injection

Types of Testosterone

There are several possible ways of administering testosterone – through the skin (transdermal), orally, intramuscular (IM) injection and pellet implant.

Fig. 1 Chemical structure of Testosterone
Fig. 1 Chemical structure of Testosterone

Transdermal administration may mean either a gel or a patch. In Australia the gel is more common and is marketed as Testogel. The gel contains free testosterone (‘Free’ testosterone is simply testosterone that isn’t bound to anything – most of the testosterone in our bodies is bound to a protein called Sex Hormone Binding Globulin or SHBG if you see it on your blood work results). The testosterone in the gel is absorbed into your skin, which forms a temporary reservoir of testosterone, which then diffuses into your bloodstream over the next few hours.

Common dosages for the gel are 5 and 10 mg/day. Because only about 10% of testosterone delivered transdermally actually makes it into the bloodstream (the rest is washed/sweated off). 5 grams of gel actually contains 50mg testosterone.

Some problems associated with transdermal testosterone include skin irritation (mainly due to the absorption enhancers present in the gel/patch) and possible exposure to other people – the gel in particular can ‘rub off’ with close contact, such as an intimate partner. For males (identified ‘female’ at birth) who generally require serum testosterone levels in the higher end of the normal range to achieve sufficient masculinisation, the gel is often unable to deliver sufficient testosterone.

Testosterone is basically broken down by the liver and therefore the oral (by mouth) administration of testosterone is challenging. Many modified forms of testosterone have been trialled, but most are strongly toxic to the liver.

One ‘safe’ form of oral testosterone is testosterone undecanoate, which is sold in Australia as Andriol. Peak bloodstream concentration of testosterone occurs about four hours after each dose and most of the dose is eliminated in around eight hours. For this reason Andriol capsules are generally taken at least twice daily.

Testosterone injections contain testosterone esters, which are a simple derivative of testosterone. Sustanon250 contains four different ‘size’ esters – 30mg testosterone propionate, 60 mg testosterone isocaproate, 60mg testosterone phenylpropionate and 100mg testosterone decanoate. (Propionate = tiny, isocaproate = small, phenylpropionate = medium, decanoate = large). There is a total of 176mg free testosterone in each ml (the other 74mg are the ‘ester bits’).

Because testosterone is not easily soluble in oil, they make an ester of it by tacking on to some carbon chains which increase the oil solubility of testosterone (see the OH bit at the top of Fig.1). This works because oils are basically long carbon chains and “like dissolves like”. The esters aren’t all that stable and once injected, they hydrolyse (the tacked on bit falls off).

When this happens the free testosterone is no longer soluble in oil, but now it’s soluble in water. This free testosterone moves (migrates) to where water is – which happens to be your bloodstream (this is a good thing). The smaller the tacked on bit is, the faster it hydrolyses (breaks down in water).

The testosterone propionate takes around 3-4 days to do this, testosterone isocaproate takes about six days, testosterone phenylpropionate takes 9-10 days and testosterone decanoate takes around fourteen days. The longer the time, the more spread out the peak from that particular ester is.

Overall, what happens looks roughly like the following graph:

Fig 2: Approximate Testosterone levels after a Sustanon250 injection
Fig 2: Approximate Testosterone levels after a Sustanon250 injection

So at four days after an injection, your total testosterone (T) level is made up of mainly T-propionate, but a little bit of T-isocaproate. At seven days, the T-propionate has pretty much gone, your T level is made up of mostly T-isocaproate but a fair bit of T-phenylpropionate and a tiny bit of T-decanoate. At twelve days nearly all the T-isocaproate has hydrolysed and your T level is mainly made up of T-phenylpropionate and T-decanoate. After about two weeks, T-decanoate is all that is left. The ester bits and the oil are simply disposed of by your body.

Sustanon100 shots contain 20 mg T-propionate, 40 mg T-isocaproate, 40 mg T-phenylpropionate. As there is no long acting ester in Sustanon100 shots, they need to be given at a shorter interval, normally 8-10 days.

PrimotestonDepot is another injectable form of testosterone available in Australia. It contains 250mg of T-enanthalate and the dosage is similar to Sustanon250.

In 2006, a new form of injectable testosterone was approved in Australia. Reandron1000 contains 1000mg (i.e. 1 gram) of T-undecanoate (yep, the same stuff as in Andriol) in 4mL of oil. It is injected the same way as Sustanon or Primoteston, except usually more than one injection site is used and the 4mL is split between each site. Reandron injections generally last about 10-12 weeks. When you first begin Reandron injections, your second Reandron injection should be given at about six weeks in order to allow your body to ‘build up’ a baseline level of testosterone.

The absorption of Reandron occurs roughly like the following graph:

Fig 3: Approximate testosterone levels given by a Reandron1000 injection
Fig 3: Approximate testosterone levels given by  Reandron1000 injection

The final common form of testosterone administration is implanted pellets [Ed note: Pellets are no longer available in Australia]. The pellets are pure crystallised testosterone. They are implanted by your doctor under some fatty skin (not an insult!) The most common sites are the hip and the stomach. As blood washes over the pellets, the pellets gradually dissolve, releasing testosterone directly into your bloodstream. The blood concentration of testosterone will depend on the number of pellets implanted at one time. Pellets last 4-5 months regardless of how many are implanted at once.

The rate of testosterone release from pellets is generally quite steady, however when the pellets are near the end of their ‘life’, they often break up into many small pieces which release testosterone more effectively (because they have a larger surface area) leading to a temporary spike in testosterone levels immediately prior to the pellet being used up.

The most common risk with testosterone pellets is rejection of the pellet, which can be extruded through the skin. Some people are concerned that the testosterone in the injections is “modified”, “synthetic” or “not natural”. The fact is, all forms of testosterone that we can take have been processed in some way.

Testosterone in the injections is modified, by adding the “ester bit”, whereas the gel contains free testosterone, could be taken to mean that the gel is “more natural” but then the absorption enhancers in the gel certainly aren’t natural. Remember testosterone is poorly soluble in fat/oil? The absorption enhancers present in gel work by creating channels between fat cells for the testosterone to “burrow through” – not a very efficient process, which is why a 5mg patch actually contains 10x that. The absorption enhancers (the simplest one is ethanol – which is the same as alcohol in drinks) are also the main culprits in skin irritation.

Pellets contain pure testosterone. The process of crystallising the testosterone ensures its purity. The idea of taking one thing (in this case testosterone ester) into the body, when the actual drug is something else (in this case testosterone) is nothing new. Many drugs are converted to their active form once in they are put into the body. The stuff you take is called a pro-drug. Once the pro-drug is converted to its active form, it is a drug. For example, the well known cancer treatment cisplatin is a pro-drug.

The ‘more natural’ mentality is pseudoscience, whether it is applied to pharmaceuticals or food. There are many forms of testosterone in your body. So ask yourself, is the protein bound hormone less natural than the free form? (both are naturally present). All that matters for your body, is that adequate androgenisation (masculinising) is occurring, and all other parameters (cholesterol etc) are in order. Of course, regardless of where you are in transition, it’s a good idea to get your GP to check your cholesterol every six months or so.

Firstly a chemical (be it a food additive, a drug or something else) is the same chemical, regardless of whether it was isolated from a natural source (a plant or an animal) or whether it was manufactured by chemists. The testosterone in the gel, the pellets and the testosterone in the injections are all manufactured the same way. The T in the injections has one extra step (taking on the ester bits) which is undone by your body to be able to use the testosterone.

The scary stories surrounding exogenous (from outside the body) testosterone (eg ‘roid rage etc) are only relevant to men abusing testosterone, which does not include males (identified ‘female’ at birth) using testosterone to transition. When men who are abusing testosterone (for example, bodybuilders who often take in excess of 1000mg/week!) have problems (with ejaculation etc) this is because their natural testosterone production has decreased. A bodybuilder who is abusing testosterone, will lose much of their ability to produce testosterone, simply because they are feeding their body so much of the stuff that their body says, “Oh hey! I’ve got loads and loads of testosterone, I’d better not make any more” and once they stop taking testosterone their body takes some time to realise it doesn’t have huge amounts of T floating around and that it needs to wake up the machinery that normally makes T. In this way sometimes permanent damage is done.

In a similar way, a few months worth of T shots provides feedback to your brain and gonads (ovaries) telling them to stop your natural female hormone production. Any of your natural male hormone production is also altered. Remember you are overriding your body’s natural homeostasis (the body regulates itself such that everything is in equilibrium). After a shot, your body has stacks of T – so it doesn’t need to make any more. Although you don’t have much natural T production to start with! Yet, your injections more than make up for that.

If you have other questions about testosterone, please send them in and I’ll do my best to find answers for you and publish them on the website. Your GP should also be able to find answers for you.

Images from “Treatment of Male Hypogonadism With Testosterone Undecanoate Injected at Extended Intervals of 12 Weeks: A Phase II Study”, Journal of Andrology, Vol. 23, No. 3, May/June 2002.

Matt (2009). All about testosterone, Torque 9(2).

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