediatric muscular dystrophy and to address growth problems in prepubescent male patients.
Subsequent clinical use of methandrostenolone has focused on increased nitrogen retention and subsequent decreased nitrogen excretion (30% reduction), and increased serum protein levels to aid in tissue repair and shorten healing time after surgery, burns, fractures, or skin grafts.
There are also reports of its use in geriatric conditions, debilitating conditions, after chronic infections (tuberculosis), to help retain calcium in patients with osteoporosis, and to increase red blood cell counts in anemic patients.
The interaction of steroid hormones is not limited to androgen receptors, and there have been several reports that methandrostenolone interacts with glucocorticoid receptors, blocking their activation and resulting anti-inflammatory effects.
Methandrostenolone has also been shown to reduce circulating cortisol levels by inhibiting corticotropin production or release, thereby reducing the rate of production of adrenocortical steroids.
There are also studies suggesting that methandrostenolone may increase insulin resistance in diabetic patients, potentially through an increase in visceral adipose tissue (VAT), but as with previous AAS users, further research is needed.
Athletes and strength training
The first report of methandrostenolone being used for physical enhancement was a 2.48 kg (5.45 lb) increase in lean muscle tissue after taking 5 mg for three weeks, and it has been shown to help maintain and restore strength after 12 weeks of no training.
Anti-Doping / Anti-Fake Supplements
Since the mid-2000s, dietary supplements have been scrutinized for their potential to contain AAS, especially prohormones, which were readily available at the time.
In a study of 103 supplements, three were found to illegally contain undisclosed amounts of methandrostenolone.
From an anti-doping perspective, it's good for consumers to be aware of what's in the products they buy, which is why there's been a particular focus on detecting AAS in dietary supplements in recent years, with new detection methods constantly being developed and improved.
Reported deaths
The majority of deaths associated with methandrostenolone use reported in the literature are related to myocardial infarction or progression of cardiovascular disease.
However, most cases are reported as reactions to polypharmacy rather than to a specific substance.
Dietary Supplements to Consider When Using Methandrostenolone
Because methandrostenolone is a hepatotoxic C17-α alkylated compound, special attention should be paid to preventive management of hepatic cholestatic impairment and management of bile metabolism.
Consideration should be given to the use of bile acids such as tauroursodeoxycholic acid (TUDCA) and synthetic bile derivatives such as Ox-Bile to support bile flow, and fat-soluble compounds such as choline and inositol to support fat metabolism in the liver.
As well as lipotropic compounds such as choline and inositol to aid fat metabolism in the liver. Supplement Needs Dr Dean St Mart - Liver Stack
(https://www.supplementneeds.co.uk) is a combination of 1000mg ox bile, 800mg TUDCA, 800mg choline, and 800mg inositol.
Care should be taken to avoid co-administering methandrostenolone with TUDCA as this may increase hepatocellular uptake of methandrostenolone and thus increase hepatotoxicity
Dianabol Dosage (Dosage)
Doses of 0.1-0.3 mg/kg were originally prescribed to children for the treatment of muscular dystrophy.
For men, the initial prescribing guidelines were to take 5 mg daily and not take it for more than 6 weeks in a row.
While this was an effective dose in the early days, today, doses of 30-50 mg are observed to produce very noticeable and rapid results when it comes to physique enhancement and athletic performance.
One paper on athletic performance published in 1981 reported that a dose of 100 mg was well tolerated for six weeks, although health metrics were not closely monitored.
Several other reports in the early literature showed doses as low as 0.6 mg/kg.
For women, a dose of 2.5 mg was originally prescribed for osteoporosis.
However, women should be mindful of the potential feminizing side effects as discussed earlier.
Availability of Dianabol
Although Dbol (methandrostenolone) is a controlled substance in South Korea, it is still popular among bodybuilders where it is sourced through underlab.
However, methandrostenolone is readily available without a prescription in certain countries, and in Asia and many Eastern European countries, it is manufactured in under-the-counter facilities such as Alpha Pharma (India) and Balkan Pharma (Moldova).
