Testosterone Types and Delivery
Overview
In testosterone therapy , testosterone (often called "T" for short) can be administered into the body in a number of ways. The most common method is intramuscular (IM) injection with a syringe. Other delivery methods include transdermal application through gel, cream, or patch applied to the skin; orally by swallowing tablets (this method is uncommon as it has been shown to have negative effects on the liver); sublingually/buccally by dissolving a tablet under the tongue or against the gums; or by a pellet inserted under the skin. The T-delivery method used will depend on the type of medication available in the country of treatment, the health risks/benefits for the patient of the delivery method in question, personal preference, and cost.
Testosterone is not stored by the body for future use, so in order to maintain healthy levels, it must be administered in timed intervals, and in appropriate dosages. Injectable and subcutaneous T pellets remain active in the body the longest. Injectable T is typically administered between once a week to once every three weeks, and subcutaneous T pellets are replaced every 3-4 months. Transdermal T (patch, gel, or cream) is typically applied to the skin in smaller daily doses; oral and sublingual/buccal T are also typically taken daily.
"Normal" testosterone Levels
An individual's testosterone levels are usually confirmed through a blood test called a "serum total testosterone test ." Testosterone exists in your bloodstream in two forms-- "bound" testosterone and "free" testosterone . The majority of bound testosterone in the body is chemically bound to a protein called "sex hormone binding globulin" (SHBG). The remaining bound testosterone in the system is mostly bound to albumin, another protein . Free testosterone is considered the "active" form of testosterone , as it is not chemically attached to any proteins; thus, it is readily available to bind to androgen receptor sites on cells.
A serum total testosterone test measures the total of these two forms of T. What are considered normal test levels of combined bound and free testosterone in male bodies can range anywhere from 300-1100 ng/dl (nanograms per deciliter). Levels will vary with age and individual factors.
It is useful to also measure the level of free testosterone in the system, as this may be more indicative of how hormone therapy is progressing. Levels of free testosterone can range between 0.3%-5% of the total testosterone count, with about 2% considered an optimal level. Ask your doctor to check for both total and free levels of testosterone in your system.
A note of caution about greatly increasing your T dosage
During the first months of T therapy, many men feel impatient waiting for changes to happen. Some may consider doubling or tripling their dose, thinking that the more they put in, the faster the changes will come. However, dramatically increasing your dose might have the effect of slowing your changes. This is because excess testosterone in your body can be converted into estrogen by an enzyme called "aromatase." This conversion is part of the body's natural feedback system-- if there is an abundance of testosterone in the body, it is converted ("aromatized") to estrogen in order to maintain a "normal" hormonal balance. Therefore, taking very large doses of testosterone might not be a great idea. Be patient; if you are not seeing results in a reasonable period of time, and/or your T levels are low, discuss modifying your dosage with your doctor.
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 repla***ent 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 prescribed for men in transition.
Testosterone delivery methods
Injectable testosterone
The dosage amount and timing for injectable testosterone will depend largely upon which ester is being used, as well as the individual's own response to the hormone . In general, dosages will vary between 50 mg and 300 mg per injection , depending on the ester and the dosing regimen. An average injectable dose is about 200-250 mg every two weeks, though many trans men inject 100 mg every week or every 10 days, or other variations depending on their own bodies' needs and sensitivities. Again, the exact dosage required will vary from person to person, and health and well-being should be carefully monitored while determining an individual's ideal dose.
Some doctors recommend decreasing the dosage of injectables to 100-150 mg every two weeks for those trans men whose ovaries are inactive, or who have had their ovaries removed. Again, this will vary from person to person.
There are a number of different types of injectable testosterone ; those available may differ depending on the country in which you reside. The drug names for the same ester of testosterone may also differ depending on the company who produces it. This is not an exhaustive list, though it does cover the main injectable forms of T which are used by trans men for testosterone therapy .
Finally, testosterone esters are typically suspended in either cottonseed oil or sesame seed oil. Some people find that they may have an allergic reaction to one of the oils, or they might find that their acne increases or decreases depending on the type of oil they use. Certain brand-name testosterone esters are mass produced using one oil or the other (as noted below), but by using a compounding pharmacy, you can have any testosterone ester suspended in your choice of oil (with a proper prescription).
Injectable esters commonly used for testosterone therapy:
Testosterone enanthate: Chemical formula C26H40O3
Testosterone enanthate is one of the main forms of testosterone prescribed to men in the United States. It is a slow-acting ester with a release time between 8-10 days. The name-brand of T-enanthate available in the United States is called "Delatestryl," which is suspended in sesame oil. Testosterone enanthate is typically injected anywhere between once every week to once every three weeks. Generic testosterone enanthate can also be obtained through a compounding pharmacy; such pharmacies can mix the enanthate in either sesame or cotton seed oil.
Testosterone cypionate: Chemical formula C27H40O3
Testosterone cypionate is the other main injectable form of testosterone prescribed tomen in the United States. It is a slow-acting ester with a release time between 8-10 days, similar to that of enanthate . The name-brand of T-cypionate available in the United States is called "Depo-Testosterone ," which is suspended in cottonseed oil. Testosterone cypionate is typically injected anywhere between once every week to once every three weeks. Generic testosterone cypionate can also be obtained through a compounding pharmacy; such pharmacies can mix the cypionate in either sesame or cotton seed oil.
Sustanon 100 or 250
"Sustanon " is the brand name for two formulas of injectable testosterone that contain a blend of esters. "Sustanon 100" contains three testosterone esters: testosterone propionate (C22H32O3), testosterone phenylpropionate (C28H36O3), and testosterone isocaproate (C25H3803). "Sustanon 250" contains four testosterone esters: testosterone propionate (C22H32O3), testosterone phenylpropionate (C28H36O3), testosterone isocaproate (C25H3803), and testosterone decanoate (C29H4603). Both formulas feature both fast-acting and slow-acting esters, and can be injected anywhere from once every week to once every four weeks. Sustanon is prescribed outside of the United States.
Other injectable esters of testosterone:
Testosterone propionate: Chemical formula C22H32O3
Testosterone propionate is a fast-acting ester with a release time of 3-4 days. To keep blood levels from fluctuating greatly, propionate is usually injected between one to three times a week. It is for this reason that it is not usually prescribed hormone therapy . Some users also report that propionate is a more painful injection , with swelling and noticeable pain around the injection site. Brand names of testosterone propionate include "Testovis" and "Virormone."
Testosterone phenylpropionate: Chemical formula C28H36O3
Testosterone phenylpropionate is a slow-acting ester, with a release time of 1-3 weeks. A popular name brand for T-phenylpropionate is "Testolent ." Testosterone phenylpropionate is also one of the components of Sustanon and Omnadren .
Omnadren
"Omnadren " is the brand name for a blend of four testosterone esters: testosterone propionate (C22H32O3), testosterone phenylpropionate (C28H36O3), testosterone isocaproate (C25H3803), and testosterone decanoate (C29H4603). In the past, Omnadren consisted of a blend of different esters, but now is essentially the same formula as Sustanon , mentioned above. It features both fast-acting and slow-acting esters, and can be injected anywhere from once every week to once every four weeks. It is sometimes prescribed in parts of Europe.
Aqueous testosterone suspension
In the United States, injectable aqueous (non-esterified) testosterone is available, but it is very short-acting (it is completely released in the system within a matter of hours). Therefore, it is not typically used for men in transition, as it would require constant re-injection to maintain regular blood levels. The brand name for aqueous testosterone suspension is "Aquaviron."
Transdermal testosterone
The term "transdermal" refers to topical testosterone delivery through the skin, by the use of a patch, gel, or cream.
Transdermal testosterone is usually applied to the skin daily in small doses in an effort to keep a steady level of testosterone in the system at all times. This approach avoids the "peaks and valleys" in T-levels sometimes associated with injectable testosterone . With injectables, T levels can reach a low-point a few days before the next shot is due, which can cause irritability, hot flashes, and low energy in some users. Daily transdermal application can help alleviate such problems. Indeed, some men who regularly use injectable testosterone sometimes supplement with a gel or patch during the last few days of their dosing cycle to maintain their T levels.
Transdermal application is also attractive to those individuals who are not comfortable with needles and injections .
However, there are some disadvantages to transdermal delivery. Some forms of daily transdermal testosterone application, particularly the patch, are substantially more expensive than injectable testosterone . Testosterone patches often cause skin irritation and/or allergic reactions to users. They can fall off with excessive sweating, and they must be fully protected with plastic when swimming. Testosterone cream and gel can be transferred by direct skin contact with a partner; special care must be taken with female partners who wish to avoid potential virilization.
Testosterone patches
There are currently two brand-name testosterone patches available in the United States: "Androderm" and "Testoderm." (Note that there are two forms of Testoderm available: a scrotal patch and a non-scrotal patch. The non-scrotal patch, "Testoderm TTS," is described herein). Generic testosterone patches are not yet available. Both Androderm and Testoderm TTS are very fast-acting once they have permeated the skin. The testosterone in the patches is suspended in an alcohol-based gel.
In order to deliver the testosterone efficiently into the body, chemical enhancers are added to the patch to increase permeability of the skin. It is these enhancers that are often the cause of skin irritation in many users. Some individuals find Testoderm TTS to be less irritating to the skin than Androderm, but this will vary from person to person.
Androderm
Androderm patches come in two doses: 2.5 mg/patch and 5.0 mg/patch. The actual amount of testosterone in the 2.5 mg patch is 12.2 mg, and the actual amount in the 5.0 mg patch is 24.3 mg. The reason is that much of the testosterone in the patch will not manage to get into the system. So, for example, the aim of the 2.5 mg patch is to get about 2.5 mg successfully into the bloodstream per day. Therefore, it is possible to absorb slightly more or slightly less than the 2.5 mg of the patch's ideal dosage (the same reasoning, of course, applies to the 5.0 mg patch as well).
Androderm patches are usually applied on the back, abdomen, thighs, or upper arms. Because the active area of the patch is covered, the wearer does not have to worry about skin contact with a partner. Dosages will vary between 2.5 mg - 10 mg daily, by applying a single patch or combination of patches. As with any form of testosterone , dosage should be determined by your overall health, your testosterone levels as checked by your doctor, and your progress in masculinization.
Testoderm TTS
There are two types of Testoderm patches: one is intended for scrotal application, and one for application on other areas of the body. Testoderm TTS refers to the non-scrotal version of the patch-- this is the patch that should be used by men.
Testoderm TTS patches come in two doses: 4.0 mg/patch and 6.0 mg/patch. As with Androderm, the actual amount of testosterone in these patches is greater than the listed dose. The reason is the same as explained above in the Androderm section.
Testoderm TTS patches are usually applied on the back, abdomen, thighs, or upper arms. Because the active area of the patch is covered, the wearer does not have to worry about skin contact with a partner. Dosages will vary between 4.0 mg - 10 mg daily, by applying a single patch or combination of patches. As with any form of testosterone , dosage should be determined by your overall health, your testosterone levels as checked by your doctor.
Testosterone gel and cream
There are currently two brand-name versions of testosterone gel available in the United States: Androgel and Testim. There are no brand-name testosterone creams at this time. Both cream and gel formulations of testosterone can be made by compounding pharmacies. (For more information about compounding pharmacies, click here.) Gel formulations of testosterone are typically alcohol-based, whereas creams are typically safflower oil-based. The testosterone in creams and gels is typically very fast-acting once absorbed through the skin. Thus, it must be applied once or twice daily to maintain T levels.
Creams and gels are applied directly onto the skin. Care must be taken to avoid skin-to-skin contact with a partner on the site of application. Transfer of the testosterone from the site can be prevented by keeping the area covered.
Androgel
Androgel is a clear, alcohol-based gel that contains 1% non-esterified testosterone . It is very fast-acting once it has been absorbed by the skin, and so must be applied 1-2 times daily to maintain T levels. It is available in either unit-dose packets or multiple-dose pumps. The unit dose packets contain either 25 mg or 50 mg of testosterone . Approximately 10% of the applied testosterone from the packets is absorbed into the system, resulting in an effective dose of 2.5 mg or 5.0 mg, respectively.
Androgel should be applied to clean, dry skin and should not be applied to the genital area. Application sites should be allowed to dry for a few minutes prior to dressing. Hands should be washed thoroughly with soap and water after application.
In order to prevent transfer to another person, clothing should be worn to cover the application sites. If direct skin-to-skin contact with another person is anticipated, the application sites should be washed thoroughly with soap and water. Users should wait at least 2 hours after applying before showering or swimming; for optimal absorption, it may be best to wait 5-6 hours.
Testim
Testim, like Androgel , is a clear, alcohol-based gel that contains 1% non-esterified testosterone . It is very fast-acting once it has been absorbed by the skin, and so must be applied 1-2 times daily to maintain T levels. It is available in 5.0g unit-dose tubes. A 5.0g unit dose tube contains 50 mg of testosterone . Approximately 10% of the applied testosterone from the tube is absorbed into the system, resulting in an effective dose of 5.0 mg.
Testim should be applied to clean, dry skin-- preferably to the shoulders and/or upper arms. It should not be applied to the genitals or to the abdomen. Application sites should be allowed to dry for a few minutes prior to dressing. Hands should be washed thoroughly with soap and water after application.
In order to prevent transfer to another person, clothing should be worn to cover the application sites. If direct skin-to-skin contact with another person is anticipated, the application sites should be washed thoroughly with soap and water. Users should wait at least 2 hours after applying before showering or swimming; for optimal absorption, it may be best to wait 5-6 hours.
Compounded creams and gels
Compounded creams and gels can be mixed by compounding pharmacies, and are similar in dosing, application, and precautions to what is described above for Androgel and Testim.
There are two advantages of using compounding pharmacies for testosterone gel or cream. The first is cost: until a generic version of the gel is available, compounded gel will usually be the cheaper alternative. The second is customization: your doctor can write a prescription of varying concentration for gels or creams.
Oral testosterone
Methyltestosterone (C-17 alpha methylated testosterone )
Methyltestosterone is one of the earliest available oral testosterones. Its chemical structure is the hormone testosterone with an added methyl group at the c-17 alpha position of the molecule. The use of oral c-17 alpha methylated testosterone for masculinization is obsolete due to its toxicity to the liver. As such, methyltestosterone is not recommended for FTM hormone therapy . Brand names include "Metesto," "Methitest," "Testred," "Oreton Methyl," and "Android."
Testosterone undecanoate
Testosterone undecanoate is not a c-17 alpha alkylated hormone . Therefore, it is considered a safer oral form of testosterone . It is designed to be absorbed through the small intestine into the lymphatic system, posing less burden on the liver. Brand names for testosterone undecanoate include "Andriol ," "Androxon," "Understor," "Restandol," and "Restinsol." It is not available in the United States.
One disadvantage of orally administered undecanoate is that it is eliminated from the body very quickly, usually in 3-4 hours. Thus, frequent administration is necessary-- usually between 3-6 capsules a day. This can prove to be expensive when compared to injectable testosterone .
Sublingual/buccal testosterone
Sublingual and buccal testosterone delivery works by either placing a dissolving tablet under your tongue (sublingual) or by placing a tablet against the surface of the gums (buccal). It is different from oral delivery in that very little of the substance is swallowed, avoiding potential liver toxicity.
Sublingual
Sublingual testosterone can be obtained through compounding pharmacies. (For more information about compounding pharmacies, click here.)
Buccal
In 2003, the FDA approved a sustained-release buccal testosterone tablet called "Striant." It acts by adhering to the buccal mucosa (the small depression in the mouth where the gum meets the upper lip above the incisor teeth). Once applied, the tablet softens and delivers testosterone through the buccal mucosa, where it is then absorbed directly into the bloodstream, bypassing the gastrointestinal system and liver.
The recommended dosage for Striant is to replace the tablet about every 12 hours, though a different dosing schedule or number of tablets might be required depending on the needs of the patient.
Subcutaneous testosterone pellet
Another relatively new form of testosterone delivery is via a pellet of pure, crystalline testosterone implanted beneath the skin. The pellets are about the size of a grain of rice, and are typically placed in the buttocks or abdomen. The insertion of the pellets is a quick procedure, usually done under local anesthesia. Pellets are typically replaced after 3-4 months. "Testopel" is a brand name for testosterone pellets in the United States.
A 200 mg testosterone pellet releases testosterone at a steady rate of 1-3 mg per day. Several pellets can be inserted at the same time to increase dosage.
Some users have reported problems with the pellets working their way out from under the skin.
Overview
In testosterone therapy , testosterone (often called "T" for short) can be administered into the body in a number of ways. The most common method is intramuscular (IM) injection with a syringe. Other delivery methods include transdermal application through gel, cream, or patch applied to the skin; orally by swallowing tablets (this method is uncommon as it has been shown to have negative effects on the liver); sublingually/buccally by dissolving a tablet under the tongue or against the gums; or by a pellet inserted under the skin. The T-delivery method used will depend on the type of medication available in the country of treatment, the health risks/benefits for the patient of the delivery method in question, personal preference, and cost.
Testosterone is not stored by the body for future use, so in order to maintain healthy levels, it must be administered in timed intervals, and in appropriate dosages. Injectable and subcutaneous T pellets remain active in the body the longest. Injectable T is typically administered between once a week to once every three weeks, and subcutaneous T pellets are replaced every 3-4 months. Transdermal T (patch, gel, or cream) is typically applied to the skin in smaller daily doses; oral and sublingual/buccal T are also typically taken daily.
"Normal" testosterone Levels
An individual's testosterone levels are usually confirmed through a blood test called a "serum total testosterone test ." Testosterone exists in your bloodstream in two forms-- "bound" testosterone and "free" testosterone . The majority of bound testosterone in the body is chemically bound to a protein called "sex hormone binding globulin" (SHBG). The remaining bound testosterone in the system is mostly bound to albumin, another protein . Free testosterone is considered the "active" form of testosterone , as it is not chemically attached to any proteins; thus, it is readily available to bind to androgen receptor sites on cells.
A serum total testosterone test measures the total of these two forms of T. What are considered normal test levels of combined bound and free testosterone in male bodies can range anywhere from 300-1100 ng/dl (nanograms per deciliter). Levels will vary with age and individual factors.
It is useful to also measure the level of free testosterone in the system, as this may be more indicative of how hormone therapy is progressing. Levels of free testosterone can range between 0.3%-5% of the total testosterone count, with about 2% considered an optimal level. Ask your doctor to check for both total and free levels of testosterone in your system.
A note of caution about greatly increasing your T dosage
During the first months of T therapy, many men feel impatient waiting for changes to happen. Some may consider doubling or tripling their dose, thinking that the more they put in, the faster the changes will come. However, dramatically increasing your dose might have the effect of slowing your changes. This is because excess testosterone in your body can be converted into estrogen by an enzyme called "aromatase." This conversion is part of the body's natural feedback system-- if there is an abundance of testosterone in the body, it is converted ("aromatized") to estrogen in order to maintain a "normal" hormonal balance. Therefore, taking very large doses of testosterone might not be a great idea. Be patient; if you are not seeing results in a reasonable period of time, and/or your T levels are low, discuss modifying your dosage with your doctor.
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 repla***ent 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 prescribed for men in transition.
Testosterone delivery methods
Injectable testosterone
The dosage amount and timing for injectable testosterone will depend largely upon which ester is being used, as well as the individual's own response to the hormone . In general, dosages will vary between 50 mg and 300 mg per injection , depending on the ester and the dosing regimen. An average injectable dose is about 200-250 mg every two weeks, though many trans men inject 100 mg every week or every 10 days, or other variations depending on their own bodies' needs and sensitivities. Again, the exact dosage required will vary from person to person, and health and well-being should be carefully monitored while determining an individual's ideal dose.
Some doctors recommend decreasing the dosage of injectables to 100-150 mg every two weeks for those trans men whose ovaries are inactive, or who have had their ovaries removed. Again, this will vary from person to person.
There are a number of different types of injectable testosterone ; those available may differ depending on the country in which you reside. The drug names for the same ester of testosterone may also differ depending on the company who produces it. This is not an exhaustive list, though it does cover the main injectable forms of T which are used by trans men for testosterone therapy .
Finally, testosterone esters are typically suspended in either cottonseed oil or sesame seed oil. Some people find that they may have an allergic reaction to one of the oils, or they might find that their acne increases or decreases depending on the type of oil they use. Certain brand-name testosterone esters are mass produced using one oil or the other (as noted below), but by using a compounding pharmacy, you can have any testosterone ester suspended in your choice of oil (with a proper prescription).
Injectable esters commonly used for testosterone therapy:
Testosterone enanthate: Chemical formula C26H40O3
Testosterone enanthate is one of the main forms of testosterone prescribed to men in the United States. It is a slow-acting ester with a release time between 8-10 days. The name-brand of T-enanthate available in the United States is called "Delatestryl," which is suspended in sesame oil. Testosterone enanthate is typically injected anywhere between once every week to once every three weeks. Generic testosterone enanthate can also be obtained through a compounding pharmacy; such pharmacies can mix the enanthate in either sesame or cotton seed oil.
Testosterone cypionate: Chemical formula C27H40O3
Testosterone cypionate is the other main injectable form of testosterone prescribed tomen in the United States. It is a slow-acting ester with a release time between 8-10 days, similar to that of enanthate . The name-brand of T-cypionate available in the United States is called "Depo-Testosterone ," which is suspended in cottonseed oil. Testosterone cypionate is typically injected anywhere between once every week to once every three weeks. Generic testosterone cypionate can also be obtained through a compounding pharmacy; such pharmacies can mix the cypionate in either sesame or cotton seed oil.
Sustanon 100 or 250
"Sustanon " is the brand name for two formulas of injectable testosterone that contain a blend of esters. "Sustanon 100" contains three testosterone esters: testosterone propionate (C22H32O3), testosterone phenylpropionate (C28H36O3), and testosterone isocaproate (C25H3803). "Sustanon 250" contains four testosterone esters: testosterone propionate (C22H32O3), testosterone phenylpropionate (C28H36O3), testosterone isocaproate (C25H3803), and testosterone decanoate (C29H4603). Both formulas feature both fast-acting and slow-acting esters, and can be injected anywhere from once every week to once every four weeks. Sustanon is prescribed outside of the United States.
Other injectable esters of testosterone:
Testosterone propionate: Chemical formula C22H32O3
Testosterone propionate is a fast-acting ester with a release time of 3-4 days. To keep blood levels from fluctuating greatly, propionate is usually injected between one to three times a week. It is for this reason that it is not usually prescribed hormone therapy . Some users also report that propionate is a more painful injection , with swelling and noticeable pain around the injection site. Brand names of testosterone propionate include "Testovis" and "Virormone."
Testosterone phenylpropionate: Chemical formula C28H36O3
Testosterone phenylpropionate is a slow-acting ester, with a release time of 1-3 weeks. A popular name brand for T-phenylpropionate is "Testolent ." Testosterone phenylpropionate is also one of the components of Sustanon and Omnadren .
Omnadren
"Omnadren " is the brand name for a blend of four testosterone esters: testosterone propionate (C22H32O3), testosterone phenylpropionate (C28H36O3), testosterone isocaproate (C25H3803), and testosterone decanoate (C29H4603). In the past, Omnadren consisted of a blend of different esters, but now is essentially the same formula as Sustanon , mentioned above. It features both fast-acting and slow-acting esters, and can be injected anywhere from once every week to once every four weeks. It is sometimes prescribed in parts of Europe.
Aqueous testosterone suspension
In the United States, injectable aqueous (non-esterified) testosterone is available, but it is very short-acting (it is completely released in the system within a matter of hours). Therefore, it is not typically used for men in transition, as it would require constant re-injection to maintain regular blood levels. The brand name for aqueous testosterone suspension is "Aquaviron."
Transdermal testosterone
The term "transdermal" refers to topical testosterone delivery through the skin, by the use of a patch, gel, or cream.
Transdermal testosterone is usually applied to the skin daily in small doses in an effort to keep a steady level of testosterone in the system at all times. This approach avoids the "peaks and valleys" in T-levels sometimes associated with injectable testosterone . With injectables, T levels can reach a low-point a few days before the next shot is due, which can cause irritability, hot flashes, and low energy in some users. Daily transdermal application can help alleviate such problems. Indeed, some men who regularly use injectable testosterone sometimes supplement with a gel or patch during the last few days of their dosing cycle to maintain their T levels.
Transdermal application is also attractive to those individuals who are not comfortable with needles and injections .
However, there are some disadvantages to transdermal delivery. Some forms of daily transdermal testosterone application, particularly the patch, are substantially more expensive than injectable testosterone . Testosterone patches often cause skin irritation and/or allergic reactions to users. They can fall off with excessive sweating, and they must be fully protected with plastic when swimming. Testosterone cream and gel can be transferred by direct skin contact with a partner; special care must be taken with female partners who wish to avoid potential virilization.
Testosterone patches
There are currently two brand-name testosterone patches available in the United States: "Androderm" and "Testoderm." (Note that there are two forms of Testoderm available: a scrotal patch and a non-scrotal patch. The non-scrotal patch, "Testoderm TTS," is described herein). Generic testosterone patches are not yet available. Both Androderm and Testoderm TTS are very fast-acting once they have permeated the skin. The testosterone in the patches is suspended in an alcohol-based gel.
In order to deliver the testosterone efficiently into the body, chemical enhancers are added to the patch to increase permeability of the skin. It is these enhancers that are often the cause of skin irritation in many users. Some individuals find Testoderm TTS to be less irritating to the skin than Androderm, but this will vary from person to person.
Androderm
Androderm patches come in two doses: 2.5 mg/patch and 5.0 mg/patch. The actual amount of testosterone in the 2.5 mg patch is 12.2 mg, and the actual amount in the 5.0 mg patch is 24.3 mg. The reason is that much of the testosterone in the patch will not manage to get into the system. So, for example, the aim of the 2.5 mg patch is to get about 2.5 mg successfully into the bloodstream per day. Therefore, it is possible to absorb slightly more or slightly less than the 2.5 mg of the patch's ideal dosage (the same reasoning, of course, applies to the 5.0 mg patch as well).
Androderm patches are usually applied on the back, abdomen, thighs, or upper arms. Because the active area of the patch is covered, the wearer does not have to worry about skin contact with a partner. Dosages will vary between 2.5 mg - 10 mg daily, by applying a single patch or combination of patches. As with any form of testosterone , dosage should be determined by your overall health, your testosterone levels as checked by your doctor, and your progress in masculinization.
Testoderm TTS
There are two types of Testoderm patches: one is intended for scrotal application, and one for application on other areas of the body. Testoderm TTS refers to the non-scrotal version of the patch-- this is the patch that should be used by men.
Testoderm TTS patches come in two doses: 4.0 mg/patch and 6.0 mg/patch. As with Androderm, the actual amount of testosterone in these patches is greater than the listed dose. The reason is the same as explained above in the Androderm section.
Testoderm TTS patches are usually applied on the back, abdomen, thighs, or upper arms. Because the active area of the patch is covered, the wearer does not have to worry about skin contact with a partner. Dosages will vary between 4.0 mg - 10 mg daily, by applying a single patch or combination of patches. As with any form of testosterone , dosage should be determined by your overall health, your testosterone levels as checked by your doctor.
Testosterone gel and cream
There are currently two brand-name versions of testosterone gel available in the United States: Androgel and Testim. There are no brand-name testosterone creams at this time. Both cream and gel formulations of testosterone can be made by compounding pharmacies. (For more information about compounding pharmacies, click here.) Gel formulations of testosterone are typically alcohol-based, whereas creams are typically safflower oil-based. The testosterone in creams and gels is typically very fast-acting once absorbed through the skin. Thus, it must be applied once or twice daily to maintain T levels.
Creams and gels are applied directly onto the skin. Care must be taken to avoid skin-to-skin contact with a partner on the site of application. Transfer of the testosterone from the site can be prevented by keeping the area covered.
Androgel
Androgel is a clear, alcohol-based gel that contains 1% non-esterified testosterone . It is very fast-acting once it has been absorbed by the skin, and so must be applied 1-2 times daily to maintain T levels. It is available in either unit-dose packets or multiple-dose pumps. The unit dose packets contain either 25 mg or 50 mg of testosterone . Approximately 10% of the applied testosterone from the packets is absorbed into the system, resulting in an effective dose of 2.5 mg or 5.0 mg, respectively.
Androgel should be applied to clean, dry skin and should not be applied to the genital area. Application sites should be allowed to dry for a few minutes prior to dressing. Hands should be washed thoroughly with soap and water after application.
In order to prevent transfer to another person, clothing should be worn to cover the application sites. If direct skin-to-skin contact with another person is anticipated, the application sites should be washed thoroughly with soap and water. Users should wait at least 2 hours after applying before showering or swimming; for optimal absorption, it may be best to wait 5-6 hours.
Testim
Testim, like Androgel , is a clear, alcohol-based gel that contains 1% non-esterified testosterone . It is very fast-acting once it has been absorbed by the skin, and so must be applied 1-2 times daily to maintain T levels. It is available in 5.0g unit-dose tubes. A 5.0g unit dose tube contains 50 mg of testosterone . Approximately 10% of the applied testosterone from the tube is absorbed into the system, resulting in an effective dose of 5.0 mg.
Testim should be applied to clean, dry skin-- preferably to the shoulders and/or upper arms. It should not be applied to the genitals or to the abdomen. Application sites should be allowed to dry for a few minutes prior to dressing. Hands should be washed thoroughly with soap and water after application.
In order to prevent transfer to another person, clothing should be worn to cover the application sites. If direct skin-to-skin contact with another person is anticipated, the application sites should be washed thoroughly with soap and water. Users should wait at least 2 hours after applying before showering or swimming; for optimal absorption, it may be best to wait 5-6 hours.
Compounded creams and gels
Compounded creams and gels can be mixed by compounding pharmacies, and are similar in dosing, application, and precautions to what is described above for Androgel and Testim.
There are two advantages of using compounding pharmacies for testosterone gel or cream. The first is cost: until a generic version of the gel is available, compounded gel will usually be the cheaper alternative. The second is customization: your doctor can write a prescription of varying concentration for gels or creams.
Oral testosterone
Methyltestosterone (C-17 alpha methylated testosterone )
Methyltestosterone is one of the earliest available oral testosterones. Its chemical structure is the hormone testosterone with an added methyl group at the c-17 alpha position of the molecule. The use of oral c-17 alpha methylated testosterone for masculinization is obsolete due to its toxicity to the liver. As such, methyltestosterone is not recommended for FTM hormone therapy . Brand names include "Metesto," "Methitest," "Testred," "Oreton Methyl," and "Android."
Testosterone undecanoate
Testosterone undecanoate is not a c-17 alpha alkylated hormone . Therefore, it is considered a safer oral form of testosterone . It is designed to be absorbed through the small intestine into the lymphatic system, posing less burden on the liver. Brand names for testosterone undecanoate include "Andriol ," "Androxon," "Understor," "Restandol," and "Restinsol." It is not available in the United States.
One disadvantage of orally administered undecanoate is that it is eliminated from the body very quickly, usually in 3-4 hours. Thus, frequent administration is necessary-- usually between 3-6 capsules a day. This can prove to be expensive when compared to injectable testosterone .
Sublingual/buccal testosterone
Sublingual and buccal testosterone delivery works by either placing a dissolving tablet under your tongue (sublingual) or by placing a tablet against the surface of the gums (buccal). It is different from oral delivery in that very little of the substance is swallowed, avoiding potential liver toxicity.
Sublingual
Sublingual testosterone can be obtained through compounding pharmacies. (For more information about compounding pharmacies, click here.)
Buccal
In 2003, the FDA approved a sustained-release buccal testosterone tablet called "Striant." It acts by adhering to the buccal mucosa (the small depression in the mouth where the gum meets the upper lip above the incisor teeth). Once applied, the tablet softens and delivers testosterone through the buccal mucosa, where it is then absorbed directly into the bloodstream, bypassing the gastrointestinal system and liver.
The recommended dosage for Striant is to replace the tablet about every 12 hours, though a different dosing schedule or number of tablets might be required depending on the needs of the patient.
Subcutaneous testosterone pellet
Another relatively new form of testosterone delivery is via a pellet of pure, crystalline testosterone implanted beneath the skin. The pellets are about the size of a grain of rice, and are typically placed in the buttocks or abdomen. The insertion of the pellets is a quick procedure, usually done under local anesthesia. Pellets are typically replaced after 3-4 months. "Testopel" is a brand name for testosterone pellets in the United States.
A 200 mg testosterone pellet releases testosterone at a steady rate of 1-3 mg per day. Several pellets can be inserted at the same time to increase dosage.
Some users have reported problems with the pellets working their way out from under the skin.
