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Page 6 of 6
All AAS Are Not Created Equal
In summary, though the class of drugs is primarily based upon the male sex hormone testosterone, AAS cannot be viewed as simply substituting or even increasing the natural production of testosterone. Testosterone, which is regulated through a negative feedback system (meaning if too much is produced, the manufacturing signal from the brain is reduced), pulses throughout the day several times, giving a peak-and-valley rhythm, with highs being two to three times the lows.27 Testosterone can be converted into metabolites with greater estrogenic or androgenic properties, depending upon the tissue the hormone reaches. Once the signal has been generated, the body deactivates and clears these hormones to ready the body for the next signal. These signals can be rapid, acting through non-genomic pathways, directly altering receptor sensitivity, enzymes or ion channeling; such actions occur in seconds to minutes and do not always require the androgen to enter the cell. Slower but more permanent responses are typically generated when testosterone (or a metabolite) combines with an androgen receptor, the pair then connecting co-regulators present in the cell before traveling to the cell nucleus (DNA center) where specific genes are activated or suppressed. Testosterone may also partially block the catabolic response to cortisol by competing with the glucocorticoid receptor or reducing a cell’s production of glucocorticoid receptors.
When minor alterations are made to testosterone (or related steroids), these changes affect how the body processes and responded to the drug. AAS can be taken orally if protected against the “first-pass clearance” of the liver and intestines, provide elevated concentrations for weeks to months when injected as a long-chain ester, or absorb across the skin or mucosal membrane of the mouth or nose. AAS are reliably anabolic, but the effects vary depending upon the drug used. Some carry significant androgenic potential, possibly leading to hair loss or urinary retention; others are more estrogenic and may stimulate the growth of breast tissue in men or promote water retention and fat gain. Skeletal muscle is stimulated rapidly but the majority of anabolic processes are based upon the activation of growth-promoting genes in the cell nucleus.
AAS must bind with the androgen receptor and combine with co-regulators to generate this anabolic stimulation. However, if the chemical changes made to the AAS alter the shape of the androgen receptor significantly, then the co-regulators may not be able to effectively combine with the AAS-AR complex and gene stimulation may be reduced or fail. Maximal skeletal muscle growth cannot be achieved unless the cell incorporates additional nuclei, which are provided by satellite cells. Satellite cells are prompted to combine with muscle cells under the influence of androgens and other cell factors produced by exercise. Satellite cells arise from pluripotent stem cells, which can become either fat cells or muscle cells. In an androgen-rich environment, pluripotent stem cells are influenced toward muscle development and away from fat development. This may account for some of the “cutting” effect seen with non-aromatizable AAS.
Clearly, there is much to digest in this article, but also a recognition of much still to be learned. Unquestionably, all AAS are not created equal and the tendency for regulators, researchers and the media to regard all AAS as the same is dangerous and misguided. As with any class of drug, simple molecular changes can result in drastically different responses and unanticipated benefits or risks. Science and athletes should each take heed of the lessons learned by the other to better direct future research. There are benefits and risks in using AAS. Until more specific information arises, the use of these agents should be monitored closely by health care professionals. Certainly, there are benefits to individuals and society in treating the relatively common androgen deficiency seen in adult males. Whereas testosterone replacement therapy will likely remain the cornerstone of such therapy, there is likely a place for the directed use of specific AAS, such as 19-nortestosterone. Recreational users and those involved in sports doping should approach the decision to use AAS with appropriate caution from a “health” point-of-view, recognizing also the social and legal consequences of illicit use.
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Research and Review 
