Free vs. Bound Testosterone

Free vs. Bound Testosterone

Only a small amount of testosterone is in free form, which can interact with the cellular receptors. Most of it will be bound to SHBG (sex hormone-binding globulin), albumin, and other proteins that temporarily prevent the hormone from having an effect. Steroid hormones bind much more strongly to SHBG than albumin (with approximately 1,000 times greater affinity), however, albumin is present at a level 1,000 times greater than SHBG. Thus, both proteins bind about equally in the body. In men the distribution of testosterone is usually around 45% bound to SHBG and approximately 53% bound to albumin; this means that the remaining 2% exists independently as free unbound hormone. Women have lower levels of free testosterone which are pegged at around 1%. Another protein called ABP (androgen binding protein) helps regulate androgen activity within the reproductive system but since it occurs only in these tissues, it has no bearing on muscle growth.

Also, it has to be remembered that the alteration of testosterone into new anabolic/androgenic steroids causes changes in the plasma protein binding affinity of these steroids.

Therefore, the percentage of free hormone is an important point because the higher it is, the more effective a compound should be on a milligram-for-milligram basis. Furthermore, this variance can be quite substantial between different compounds. For example; Proviron® (1-methyl dihydrotestosterone) bonds with SHBG many times more avidly than testosterone19 while mibolerone (7,17 dimethyl-nandrolone) and bolasterone (7,17 dimethyl- testosterone) show virtually no affinity for this protein at all (clearly the reason these steroids are such potent androgens).

Several factors influence SHBG levels in body fluids including gender and age. The most notable of these seem to be estrogen concentrations as well as thyroid hormone concentrations found in blood samples from patients.

There is usually a decrease in the amount of this plasma-binding protein as estrogen and thyroid levels fall, and an increase in SHBG as they rise. This protein has also been found to be greatly decreased due to raised androgen levels through the use of anabolic/androgenic steroids. These facts were supported by a German study done in 1989 that indicated a marked tendency towards reduction in SHBG levels with oral anabolic steroid stanozolol (Winstrol®). After only three days of daily .2mg/kg body weight dosage (~18 mg for a 200-pound man), SHBG has decreased almost by 50% among normal subjects. In contrast, though milligram-per-milligram outcomes are similar, the effect of stanozolol is much stronger than that of injectable testosterone enanthate.

This finding may have been reached depending on how it was administered. Although not involved in the German study, other studies comparing oral vs. transdermal estrogen can be consulted. With oral administration, there is a much bigger spike in SHBG levels probably because the liver produces SHBG.

Thus, these steroidal compounds may change the binding of free testosterone by reducing SHBG levels. Therefore, we should not assume that injectable Winstrol® (or injectable steroids in general) will have the same effect. It is also possible to increase the levels of free testosterone by competing with it for binding sites. When there are more steroid molecules to compete for available plasma protein binding sites, less testosterone will be bound up and thus will remain in an unbound state. Some other steroid hormones like dihydrotestosterone, Proviron®, and Oral-Turinabol(chlorodehydromethyltestosterone) exhibit a marked preference for this reaction. This indicates that if distinct anabolic/androgenic steroids cause changes in the level of free testosterone, then one can improve another's action through such ways.

For example, although Proviron® has poor anabolic activity as compared to other androgens it has a very high affinity for SHBG which makes it useful in removing some active steroids from tissues where they interact with SHBG molecules.

This discussion should not mislead us into thinking that binding proteins have no important function. They support the transport and operation of internal male hormones. Binding proteins also serve to shield the steroid from fast metabolism, ensuring a more constant blood hormone concentration as well as dispersing the hormone evenly throughout various body tissues. Moreover, the identification of SHBG-R (Sex Hormone Binding Globulin receptor) on the cell membrane surface for steroid-responsive cells indicates that there is more to this protein than just facilitating the movement of hormones. Yet changing how much hormone remains unattached can still affect drug power.