A common question we always get asked about testosterone and testosterone injections is the following

"Why do I need to inject testosterone, can't I just make it in pill form?".

The answer to this question lies in the chemistry of testosterone, and in order for the reader to fully understand why testosterone injections are best and their other limitations, we need to recount some history.

Before we get into the chemistry and the history behind it, it's important to understand that there is indeed testosterone in pill or capsule form that can be taken orally.

In addition to testosterone injections, there are other delivery methods such as transdermal patches, gels, and creams.

The problem with oral testosterone is that, for starters, certain oral forms (methyltestosterone) exhibit some degree of hepatotoxicity (liver toxicity) in the body when ingested.

While studies have demonstrated that it does not cause serious problems when administered in the proper doses, it is impractical to use for medical purposes that require long-term administration, such as testosterone replacement therapy (TRT).

Methyltestosterone and other methylated (also known as C17-alpha alkylated) oral anabolic steroids should not be administered for extended periods of time (8 weeks or more on average) without concern for liver stress and toxicity.

Testosterone injections do not have this problem because they do not negatively affect the liver.

The second oral form of testosterone, Andriol (testosterone undecanoate), utilizes a system in which testosterone is ester-bound to a highly fat-soluble carboxylic acid (undecanoic acid).

High fat solubility means that the testosterone travels further down the gastrointestinal tract and is absorbed into the lymphatic system.

The advantage of andriol over methyltestosterone is that andriol is not C17-alpha alkylated and is therefore not hepatotoxic, but the disadvantages of andriol are that it is very poorly absorbed, has very low bioavailability, and is very expensive.

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Testosterone injections completely bypass the disadvantages of the gastrointestinal tract, bypassing the first pass through the liver (where the hormone is metabolized into inactive metabolites before reaching the bloodstream) and absorption problems in the lymphatic system.

With injections, the potency and loss of the hormone is minimized, and the accuracy of the dose and release time can be better controlled.

Becoming more popular in recent years are topical applications such as transdermal gels, creams, and patches.

They are popular not only because they are more cost-effective and efficient than oral formulations, but also because of the convenience of their ease of use.

These products are topical solutions or patches containing testosterone, which are rubbed into the skin to be absorbed through the skin.

Like testosterone injections, they avoid gastrointestinal restrictions, but there are concerns about absorption and the inconvenience of transdermal application.

Other concerns include the possibility of the cream or gel getting on other clothes, bed sheets, or people (such as close contact with a wife, girlfriend, or child), which can be uncomfortable, and the fact that some gels and creams wash off or wash away easily if you sweat heavily or spray with water.

Of course, these are issues unrelated to testosterone injections.

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History of Testosterone and Chemical Modifications for Oral and Injectable Testosterone

Testosterone was first officially discovered, isolated, and synthesized in the lab in the 1930s by German scientist Adolf Butenant and his colleagues.

When this organic compound was first investigated, the scientific and medical communities were amazed, and its potential and uses were just beginning to be understood.

However, the initial testing and discovery of testosterone had some limitations. Of course, injecting testosterone was the only viable method of administration when it was first discovered.

This is because, as mentioned earlier, testosterone is quickly and efficiently metabolized by enzymes in the liver into chemically inactive metabolites that are excreted out of the body in the urine and feces.

Not all orally ingested testosterone succumbs to this fate, but only a fraction of it makes it intact into the bloodstream.

Another problem is one that plagues testosterone injections themselves. Testosterone has a very short half-life before it is metabolized and eliminated from the body, which makes it very inconvenient to use for medical purposes because in its pure form (testosterone suspension) it must be injected daily or several times a day.

For those unfamiliar with the term 'half-life', it is a scientific and medical term used to describe the time required for the original dose of an administered substance to be reduced to half of its original dose in the human body. This is a very important term and definition to remember throughout this article, and will help you understand testosterone injections.

For example, if testosterone propionate has a half-life of 4.5 days and you administered 100 mg on day 1, after 4.5 days, only 50 mg will be left in your body.

The aforementioned characteristics, properties, and characteristics of pure unchanged testosterone presented problems with regard to administration, as well as convenience of administration.

The first testosterone products designed to be administered by injection were known as testosterone suspensions.

Testosterone suspension is just a microcrystalline form of testosterone suspended in water, and requires shaking the vial to evenly disperse the microcrystals before injection.

Aside from the problem of having an unrealistic and inconvenient half-life for testosterone, testosterone suspension is also very painful to inject because of the crystals and requires a large needle gauge.

At this point, it became clear that testosterone needed to be modified in some way to find a suitable form that would be convenient to administer as well as an oral testosterone injectable.

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The first attempt at oral testosterone was methyltestosterone, which methylated testosterone at the 17th carbon (also known as C17-alpha alkylation).

This made testosterone more bioavailable through oral ingestion, but as mentioned earlier in this article, it was impractical for long-term therapeutic use due to its hepatotoxicity.

To make testosterone injections more tolerable and practical, testosterone was modified by adding a carboxylic acid to the 17th carbon of its steroidal structure.

There are several different carboxylic acids of different lengths, some shorter than others and some longer.

The longer the carboxylic acid, the longer the half-life of the attached hormone.

The carboxylic acid attaches to the 17th carbon of testosterone via an ester bond, creating an esterified variant of testosterone.

For example, ester bonding of enanthoic acid to testosterone produces testosterone enanthate.

When propanoic acid is esterified to testosterone, it produces testosterone propionate, and so on.

Esterification creates an injectable form of testosterone that makes testosterone injections much more comfortable and convenient.

Esterification does not change the pharmacologic effects of testosterone (or hormones combined with testosterone) on the body, but it does increase the half-life and release rate of the hormone in the body. For example, when testosterone enanthate is injected into the body, the body's esterase enzymes in the bloodstream and liver work to separate the enanthate ester from the testosterone molecule, leaving only pure testosterone to perform its functions in the body.

Testosterone cannot perform its function until this ester is separated from the hormone, which takes a variable amount of time depending on the type of ester.

For example, testosterone enanthate has a half-life of 7 to 10 days, testosterone propionate is 4.5 days, and testosterone cypionate is 10 to 12 days.

Therefore, depending on the esterified testosterone variant chosen, users can administer testosterone injections less frequently, making administration much more convenient, comfortable, and practical.

For example, testosterone enanthate only needs to be administered once or twice a week (ideally) for athletic performance enhancement purposes. In the case of medical TRT, doctors and healthcare professionals may administer/recommend once a week or every two weeks.

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Medical and Non-Medical Uses of Testosterone Injections (Athletic Performance Enhancement)

Testosterone is one of the most widely and extensively used anabolic steroids, especially since scientific advances over the years have modified the form of testosterone injections to make them more convenient and comfortable to administer.

Using testosterone injections in a medical and clinical setting can be quite different from using them in a bodybuilding, athletic, and physique/performance enhancement setting.

Testosterone (and its synthetic derivatives) is a very important medication in the medical setting, and is considered a high safety, low risk drug.

This can be easily seen by looking at how widely testosterone is used in medicine, and how often it is used and prescribed to alleviate, treat, or cure a variety of debilitating conditions and diseases.

Testosterone itself is the primary use of testosterone replacement therapy (TRT) in medicine. It is probably the only use of testosterone today.

It can also be used for other purposes, such as recovery of burn victims, trauma patients, recovery from surgery, wasting diseases, and other debilitating conditions, but these are primarily reserved for the application of TRT and transgender hormone therapy.

Other debilitating conditions and diseases may be better treated with other synthetic analogs of testosterone, which have been modified in various ways to make them less prone to certain side effects in patients or have the ability to be administered to user groups that traditionally do not tolerate testosterone well (such as women and children).

For these uses, various modified analogs and derivatives of testosterone are more suitable than testosterone itself.

For medical uses of testosterone injections, the doses used and the frequency of administration are lower and less frequent than for athletic performance and physique enhancement.

For example, in the case of TRT, testosterone is typically administered via testosterone injections (although transdermal creams, gels, and patches are beginning to grow in popularity), and the doses administered are intended only to restore testosterone levels to the normal range in men who have been determined to be hypogonadal.

This treatment typically involves administering testosterone injections once a week at a dose of 100 to 250 mg per week (testosterone enanthate is commonly used).

It is up to the doctor's discretion whether the testosterone injections are administered by the doctor or whether the patient is allowed to self-administer them at home.

Typically, patients are taught how to self-medicate so they don't have to visit the doctor as often to get testosterone injections, which is more convenient.

Some doctors may prescribe less frequent injections, such as a single 250 mg injection every two weeks (testosterone enanthate, testosterone cypionate, or sustanon 250 are commonly used).

The number and dose of injections is usually determined by monitoring the individual's testosterone levels through regular blood tests and pinpointing the exact range of desired testosterone levels, adjusting the dose and frequency of injections accordingly.

Other medical uses for which testosterone is actually used (e.g., wasting diseases) may require a different dose and frequency of administration than TRT.

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When the goal is to enhance athletic performance and physique, the administration and dosage protocol changes significantly.

Since the goal is no longer to restore normal physiologic levels (instead, it is used to increase muscle mass and athletic performance), higher (supraphysiologic) doses and more frequent injections are required to optimally maintain plasma peaks of the hormone.

While TRT patients don't have to worry about improving their performance on a weekly (or even daily) basis, athletes and bodybuilders do.

The human body produces about 70 mg of testosterone per week, but the doses needed to improve athletic performance are much higher than this, with beginners taking at least 300 to 500 mg per week and some advanced bodybuilders and steroid users taking more than 1,000 mg per week (although rare, there have been actual reports). In addition to high doses, testosterone injections must be administered more frequently.

While TRT patients can get away with injecting 250 mg of testosterone enanthate once a week or once every two weeks, athletes and bodybuilders need to inject 250 mg of testosterone enanthate twice a week (500 mg total) to consistently experience the benefits of enhanced athletic performance and physique.

The reason for this is that peak plasma concentrations of the hormone must remain constant for sustained biological action on muscle tissue when athletic performance and physique enhancement is desired.

For medical purposes, such as TRT, rapid spikes and dips in plasma levels can be tolerated because the user is using testosterone injections to achieve a 'normal' state of health and is not particularly concerned with significant or dramatic gains in muscle mass or strength from week to week.

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Testosterone Injection Side Effects

Another frequently asked question regarding testosterone injections is the side effects associated with testosterone injections. A general and comprehensive list of testosterone side effects can be found in our testosterone profiles (testosterone enanthate, testosterone cypionate, testosterone propionate) and testosterone articles, but here we'll take a quick look at how testosterone injection side effects can vary depending on the administration method and protocol.

Testosterone injection side effects can vary from individual to individual depending on the method of administration.

We've outlined the differences between testosterone injection administration related to athletic performance and physique enhancement and medical testosterone injection administration (primarily for TRT).

There are some important differences between the two, and the way individuals respond is also different. It is a well-known fact that rapid spikes and dips in plasma hormone levels can cause a variety of side effects to be much worse than when plasma hormone levels remain constant.

A characteristic of all testosterone injections, whether long-acting testosterone such as testosterone enanthate or short-acting testosterone such as testosterone propionate, is that plasma testosterone levels rise rapidly within the first day or a few days after administration.

However, this is followed by a very rapid decline in levels (this is why testosterone blends such as Sustanon 250 were originally formulated to best address this issue).

While hormone levels are rising rapidly and then falling rapidly, the incidence of side effects increases.

When testosterone injections are administered infrequently (e.g. once a week or every other week for testosterone enanthate), acne, oily skin, and various other androgenic side effects can increase.

Estrogen-related side effects due to increased aromatization caused by high and low plasma levels are also a frequent problem.

Testosterone, dihydrotestosterone, estrogen, and other hormones are constantly out of balance because the levels of testosterone itself often go up and down, throwing other hormones out of balance.

The best solution to this problem, and the best way to reduce the incidence of testosterone injection side effects, is to administer more frequently.

The general rule here is to take into account the half-life of the type of testosterone being used and administer injections at half of that period.

For example, testosterone enanthate has a half-life of about 7 to 10 days, meaning that it should ideally be administered every 3 to 4 days to maintain more stable plasma levels (e.g., inject on Monday, then inject on Thursday). In the case of testosterone propionate, the half-life is 4.5 days.

Therefore, to maintain stable plasma levels, it should be administered at least every other day.

This will result in much more stable plasma levels than administering testosterone injections only on the last day of the half-life (e.g., 7 or 10 days for testosterone enanthate).

This protocol applies to both the medical application of TRT and the enhancement of athletic performance and physique.

This dosing protocol will significantly reduce the incidence of testosterone injection side effects and make the overall experience more comfortable for the user.