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A very small amount of testosterone is actually in the free form stage, in which interaction with cellular receptors is possible. The majority will be bound to the proteins SHBG (sex hormone binding globulin, also referred to as sex steroid binding globulin and testosterone-estradiol binding globulin) and albumin, which temporarily prevent the hormone from exerting activity. The distribution of testosterone in men is typically 45% of testosterone bound to SHBG, and about 53% bound to albumin. The remaining 2% of the average blood concentration exists in a free, unbound state.

The level of free testosterone available in the blood is likewise an important factor mediating its activity, as only a small percent is really active at any given time. It must also be noted that as we alter testosterone to form new anabolic/androgenic steroids, we also typically alter the affinity in which our steroid will bind to plasma proteins. As the higher percentage we have of free hormone, the more active the compound should be on a milligram for milligram basis.

The level of SHBG present in the body is also variable, and can be altered by a number of factors. The most prominent seems to be the concentration of estrogen and thyroid hormones present in the blood. Generally there is a reduction in the amount of this plasma binding protein as estrogen and thyroid content decreases, and a rise in SHBG as they increase. A heightened androgen level due to the administration of anabolic/androgenic steroids has also been shown to lower levels of this protein considerably.

Lowering the level of plasma binding proteins is also not the only mechanism that allows for an increased level of free testosterone. Steroids that display a high affinity for these proteins may also increase the level of free testosterone by competing with it for binding. Obviously if testosterone finds it more difficult to locate available plasma proteins in the presence of the additional compound, more will be left in an unbound state.

So clearly if the level of free-testosterone can be altered by the use of different anabolic/androgenic steroids, there also exists the possibility that one steroid can increase the potency of another through these same mechanisms. Binding proteins act to protect the steroid against rapid metabolism, ensure a more stable blood hormone concentration and facilitate an even distribution of hormone to various body organs. It remains although very clear however, that manipulating the tendency of a hormone to exist in an unbound state is an effective way to alter drug potency.

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