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Anabolic-Androgenic Steroids  

Perhaps one of the most effective ways of building body mass is to intake androgenic-anabolic steroids; although it’s positive effects are not limited to building muscle and are reported to assist in other areas of athletic performance such as endurance and speed.  However, because of adverse effects on the body, they are not allowed to be taken without a medical prescription.  Steroids are derivatives of cholesterol and are defined as “any of several fat-soluble organic compounds having as a basis 17 carbon atoms in four rings; many have important physiological effects”.  Androgenic effects are essentially the development of masculine characteristics in the human body while anabolic effects refer to synthesizing large tissue from simple compounds (in this case amino acids form proteins).  Anabolic steroids can be taken in several ways; they can be injected in to the muscle, they can be taken orally and they can be taken through gels/creams that are applied to the skin.

As discussed previously, steroid hormones are produced naturally within the body.  Anabolic steroids were originally developed to treat hypogonadism-when sufficient testosterone is not produced by the body.  What occurs at the molecular level when anabolic-androgen steroids are taken is the anabolic steroid diffuses across the cell membrane and combines with the hormone receptor which initiates the process of protein synthesis (refer to section II and Figure 7.1).

 

Figure 7.1-an anabolic steroid as it enters the cell and initiates protein synthesis

As mentioned previously, steroids are produced naturally within the body and are fat-soluble organic compounds with a tetracyclic framework derived from cholesterol.  The base structure of steroids is shown below:

 

There are three major classes of steroids, which are all produced in the adrenal cortex; glucocorticoids, mineralocorticoids, and androgens (although the androgens are mainly synthesized in the gonads-especially the testes and ovaries).  As androgens is the class which influences muscle growth the most, these types of steroids (such as testosterone-a key steroid which possesses both anabolic and androgenic properties) will primarily be focused on.

The complicated process in which cholesterol is converted to androgens (androstenedione and dehydroepiandrosterone) and then testosterone is illustrated in Figure 7.3.  Firstly, cholesterol is modified by the cytochrome P-450 enzyme, resulting in pregnenolone (figure 7.2).   Pregnenolone is essentially the originator of androgens.  Through the use of the 17b-hydroxysteroid dehydrogenase enzyme in the testes and ovaries, the androgens can be converted to testosterone.

 

Figure 7.2-line structures for cholesterol and pregnenolone, respectively

 

 

 

 

 

 

 

 

 

 

 

 

 

Figure 7.3-eventual conversion from cholesterol to testosterone

 

Figure 7.4-structure of testosterone

The most common prohormones (synthetically produced chemicals which are taken manually) are typically converted within the body into anabolic steroids such as testosterone, dihydrotestosterone (DHT), nandrolone (nortestosterone), and 1-testosterone, all of which will be discussed subsequently.  Some of the more familiar prohormones advertised for are 4-androstenedione, 4-androstenediol (4-AD), 19-norandrostenedione, 19-norandrostenediol, and 1-androstenediol (1-AD).  Because these are converted to steroids within the body and are not steroids as such themselves, they are legal in the U.S. without perscription until Janurary 19th, 2005 when laws banning prohormones will be implemented.

Within the body, testosterone can be converted to dihydrotestosterone (the most effective of male steroids) by the 5α-reductase enzyme.  What occurs is the double bond between C4 and C5 is downgraded to a single bond, thus allowing room for an additional hydrogen atom to bond to the two carbon atoms.  As shown in Figure 7.5, the new hydrogen atom on C5 is trans to the methyl group while the new hydrogen atom on the C4 can be either cis or trans due to the already present hydrogen atom.

 

 

 

 

Figure 7.5-structure of dihydrotestosterone

Nandrolone is very similar in structure to testosterone.  Following the reaction, a hydrogen atom has replaced the methyl group in C10.  Figure 7.6 shows the structure of nandrolone.

 

 

 

 Figure 7.6-structure of nandrolone

1-testosterone (1-dihydrotestosterone) is simply an isomer of testosterone, although it is claimed to be 700% more anabolic and 200% more androgenic than testosterone.  The structure of 1-testosterone is illustrated in figure 7.7.

Figure 7.7- structure of 1-testosterone

There are many negative consequences due to taking steroids, although many are reversible upon the termination of steroid intake.  Following is a list of possible adverse effects from steroids:

  • Disruption of hormonal production in the body
  • Reduction in sperm cell production and shrinkage of the testicles in men (testicular atrophy)
  • Baldness or loss of hair
  • Development of breasts in men (gynecomastia)
  • Enlargement of the clitoris and decrease of breast size in women
  • Coarsening of the skin in women
  • Increase in sex drive
  • Growth stunt in adolescences
  • Injury to tendons, ligaments and/or muscles
  • Cardiovascular diseases such as heart attack and stroke
  • Disruption of blood flow
  • Liver tumour and cysts can form on the liver, possibly rupturing and resulting in internal bleeding
  • Acne and cysts
  • HIV and hepatitis due to sharing and/or non-sterile needles
  • Psychological effects can include rage and delusions

The reason for gynecomastia in men is due to the conversion of testosterone (or another androgenic steroid) to an estrogen (the primary female sex hormone) through a reaction called aromatization (because ring ‘A’ becomes an aromatic ring), where the enzyme aromatase acts as a catalyst.  For example, testosterone can be converted in to an estrogen called estradiol, a type of estrogen.

 

 

 

   

Figure 7.8- structure of the estrogen, estradiol

Below is a table illustrating the characteristics of the prohormones mentioned earlier.  Note that conversion rate signifies the amount of the steroid that is converted to testosterone.

Table 7.1- characteristics of prohormones (as cited from Wikipedia, original author unknown. Retrieved from the Internet: http://en.wikipedia.org/wiki/Prohormone) 1

Prohormone

Converts to

Characteristics

4-androstenediol (4-AD)

testosterone

·  Research indicates a conversion rate of about 5.6%, which means that of the amount taken orally, 5.6% is converted to testosterone.

·  Relatively high rate of aromatization to estrogen, and consequently higher risk of side-effects such as gynecomastia brought on by excessive estrogen formation.

·  Exhibits significant androgenic properties, which may result in side effects such as male pattern baldness, acne, and enlarged prostate.

4-androstenediol (4-AD)

testosterone

·  Conversion rate of about 15.76%, almost triple that of androstenedione, due to utilization of a different enzymatic pathway.

·  No direct conversion to estrogen, though some secondary aromatization does occur through metabolism.

·  Appears to be less androgenic than its cousin, since it does not metabolize into the potent androgen dihydrotestosterone (DHT).

19-norandrostenedione

nortestosterone

·  Only slightly less anabolic than testosterone.

·  Low rate of aromatization to estrogen.

·  Low occurrence of androgenic side effects.

19-norandrostenediol

nortestosterone

Same as -dione, except (as with the andros ), the conversion rate is higher.

1-androstenediol (1-AD)

1-testosterone

(1-Dihydrotestosterone)

·     Very high conversion rate, owing to the fact that the liver serves primarily to "activate" the compound as it passes through rather than to break it down and excrete it, as is the case with other prohormones.

·     Cannot aromatize to estrogen either directly or through any of its metabolic products. However,1-Testosterone is highly andronergic being a Dihydrotestosterone derivative. Many side effects associated with excessive levels of DHT, including male pattern baldness, testicular shrinkage, benign prostate hypertrophy and acne can occur with 1-AD usage. (Journal of Organic chem. vol, 27 1962 iss.1)

 

 Because steroid abuse is a developing issue in the athletic community, testing for steroids have become mandated in events such as the Olympics.  To detect the presence of steroids within the body, a urine sample is collected from a human, which is then analyzed by a gas chromatograph and mass spectrometer (GC/MS).  A chromatograph is essentially device which is used in combination with a mass spectrometer and is used to separate mixtures before the sample is analyzed by the mass spectrometer.  A mass spectrometer is a device which allows the identification of a (unknown) compound based on its mass.

 

Figure 7.9 – a gas chromatograph.  The injector is heated resulting in the inputted chemical becoming a gas.  In the column, the mixture is then separated due to their volatility and the separated chemicals are carried through the tube by an inert gas.  Less volatile chemicals will travel with a greater speed than those with more volatility.  This diagram is copyrighted by the Oregon State University .  

 

  Figure 7.10 – a mass spectrometer.  Once the mixture has been separated and have entered the mass spectrometer, the chemicals are bombarded with electrons by the ionization source, causes the molecules to form radical cations and subsequently break into smaller pieces.  The cations are then accelerated and then pass through a magnetic plate and are deflected. The less the mass is, the more deflection occurs (see Figure 7.11).  This diagram is copyrighted by the Oregon State University .

 

 

 

 

 

   

 

Figure 7.11 – deflection of ions in a mass spectrometer 

 

 

 

 

 

 

 

 

 

 

 

Figure 7.12 -mass spectrum (a) and total ion chromatogram (b) of oxymetholone, an anabolic steroid.

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