Testosterone, as the natural product drug and one of the most widely used AAS, is the most convenient choice for a reference drug to which all others will be compared.

Particular properties of testosterone that are of note include that it converts enzymatically both to DHT and to estradiol (estrogen). While with normal levels of testosterone these conversions are in fact desirable, with supraphysiological levels caused by drug adminstration they can be undesirable. DHT is at least three times more potent (effective per milligram) than testosterone at the androgen receptor (AR): therefore, in those tissues which convert testosterone to DHT, there is effectively three times as much androgen as elsewhere in the body. Thus, whatever level of androgen is experienced by the muscle tissue is multiplied threefold or more in the skin and in the prostate. This can be excessive. Proscar could be used to keep DHT levels more or less normalized despite heavy testosterone use, however.

Excess conversion to estrogen is also undesirable since it contributes to inhibition of the hypothalamic/pituitary/testicular axis (HPTA), can cause or aggravate gynecomastia, can cause bloating, and can give unfavorable fat pattern distribution. This conversion can be somewhat reduced by use of aromatase inhibitors such as Cytadren, and/or the effects of the estradiol produced may be blocked in many tissues, including the hypothalamus and breast tissue, by Clomid.

Among the most significant differences of synthetic AAS compared to testosterone is that they may avoid either or both of these enzymatic conversions. Another difference results from the fact that not all activity caused by androgens is mediated by the androgen receptor, and not all AAS are comparably effective in these other activities.

Testosterone used alone is capable of giving very effective results, particularly with doses over one gram per week, and can give substantial results with only 500 mg/week. If no other drugs are used, however, side effects such as gynecomastia are fairly likely. Prostate enlargement, worsening of acne, and acceleration of male pattern baldness (for those genetically susceptible to it) are particularly severe because of the effectively-higher androgen levels seen in these tissues as a result of local conversion to the more-potent DHT. Synthetics which do not convert to DHT give only the same effective level of androgen in these tissues as in the body as a whole, rather than effectively three times the level. This is a significant advantage.

A particularly interesting property of testosterone is its low toxicity, exclusive of the above-mentioned side effects. Doses of two grams or four grams per week are hardly unknown in bodybuilding, and are not particularly hard on the liver. No one seems to want to take doses of any other single steroid at comparably-effective doses, and it seems that if one tried, they might be more toxic. E.g., the hepatotoxicity of Winstrol Depot resulting from its 17a -methyl group is not severe at doses of say 350 mg/week, but might well be problematic at a dose of two grams per week – though that is speculation, since no one I have heard of uses such doses of Winstrol. Thus, at the higher dosage regimes testosterone appears to have an advantage in terms of toxicity vs. effectiveness over many of the synthetics. These doses, however, are in the pro bodybuilder range. In the dosage range more appropriate for most individuals, the reverse is often the case.