dreed
09-22-2009, 05:48 PM
Testosterone esters: what they are and how they work
Much of the testosterone that is prescribed for the purposes of hormone therapy is in the form of testosterone "esters." An ester is simply a name for a chemical compound that is formed from reaction between a carboxylic acid and an alcohol. A simple chemical diagram of this reaction is shown below in Figure A. Figure B shows the chemical structure of free testosterone (chemical formula C19H28O2) as well as two different esters of testosterone (testosterone cypionate and testosterone enanthate).
There are a number of different esters of testosterone, including the commonly prescribed injectables of testosterone enanthate and testosterone cypionate, as well other esters such as acetate, propionate, phenylpropionate, isocaproate, caproate, decanoate, and undecanoate. Each of these different esters is a molecular chain composed of carbon, hydrogen and oxygen atoms. The main difference between the different esters is how many carbon and hydrogen atoms make up the chain. For example, the propionate ester is composed of 3 carbons, 6 hydrogens, and 2 oxygens, whereas the cypionate ester is composed of 8 carbons, 14 hydrogens, and 2 oxygens.
Esterification of testosterone is done in order to improve the solubility of testosterone in oil, which in turn slows the release of the testosterone from the site at which it enters the body.
Testosterone, in its free, non-esterified form, has poor solubility in either oil or water-- though it can be suspended in water. Non-esterified testosterone is available in an aqueous injectable form with the drug name "Aquaviron." However, this form of testosterone stays active in the body for only a very short period of time (only a matter of hours, which is explained further below). Because of this, it must be injected on a daily basis in order to maintain a continuous level of testosterone in the blood. Therefore it is rarely used for testosterone replacement therapy as an injectable.
Once you have added an ester group to testosterone, it becomes even less soluble in water and more soluble in oil. Additionally, as a general rule, the more carbon atoms there are in an ester, the more soluble the ester is in oil. For example, testosterone propionate (with 3 carbon atoms in the ester group) is less soluble in oil than testosterone cypionate (with 8 carbon atoms in the ester group). Remember, this is general, simplified rule for our purposes herein; the solubility of a molecule depends on structural factors that are beyond the scope of this section.
So, generally, the more carbons the ester group has, the more soluble in oil it becomes, and the less soluble in water. The term for this ratio between oil and water solubility is called the "partition coefficient"-- the higher the solubility in oil, the higher the partition coefficient.
The partition coefficient of the ester in question is important because is effects how long the drug itself stays in the system. If the testosterone transfers too quickly from the oil to the blood, the result is a sudden spike in testosterone which then rapidly drops once the dose has been used up. In the example of free testosterone injected into the muscle from a water suspension (as in Aquiviron, mentioned above), the testosterone is essentially immediately available to the bloodstream due to its low partition coefficient, and thus there is an immediate spike of testosterone which is used up quickly in the body.
Testosterone cypionate, on the other hand, has a high partition coefficient. When injected into the muscle, the drug remains in its esterified form in a deposit in the muscle tissue. From there, it will slowly enter the circulation as it is picked up in small quantities by the blood. Once the esterified testosterone is brought into the blood stream, "esterase enzymes" cleave off the ester chain in a process known as "hydrolization," thus leaving the testosterone in its free form to perform its various actions and effects.
When people speak of whether a particular testosterone ester is "fast acting" or "slow acting," they are usually referring to the partition coefficient/solubility in oil. As described above, esters with more carbon atoms will generally be more soluble in oil-- they are often referred to as "slow-acting" esters (they stay active in the system longer). Esters that are less soluble in oil are often referred to as "fast-acting" forms of testosterone, referring to the fact that they are more quickly available and used up in the blood stream.
For men who are using injectable testosterone, slow-acting esters tend to be preferred, as fewer injections are needed over time to keep the blood levels of T reasonably constant. Testosterone enanthate (7 carbons) and testosterone cypionate (8 carbons) both take about 8-10 days to be fully released in the system, and so they are typically injected once every 7-14 days. Testosterone propionate (3 carbons) takes about 3-4 days to be fully released in the system, and must be injected in smaller doses at least weekly if not twice weekly. For this reason it is not often used.
Much of the testosterone that is prescribed for the purposes of hormone therapy is in the form of testosterone "esters." An ester is simply a name for a chemical compound that is formed from reaction between a carboxylic acid and an alcohol. A simple chemical diagram of this reaction is shown below in Figure A. Figure B shows the chemical structure of free testosterone (chemical formula C19H28O2) as well as two different esters of testosterone (testosterone cypionate and testosterone enanthate).
There are a number of different esters of testosterone, including the commonly prescribed injectables of testosterone enanthate and testosterone cypionate, as well other esters such as acetate, propionate, phenylpropionate, isocaproate, caproate, decanoate, and undecanoate. Each of these different esters is a molecular chain composed of carbon, hydrogen and oxygen atoms. The main difference between the different esters is how many carbon and hydrogen atoms make up the chain. For example, the propionate ester is composed of 3 carbons, 6 hydrogens, and 2 oxygens, whereas the cypionate ester is composed of 8 carbons, 14 hydrogens, and 2 oxygens.
Esterification of testosterone is done in order to improve the solubility of testosterone in oil, which in turn slows the release of the testosterone from the site at which it enters the body.
Testosterone, in its free, non-esterified form, has poor solubility in either oil or water-- though it can be suspended in water. Non-esterified testosterone is available in an aqueous injectable form with the drug name "Aquaviron." However, this form of testosterone stays active in the body for only a very short period of time (only a matter of hours, which is explained further below). Because of this, it must be injected on a daily basis in order to maintain a continuous level of testosterone in the blood. Therefore it is rarely used for testosterone replacement therapy as an injectable.
Once you have added an ester group to testosterone, it becomes even less soluble in water and more soluble in oil. Additionally, as a general rule, the more carbon atoms there are in an ester, the more soluble the ester is in oil. For example, testosterone propionate (with 3 carbon atoms in the ester group) is less soluble in oil than testosterone cypionate (with 8 carbon atoms in the ester group). Remember, this is general, simplified rule for our purposes herein; the solubility of a molecule depends on structural factors that are beyond the scope of this section.
So, generally, the more carbons the ester group has, the more soluble in oil it becomes, and the less soluble in water. The term for this ratio between oil and water solubility is called the "partition coefficient"-- the higher the solubility in oil, the higher the partition coefficient.
The partition coefficient of the ester in question is important because is effects how long the drug itself stays in the system. If the testosterone transfers too quickly from the oil to the blood, the result is a sudden spike in testosterone which then rapidly drops once the dose has been used up. In the example of free testosterone injected into the muscle from a water suspension (as in Aquiviron, mentioned above), the testosterone is essentially immediately available to the bloodstream due to its low partition coefficient, and thus there is an immediate spike of testosterone which is used up quickly in the body.
Testosterone cypionate, on the other hand, has a high partition coefficient. When injected into the muscle, the drug remains in its esterified form in a deposit in the muscle tissue. From there, it will slowly enter the circulation as it is picked up in small quantities by the blood. Once the esterified testosterone is brought into the blood stream, "esterase enzymes" cleave off the ester chain in a process known as "hydrolization," thus leaving the testosterone in its free form to perform its various actions and effects.
When people speak of whether a particular testosterone ester is "fast acting" or "slow acting," they are usually referring to the partition coefficient/solubility in oil. As described above, esters with more carbon atoms will generally be more soluble in oil-- they are often referred to as "slow-acting" esters (they stay active in the system longer). Esters that are less soluble in oil are often referred to as "fast-acting" forms of testosterone, referring to the fact that they are more quickly available and used up in the blood stream.
For men who are using injectable testosterone, slow-acting esters tend to be preferred, as fewer injections are needed over time to keep the blood levels of T reasonably constant. Testosterone enanthate (7 carbons) and testosterone cypionate (8 carbons) both take about 8-10 days to be fully released in the system, and so they are typically injected once every 7-14 days. Testosterone propionate (3 carbons) takes about 3-4 days to be fully released in the system, and must be injected in smaller doses at least weekly if not twice weekly. For this reason it is not often used.