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Testosterone Ester Report
One of the most misunderstood subjects in the world of steroids is the ester--the mechanism by which injectable esterified steroids like testosterone cypionate, testosterone enanthate, and Sustanon work. If you take a quick look around the Internet you will probably find countless articles that consider one form of a steroid far more effective than another. Arguments over the superiority of cypionate to enanthate, or Sustanon to all other testosterones are of course very common. Such arguments are in all practicality, baseless. In this report we'll take an authoritative look at the ester and what specifically it does to a steroid.
WHAT AN ESTER IS, AND HOW IT WORKS
I'm sure that if you have taken an interest in anabolic steroids you have noticed the similarities on the labeling of many drugs. Let's look at testosterone for example. One can find compounds like testosterone cypionate, enanthate, propionate, heptylate; caproate, phenylpropionate, isocaproate, decanoate, acetate, the list goes on and on. In all such cases the parent hormone is testosterone, which had been modified by adding an ester (enanthate, propionate etc.) to its structure. The following question arises: What is the difference between the various esterified versions of testosterone in regards to their use in bodybuilding?
An ester is a chain composed primarily of carbon and hydrogen atoms. This chain is typically attached to the parent steroid hormone at the 17th carbon position (beta orientation), although some compounds do carry esters at position 3 (for the purposes of this article it is not crucial to understand the exact position of the ester). Esterification of an injectable anabolic/androgenic steroid basically accomplishes one thing, it slows the release of the parent steroid from the site of injection. This happens because the ester will notably lower the water solubility of the steroid, and increase its lipid (fat) solubility. This will cause the drug to form a deposit in the muscle tissue, from which it will slowly enter into circulation as it is picked up in small quantities by the blood. Generally, the longer the ester chain, the lower the water solubility of the compound, and the longer it will take to for the full dosage to reach general circulation.
Slowing the release of the parent steroid is a great benefit in steroid medicine, as free testosterone (or other steroid hormones) previously would remain active in the body for a very short period of time (typically hours). This would necessitate an unpleasant daily injection schedule if one wished to maintain a continuous elevation of testosterone (the goal of testosterone replacement therapy). By adding an ester, the patient can visit the doctor as infrequently as once per month for his injection, instead of having to constantly re-administer the drug to achieve a therapeutic effect. Clearly without the use of an ester, therapy with an injectable anabolic/androgen would be much more difficult.
Esterification temporarily deactivates the steroid molecule. With a chain blocking the 17th beta position, binding to the androgen receptor is not possible (it can exert no activity in the body). In order for the compound to become active the ester must therefore first be removed. This automatically occurs once the compound has filtered into blood circulation, where esterase enzymes quickly cleave off (hydrolyze) the ester chain. This will restore the necessary hydroxyl (OH) group at the 17th beta position, enabling the drug to attach to the appropriate receptor. Now and only now will the steroid be able to have an effect on skeletal muscle tissue. You can start to see why considering testosterone cypionate much more potent than enanthate makes little sense, as your muscles are seeing only free testosterone no matter what ester was used to deploy it.
ACTIONS OF DIFFERENT ESTERS
There are many different esters that are used with anabolic/androgenic steroids, but again, they all do basically the same thing. Esters vary only in their ability to reduce a steroid's water solubility. An ester like propionate for example will slow the release of a steroid for a few days, while the duration will be weeks with a decanoate ester. Esters have no effect on the tendency for the parent steroid to convert to estrogen or DHT (dihydrotestosterone: a more potent metabolite) nor will it effect the overall muscle-building potency of the compound. Any differences in results and side effects that may be noted by bodybuilders who have used various esterified versions of the same base steroid are just issues of timing. Testosterone enanthate causes estrogen related problems more readily than Sustanon, simply because with enanthate testosterone levels will peak and trough much sooner (1-2 week release duration as opposed to 3 or 4). Likewise testosterone suspension is the worst in regards to gyno and water bloat because blood hormone levels peak so quickly with this drug. Instead of waiting weeks for testosterone levels to rise to their highest point, here we are at most looking at a couple of days. Given an equal blood level of testosterone, there would be no difference in the rate of aromatization or DHT conversion between different esters. There is simply no mechanism for this to be possible.
There is however one way that we can say an ester does technically effect potency; it is calculated in the steroid weight. The heavier the ester chain, the greater is its percentage of the total weight. In the case of testosterone enanthate for example, 250mg of esterified steroid (testosterone enanthate) is equal to only 180mg of free testosterone. 70mgs out of each 250mg injection is the weight of the ester. If we wanted to be really picky, we could consider enanthate slightly MORE potent than cypionate (I know this goes against popular thinking) as its ester chain contains one less carbon atom (therefore taking up a slightly smaller percentage of total weight). Propionate would of course come out on top of the three, releasing a measurable (but not significant) amount more testosterone per injection than cypionate or enanthate.
IN CONCLUSION
While the advent of esters certainly constitutes an invaluable advance in the field of anabolic steroid medicine, clearly you can see that there is no magic involved here. Esters work in a well-understood and predictable manner, and do not alter the activity of the parent steroid in any way other than to delay its release. Although the lure surrounding various steroid products like testosterone cypionate, Sustanon, Omnadren etc. certainly makes for interesting conversation, realistically it just amounts to misinformation that the athlete would be better off ignoring. Testosterone is testosterone and anyone who is going to tell you one ester form of this (or any) hormone is much better than another one should do a little more research, and a lot less talking.
ESTER PROFILES
Sustanon: The "king" of testosterone blends.
The four different testosterone esters in this product certainly look appealing to the consumer, there is no denying that. But for the athlete I think it is all just a matter of marketing (Hell, why buy one ester when you can get four?). In clinical situations I can see some strong uses for it. If you were undergoing testosterone replacement therapy for example, you would probably find Sustanon a much more comfortable option than testosterone enanthate. You would need to visit the doctor less frequently for an injection, and blood levels should be more steadily maintained between treatments. But for the bodybuilder who is injecting 4 ampules of Sustanon per week, there is no advantage over other testosterone products. In fact, the high price tag for Sustanon usually makes it a very poor buy in the face of cheaper testosterone enanthate/cypionate. Bodybuilders should probably stop looking at the four ester issue, and stick with totals (Sustanon is just a 250mg testosterone ampule). Were enanthate to be available for say $10 per amp of 250mg, and Sustanon priced nearly double that, buying the Sustanon would be like throwing money away. If you could get nearly double the milligram amount for the same price with enanthate, this is the better product to go with hands down. Leave the high priced stuff for the guys who don't know any better.
Acetate: Chemical Structure C2H4O2.
Also referred to as Acetic Acid; Ethylic acid; Vinegar acid; vinegar; Methanecarboxylic acid. Acetate esters delay the release of a steroid for only a couple of days. Contrary to what you may have read, acetate esters do not increase the tendency for fat removal. Again, there is no known mechanism for it to do so. This ester is used on oral primobolan tablets (metenolone acetate), Finaplix (trenbolone acetate) implant pellets, and occasionally testosterone.
Propionate: Chemical Structure C3H6O2.
Also referred to as Carboxyethane; hydroacrylic acid; Methylacetic acid; Ethylformic acid; Ethanecarboxylic acid; metacetonic acid; pseudoacetic acid; Propionic Acid. Propionate esters will slow the release of a steroid for several days. To keep blood levels from fluctuating greatly, propionate compounds are usually injected two to three times weekly. Testosterone propionate and methandriol dipropionate (two separate propionate esters attached to the parent steroid methandriol) are popular items.
Phenylpropionate: Chemical Structure C9H10O2.
Also referred to as Propionic Acid Phenyl Ester. Phenylpropionate will extend the release of active steroid a few days longer than propionate. To keep blood levels even, injections are given at least twice weekly. Durabolin is the drug most commonly seen with a phenylpropionate ester (nandrolone phenylpropionate), although it is also used with testosterone in Sustanon and Omnadren.
Isocarpoate: Chemical Structure C6H12O2.
Also referred to as Isocaproic Acid; isohexanoate; 4-methylvaleric acid. Isocaproate begins to near enanthate in terms of release. The duration is still shorter, with a notable hormone level being sustained for approximately one week. This ester is used with testosterone in the blended products Sustanon and Omnadren.
Caproate: Chemical Structure C6H12O2.
Also referred to as Hexanoic acid; hexanoate; n-Caproic Acid; n-Hexoic acid; butylacetic acid; pentiformic acid; pentylformic acid; n-hexylic acid; 1-pentanecarboxylic acid; hexoic acid; 1-hexanoic acid; Hexylic acid; Caproic acid. This ester is identical to isocarpoate in terms of atom count and weight, but is laid out slightly different (Isocaproate has a split configuration, difficult to explain here but easy to see on paper). Release duration would be very similar to isocaproate (levels sustained for approximately one weak), perhaps coming slightly closer to enanthate due to its straight chain. Caproate is the slowest releasing ester used in Omnadren, which is why most athletes notice more water retention with this compound.
Enanthate: Chemical Structure C7H14O2.
Also referred to as heptanoic acid; enanthic acid; enanthylic acid; heptylic acid; heptoic acid; Oenanthylic acid; Oenanthic acid. Enanthate is one of the most prominent esters used in steroid manufacture (most commonly seen with testosterone but is also used in other compounds like Primobolan Depot). Enanthate will release a steady (yet fluctuating as all esters are) level of hormone for approximately 10-14 days. Although in medicine enanthate compounds are often injected on a bi-weekly or monthly basis, athletes will inject at least weekly to help maintain a uniform blood level.
Cypionate: Chemical Structure C8H14O2.
Also referred to as Cyclopentylpropionic acid, cyclopentylpropionate. Cypionate is a very popular ester here in the U.S., although it is scarcely found outside this region. Its release duration is almost identical to enanthate (10-14 days), and the two are likewise thought to be interchangeable in U.S. medicine. Althletes commonly hold the belief than cypionate is more powerful than enanthate, although realistically there is little difference between the two. The enanthate ester is in fact slightly smaller than cypionate, and it therefore releases a small (perhaps a few milligrams) amount of steroid more in comparison.
Decanoate: Chemical Structure C10H20O2.
Also referred to as decanoic acid; capric acid; caprinic acid; decylic acid, Nonanecarboxylic acid. The Decanoate ester is most commonly used with the hormone nandrolone (as in Deca-Durabolin) and is found in virtually all corners of the world. Testosterone decanoate is also the longest acting constituent in Sustanon, greatly extending its release duration. The release time with Decanoate compounds is listed to be as long as one month, although most recently we are finding that levels seem to drop significantly after two weeks. To keep blood levels more uniform, athletes (as they have always known to do) will follow a weekly injection schedule.
Undecylenate: Chemical Structure C11H20O2.
Also referred to as Undecylenic acid; Hendecenoic acid; Undecenoic acid. This ester is very similar to decanoate, containing only one carbon atom more. Its release duration is likewise very similar (approximately 2-3 weeks), perhaps extending a day or so past that seen with decanoate. Undecylenate seems to be exclusive to the veterinary preparation Equipoise (boldenone undecylenate), although there is no reason it would not work well in human-use preparations (Equipoise certainly works fine for athletes). Again, weekly injections are most common.
Undecanoate: Chemical Structure C11H22O2.
Also referred to as Undecanoic Acid; 1-Decanecarboxylic acid; Hendecanoic acid; Undecylic acid. Undecanoate is not a commonly found ester, and only appears to be used in the nandrolone preparation Dynabolan, and oral testosterone undecanoate (Andriol). Since this ester is chemically very similar to undecylenate (it is only 2 hydrogen atoms larger), it has a similar release duration (approximately 2-3 weeks). Although this ester is used in the oral preparation Andriol, there is no reason to believe it carries any properties unique of other esters. Andriol in fact works very poorly at delivering testosterone, bolstering the idea that oral administration is not the idea use of esterified androgens.
Laurate: Chemical structure C12H24O2.
Also referred to as Dodecanoic acid, laurostearic acid, duodecyclic acid, 1-undecanecarboxylic acid, and dodecoic acid. Laurate is the longest releasing ester used in commercial steroid production, although longer acting esters do exist. Its release duration would be closer to one month than the other esters listed above, although realistically we are probably to expect a notable drop in hormone level after the third week. Laurate is exclusively found in the veterinary nandrolone preparation Laurabolin, perhaps seen as slightly advantageous over a decanoate ester due to a less frequent injection schedule. Again athletes will most commonly inject this drug weekly, no doubt in part due to its low strength (25mg/ml or 50mg/ml).
STEROID ESTERS
by Roy Harper
It seems many people know very little about steroid esters. Many people believe it is the ester that determines the anabolic potential for any steroid. But in reality, there is absolutely no difference, in anabolic strength, from one ester to the other. Testosterone suspension is the same as Testosterone cypionate once the cypionate ester has been cleaved off by esterases in your body. Testosterone is testosterone no matter how you look at it. Now before you roll me up in a carpet and throw me over a bridge, I will admit that there is a large difference in how esters affect the release of the steroid. The key is time release (read half-life). Esters essentially delay the release of a steroid. Regardless of whether you injected 500mg of Testosterone suspension or 500mg of Testosterone cypionate, you will end up with approximately 500mg Testosterone in your system (ok, there is going to be slightly less testosterone with the cypionate because of the weight of the ester, but I’ll explain that later). The difference between the two is that all of the 500 mg of testosterone suspension would be available and metabolized within 24 hours, whereas after a week half of the testosterone in the cypionate would be released. Is that it? That's all what esters do? Of course not! In fact the real purpose for esters is to change the properties of the parent drug. As shown above the half-life, can be altered through the use of an ester.
Let's go through some of the details about esters. Steroid molecules are carbon based, as with any earthly organic molecule. The base of the molecule is formed with a chain of carbon molecules. At the 17th position, i.e. the 17th carbon atom, there is a hydroxyl group (OH) that is bonded there. This is where the fun comes in, when this base steroid is hydrolyzed (removing the OH group) an ester can be added here. With the addition of the ester the solubility in oil can be changed, the half-life can be changed, etc. To add to this, the more carbon atoms the ester has the more solubility in oil increases and the half life increases. Therefore, esters such as acetic acid (two carbons) and propionic acid (three carbons) aren't as soluble and have a quick half live. On the other hand, esters such as decanoic acid (ten carbons) and undecanoic acid (eleven carbons) are very soluble in oil and have longer half lives.
Well let's put esters on everything! How about those 17Alpha Alkylated steroids? You know the ones that are orally active. Well, as with esters, there is an extra chemical that is added at the 17th position. What's added is a 17-methyl group. This is what makes winstrol and dianabol great steroids. Without them the liver would metabolize these steroids instantaneously. A 17AA steroid ester without the 17-methyl group would be inactive. A 17AA steroid ester attached with the 17-methyl group would prevent the base steroid from being removed from the ester. Although I've heard rumors that 17AA esters have been made, I highly doubt it's even possible.
And now for the juicy part, how to make your esters at home. Note this is a theoretical discussion and not actual instructions. It would be very dangerous not only in the process of esterfication but also injecting the resulting product. With all that said, first we need to begin with a base steroid. The easiest would be using USP grade powder. Then you would add in one part of anhydrid of the ester you want, to two parts of pyridine. For example you would add in 500mg of cypionic anhydride to 250mg pyridine. Then the base steroid would react within this mixture at ten parts mixture to one part base steroid. Once the reaction has occurred you would then purify the mixture with twenty parts water and one part ether. Decant the water while adding it to another ten parts water. Once complete, simply recrystalize the steroid, and there you have it. A steroid ester made at home. But remember if you aren't a chemist you should not even think of doing this.
Well let’s look at the opposite side of the spectrum. Suppose you want to remove the ester from a steroid ester. Start by dissolving the steroid ester in water. If the ester is already in an oil solution then you better know what the oil is and look it up in the Merck index to figure out how to remove either the oil or steroid ester. Once dissolved in water the ester can be removed. As above you need to use the Merck index to figure it out for each ester. If you got this far then you have your very own base steroid.
You may be thinking to yourself "If this is so complicated, how come our bodies can do it so easily?" Well the answer my friend is invariably, enzymes. Ahh the power of enzymes. Is there anything they can't do? Well looking closer at how our bodies do it, we see that the enzyme esterase is responsible for this process. It follows the same procedure above, technically speaking, and requires water to break the steroid from the ester. But the more oil and the more soluble in oil the steroid ester becomes, the harder it is for esterase to perform its duty. The use of other enzymes to remove the steroid ester from the oil which will lengthen the amount time until the ester is removed. Hence the change in half-life for longer chained esters.
Remember the ester does not determine the anabolic properties of a steroid. With this in mind, please recall that you should consider the timing of injections and the purpose for the steroid. For example Testosterone propionate could be used for a very short cycle. While Nandrolone decanoate would be used in a longer cycle. If you want to determine the half-life of a steroid ester use the following guide:
Ester
Number of Carbon Atoms
Formate
1
Acetate
2
Propionate
3
Butyrate
4
Valerate
5
Hexanoate
6
Heptanoate
7
Enanthate
7
Octanoate
8
Cypionate
8
Nonanoate
9
Decanoate
10
Undecanoate
11
If the ester you're looking is not here, simply look on the Internet to find how many carbon atoms there are in the ester. Approximately each carbon atoms is equal to a half-life of 1.5 days. Therefore a decanoate steroid ester would have a half-life of 15 days (11 carbon atoms * 1.5 days constant). In case you're wondering what the half-life is, it's the amount of time before half of the original substance is used. For instance 15 days after an injection of 200mg of deca, 100mg would be left.
Now, you have to remember that the ester is going to add more weight to the molecule. The larger the ester the less base steroid there is going to be in a 100mg steroid ester. You can use the following chart to figure this out:
Chemical
Formula
Molecular Weight
Mg of Testosterone
Testosterone (no ester)
C19 H28 O2
288.4
100mg
Acetate
C2 H2 O
42.1
87.26mg
Propionate
C3 H4 O
56.1mg
83.72mg
Enanthate*
C7 H12 O
112.2mg
71.99mg
Cypionate
C8 H4 O
124.2mg
69.90mg
Decanoate
C10 H18 O
154.3mg
65.15mg
Undecanoate info not availible
*Data Extrapolated from another formula (may not be exact)
Hopefully all of this has educated you in the wonderful world of esters. Never again will you wonder about the difference between acetate and undecanoate.
How do esters differ in structure?
While quite an array of names exist and make the issue seem complicated, the main difference between different esters is simply the number of carbon atoms in the ester. Propionate, as shown above, has three carbons, whereas acetate has two, isobutyrate has four, enanthate has seven, cypionate has eight, and decanoate has ten. On occasion there are more unusual esters, such as cyclohexylmethylcarbonate (used in Parabolan) which has eight carbons and one more oxygen than the above esters do.
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How do esters change the physical properties of steroids?
Testosterone, nandrolone, and other anabolic steroids have poor solubility in either water or oil. Esterifying them improves oil solubility. This enables useful dosages of perhaps 100 mg or more per cc. But the more carbons the ester has, the lower the water solubility becomes, and the higher the partition coefficient (ratio between lipid and water solubilities) becomes. If the partition coefficient is high, then at any moment a high proportion of the prodrug is dissolved in oil or body fat, and only a small proportion is dissolved in water.
This is important. If testosterone itself is given in oil solution, it transfers too easily from oil to the water in the blood. The result is that an oil injection of testosterone gives a sudden spike in testosterone levels, which rapidly drops. Injections would be required at least twice per day, and perhaps even more often. Improving the oil solubility and decreasing the water solubility slows this transfer, and extends the half-life of the drug to several days or more.
The number of carbons also has a small effect in that it reduces the parent drug’s proportion of the total weight. E.g., it would take 344 mg of testosterone propionate, or 401 mg of testosterone enanthate to give the same amount of testosterone as in 288 mg of testosterone suspension.
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How are esters converted back to the parent drug?
The ester bond is fairly easily broken under the right conditions. If the molecule is dissolved in water, this can occur by a simple chemical reaction, yielding the parent drug and a carboxylic acid. For example, if the steroid used is testosterone propionate, testosterone and propionic acid are released. Carboxylic acids are safe and natural in the body in reasonable amounts. It should not be thought that these are strong acids because they are not: they are acids in the same sense that, e.g., Vitamin C or lactic acid are acids. Furthermore, the amount of carboxylic acid present at any time is extremely low.
The carboxylic acids do not have any activities of interest. Once the ester group is removed, it has done its job, and the parent drug acts in its normal manner.
Besides the simple chemical hydrolysis described above, the esters can be removed by enzymes in the blood called esterases, though water still is required for the reaction. The great majority of hydrolysis occurs with the help of these enzymes or by non-specific reactions with proteins. These reaction cannot take place while the esterified steroid is dissolved in fat. Thus, while the esterified steroids are dissolved in fat, they are protected from hydrolyis, and thus serve as a depot for the drug, giving extended duration of action.
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What is the significance of the partition coefficient?
Differences in partition coefficient seem to account almost fully for the differences between various esters of anabolic steroids, as shown by Chaudry and James.1,2 To understand their work, though, it is necessary first to consider the methods they used to obtain their data on the anabolic and androgenic effects of the drugs tested.
These scientists are not using those terms in the manner which many bodybuilding authors do. The anabolic effect is measured by increase in weight of the levator ani muscle in the rat, and the androgenic effect is measured by increase in weight of the seminal vesicles and prostate. These measurements are neither perfectly indicative of muscle-building value to bodybuilders nor to any particular undesired side effect except perhaps prostate enlargement. Despite the limitations of the method, this was the assay method available.
A number of esters of nandrolone were studied, using various single doses, but only the results from a single dose of 1 mg are given here. The results are as follows:
Parent Drug
Ester
# of Carbons
Anabolic Effect
Anabolic / Androgenic Ratio
PRC** (P) x10-3
Nandrolone
formate
1
1176
13:1
15*
acetate
2
1594
11:1
25*
propionate
3
1880
10:1
41*
butyrate
4
1488
7:1
69
valerate
5
2526
9:1
115*
hexanoate
6
3731
9:1
192
heptanoate
7
6559
13:1
269
octanoate
8
5557
15:1
611
nonanoate
9
5080
19:1
455
decanoate
10
7735
25:1
802
undecanoate
11
6576
32:1
1460
*extrapolated from P of the butyrate ester
** partition ratio coefficient
The anabolic effect was found to be predictable according to the equation:
log (anabolic effect) = 7.33 log P – 0.636 log P2 –17.8
The accuracy of predictions was quite high (r = 0.970) and the F value, indicating the statistical significance of the equation, was very high at 61. Thus, the observed anabolic effect of these ester prodrugs of nandrolone was found to be highly correlated with partition coefficient.
Higher partition coefficients were also strongly correlated with higher anabolic/androgenic ratio.
It was also found that the times of first and second peaks of drug level after injection were predictable from P with good accuracy and high significance.
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How can the greatly higher anabolic effects of the long chain esters be explained?
While the authors do not make note of it in either article cited, there is a simple explanation for the observed result. Long chain esters of anabolic steroids are not many more times potent than short chain, if indeed they are any more potent at all. Yet in the above study, the undecanoate ester was found to give 3.5 times the effect of the propionate ester. Why?
There is a difference in pharmacokinetics (the time course of the drug in the body). Although the same 1 mg dose is being given in each case, it is either present in the serum of the animal at a relatively high concentration for a relatively short time for the shorter chain esters, or at lower concentration for a longer time for the longer chain esters. This difference can be quite large: the undecanoate ester can be predicted to have a half-life 36 times longer than that of the propionate ester.3
With most drugs, response is not proportional to the dose, but to the log of the dose. Assuming that the dose is well into the effective range, taking ¼ the dose does not result in only ¼ the result, but in ½ the result.
Viewed in this light, if the nandrolone propionate had been given in 36 divided doses over the same length of time that nandrolone undecanoate was in the system, in a manner to match its pharmacokinetics, one would expect 1/6 the result from each individual dose before accounting for molecular weight differences. The cumulative response would be 36 times 1/6, or six times the observed result from the single large dose. If we then correct for the lower molecular weight of the propionate ester, which delivers more nandrolone per mg. than does the undecanoate ester, we would predict 3.3 times more response than from the single large dose. In fact the observed response of the undecanoate ester was 3.5 times that of the propionate ester. This difference is within experimental error.
This calculation I have performed is also supported by experimental evidence performed by van der Vies4. His research showed that when the dose of nandrolone was divided into frequent small injections in such a pattern as to mimic the pharmacokinetics of esters, the anabolic effect became identical to that of the esters.
Thus, pharmacokinetics, the log dose/response curve, and differences in molecular weight are sufficient to account for observed differences in anabolic effect between different esters of an anabolic steroid, or between an ester and the parent drug.
This correlates with my observation that anabolic effect of testosterone esters is equal, so long as each is administered reasonably frequently: at least once per half-life, and preferably twice. E.g., if testosterone propionate yielding some given amount of testosterone per week is administered daily, or at least every other day, it will give results comparable to testosterone cypionate administered at least once every week, and preferably twice per week, that yields the same amount of testosterone per week.
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How can the differences in anabolic/androgenic ratio be accounted for, and how significant are they?
Partition coefficient is key information for determining how a drug will be distributed in the body. The ratio of solubility between oil and water gives good relative predictions of the ratios of solubility between blood and target organs. Different target organs, for example the levator ani muscle vs. the prostate, may have different solubility properties. A more lipophilic drug (one with a high partition coefficient) would distribute much moreso into a more lipophilic target organ than into a less lipophilic one. It may then be the case that the longer chain esters partition more preferentially into muscle and less preferentially into the skin and prostate, but this is not demonstrated.
For this to be the case, it would be necessary for the esterified steroids to be distributed throughout the body after slow release from the oil depot injection site, rather than to have only free parent drug released from the injection site. This is an agreement with the findings of James et al.3 which demonstrate that the esters do indeed become distributed throughout the body after injection.
I don’t, however, expect that differences in distribution are the primary reason for observed differences in anabolic/androgenic ratio between different steroid esters. There is another possible explanation for differences in this ratio. In the same work referenced above concerning anabolic effect as a function of pharmacokinetics, van der Vies showed that if nandrolone is administrated with frequent dosage patterns designed to give the same trend of serum levels as seen with either phenylpropionate or decanoate, nandrolone itself gave the same anabolic/androgenic ratios as each of these esters of nandrolone.
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What application does this information on anabolic/androgenic ratio have to female bodybuilding?
Since keeping androgen levels constant and moderate gives a higher anabolic/androgenic ratio than using the same total amount of drug per week but allowing levels to spike and then subside, female bodybuilders are better advised to use either long acting esters, or if short acting esters are used, to inject small doses frequently (twice per half-life). And for the same reason, a given amount of oral steroids per day is better taken in divided doses than in a single larger dose.
This is probably because tissues with sex-specific traits exhibit thresholds to effect of androgens. Below the threshold, nothing happens, but above it, cellular differentiation occurs. Thus, while female levels of androgens are about 10% that of a male's, 10 years of female levels of androgen will not grow as much beard or change the voice as much as one month of male levels. The threshold simply is not crossed at the lower levels, but is crossed at the higher levels.
Female bodybuilders will do better to avoid spikes in androgen level that cross this threshold. Therefore, consistent low doses are better than spiking with intermittent high doses, and advice to use 100 mg/week of testosterone propionate to avoid virilization simply makes no sense (and in practice, often fails.)
It should still be noted that some women will suffer virilization with almost any dose of anabolic steroid, regardless of dosing pattern.
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What are the half-lives of different esters?
Shorter chain esters have shorter half-lives, because of their lower partition coefficient. Testosterone cypionate has a half-life of 8 days5, the enanthate ester has a half-life of 4 days6, and nandrolone decanoate has a half-life of 8 days7. These figures are only approximate. The difference between these values for cypionate and enanthate probably includes difference attributable to different measuring techniques. The actual difference is probably not more than two days.
In the rat, where half-lives of anabolic steroid esters are similar to those in humans but somewhat shorter, the half-lives of the phenylpropionate, decanoate, and laurate esters are 1, 5, and 10 days respectively.3 The same trend would be expected in man.
Half-life is linearly related to log partition coefficient, which is itself linearly related to the carbon chain length, the exception being if the ester is an unusual one such as phenylpropionate. This was shown by James et al.3 for the formate through valerate esters of testosterone in the rat. The half-life of testosterone propionate was approximately 4 days, and each carbon added to or subtracted from that chain length changed half-life by about 1.5 days.
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How are steroid esters made, and can esters be made of prohormones?
The most convenient method of synthesis of steroid esters is reaction of the steroid in a 2:1 mixture of pyridine and the anhydride of the desired ester: for example, propionic anhydride would be used to make the propionate ester. A large excess (at least 10 times) of the anhydride compared to the steroid would be required. This would then be purified by diluting with at least 10 parts of water to each part of pyridine, adding 1 part ether, decanting the water after shaking, and then washing with 10 parts water repeatedly in a separatory funnel. This would be followed preferably by recrystallization or chromatography for purification.
Esters cannot be made of dione prohormones because they do not have an –OH group. Esters can be made of the diols, but purification by recrystallization probably is not possible because the product would be a mixture of 3a and 3b esters, which could be expected to yield an oily mess, or perhaps an amorphous solid. Further difficulties would include the fact that for the diols, the starting material from at least some manufacturers is of considerably less than 100% purity. I personally would not even consider injecting the product of the above reaction without some further purification besides the water wash. An even more serious consideration is that by esterifying the prohormone, one is arguably manufacturing a controlled substance. To say the least, this is a real no-no with the Drug Enforcement Agency, even moreso than possession or importing, both of which are already quite serious crimes. Therefore I cannot recommend manufacturing esters of diol prohormones, but for the sake of completeness in an article on steroid esters, I thought I would mention how they can be made and what the difficulties are.
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Can we make esters of Winstrol, Dianabol, etc., for injection?
While there are a number of interesting oral steroids that, at first glance, would be appealing candidates for making esters, in fact there are very good reasons why no such products are available. Indeed, there are absolutely no 17-alkylated steroid esters on the market.
First, they would be difficult to synthesize. The 17-methyl group which works to block liver enzymes from reacting with the steroid molecule will also hinder the material one would use to make the ester from reacting with the steroid.
More seriously, there is the fact that a 17-methyl would also block enzymes in the body from hydrolyzing (removing) the ester, which would be necessary to yield the active steroid.
So I do not expect that you will ever see esters of Winstrol, Dianabol, or any 17-alkylated steroid on the market, and don’t recommend that anyone try making them. They would probably be inactive, or if they have any activity, it would be very low.
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Summary, and Practical Implications
Shorter chain esters must be injected more frequently than longer chain esters if consistent blood levels are desired. Consistent blood levels probably lead to the greatest efficiency of use for the drug and the highest anabolic/androgenic ratio. The activity of long chain esters can be mimicked by frequent administration of short chain esters.
While it has been alleged popularly that some esters aromatize more than others, there is no support for this in the scientific literature, and the concept makes relatively little sense since the ester itself is very far removed from the site of reaction of aromatization. The claims in this area seem flawed: for example, in World Anabolic Review 1996, the text makes plain that the comparison being made is between a weekly dose of 350 mg of testosterone propionate vs. a weekly dose of over a gram of testosterone enanthate or other long chain esters. While it is surely true that, as they say, side effects of the latter will be more pronounced than those of the former, it is unreasonable to attribute this difference to the ester used.
All testosterone drugs aromatize, and if estrogenic effects are not desired, then anti-estrogenic agents should be used for any of the esters and in the same manner, regardless of the ester used.
While the theory of the effects of esterification of steroids is interesting and somewhat complicated, the practical implications are simple. Differences between parent drugs are far more important than differences between esters of the same drug. And if the ester is different, the key difference to the bodybuilder is in half-life of the drug. Longer half-lives add convenience, and shorter-half lives allow the drug to exit the body more quickly. Short half-life also can allow fairly rapid drug clearance to occur before drug testing. Testosterone propionate is therefore a drug of choice for the tested athlete. And if a brief alternating cycle plan is being used, a short half-life allows high dosing during the "on" weeks with rapid clearance to non-inhibiting levels during the off weeks. Besides these things, however, there are no significant differences between drugs resulting from use of different esters.
(A shorter version of this article previously appeared in Peak Training Journal. New information has been added for MESO/Rx.)
References:
1. Chaudry, M.A.Q.; James, K.C.; et al. J. Pharm. Pharmac., 1976, 28, 882-885
2. Chaudry, M.A.Q.; James, K.C. J. Med. Chem., 1974, 17, 157-161
3. James, K.C.; Nicholls, P.J.; Roberts M. J. Pharm. Pharmac., 1969, 21, 24-27
4. van der Vies, J. Acta Endocrinologica., 1985, 271, 38-44
5. United States Pharmacopeial Convention, USP DI: Drug Information for the Health Care Professional, 1993, 108. Rand McNally, Taunton Mass.
6. Weinbauer, G.F.; Jackwerth, B; et al. Acta Endocrinol. Copenh., 1990, 122, 432-42
7. Belkien, L.; Schurmeyer, T.; et al. J. Steroid Biochem., 1985, 22, 623-629
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Hier de originele thread.
Testosterone Ester Report
One of the most misunderstood subjects in the world of steroids is the ester--the mechanism by which injectable esterified steroids like testosterone cypionate, testosterone enanthate, and Sustanon work. If you take a quick look around the Internet you will probably find countless articles that consider one form of a steroid far more effective than another. Arguments over the superiority of cypionate to enanthate, or Sustanon to all other testosterones are of course very common. Such arguments are in all practicality, baseless. In this report we'll take an authoritative look at the ester and what specifically it does to a steroid.
WHAT AN ESTER IS, AND HOW IT WORKS
I'm sure that if you have taken an interest in anabolic steroids you have noticed the similarities on the labeling of many drugs. Let's look at testosterone for example. One can find compounds like testosterone cypionate, enanthate, propionate, heptylate; caproate, phenylpropionate, isocaproate, decanoate, acetate, the list goes on and on. In all such cases the parent hormone is testosterone, which had been modified by adding an ester (enanthate, propionate etc.) to its structure. The following question arises: What is the difference between the various esterified versions of testosterone in regards to their use in bodybuilding?
An ester is a chain composed primarily of carbon and hydrogen atoms. This chain is typically attached to the parent steroid hormone at the 17th carbon position (beta orientation), although some compounds do carry esters at position 3 (for the purposes of this article it is not crucial to understand the exact position of the ester). Esterification of an injectable anabolic/androgenic steroid basically accomplishes one thing, it slows the release of the parent steroid from the site of injection. This happens because the ester will notably lower the water solubility of the steroid, and increase its lipid (fat) solubility. This will cause the drug to form a deposit in the muscle tissue, from which it will slowly enter into circulation as it is picked up in small quantities by the blood. Generally, the longer the ester chain, the lower the water solubility of the compound, and the longer it will take to for the full dosage to reach general circulation.
Slowing the release of the parent steroid is a great benefit in steroid medicine, as free testosterone (or other steroid hormones) previously would remain active in the body for a very short period of time (typically hours). This would necessitate an unpleasant daily injection schedule if one wished to maintain a continuous elevation of testosterone (the goal of testosterone replacement therapy). By adding an ester, the patient can visit the doctor as infrequently as once per month for his injection, instead of having to constantly re-administer the drug to achieve a therapeutic effect. Clearly without the use of an ester, therapy with an injectable anabolic/androgen would be much more difficult.
Esterification temporarily deactivates the steroid molecule. With a chain blocking the 17th beta position, binding to the androgen receptor is not possible (it can exert no activity in the body). In order for the compound to become active the ester must therefore first be removed. This automatically occurs once the compound has filtered into blood circulation, where esterase enzymes quickly cleave off (hydrolyze) the ester chain. This will restore the necessary hydroxyl (OH) group at the 17th beta position, enabling the drug to attach to the appropriate receptor. Now and only now will the steroid be able to have an effect on skeletal muscle tissue. You can start to see why considering testosterone cypionate much more potent than enanthate makes little sense, as your muscles are seeing only free testosterone no matter what ester was used to deploy it.
ACTIONS OF DIFFERENT ESTERS
There are many different esters that are used with anabolic/androgenic steroids, but again, they all do basically the same thing. Esters vary only in their ability to reduce a steroid's water solubility. An ester like propionate for example will slow the release of a steroid for a few days, while the duration will be weeks with a decanoate ester. Esters have no effect on the tendency for the parent steroid to convert to estrogen or DHT (dihydrotestosterone: a more potent metabolite) nor will it effect the overall muscle-building potency of the compound. Any differences in results and side effects that may be noted by bodybuilders who have used various esterified versions of the same base steroid are just issues of timing. Testosterone enanthate causes estrogen related problems more readily than Sustanon, simply because with enanthate testosterone levels will peak and trough much sooner (1-2 week release duration as opposed to 3 or 4). Likewise testosterone suspension is the worst in regards to gyno and water bloat because blood hormone levels peak so quickly with this drug. Instead of waiting weeks for testosterone levels to rise to their highest point, here we are at most looking at a couple of days. Given an equal blood level of testosterone, there would be no difference in the rate of aromatization or DHT conversion between different esters. There is simply no mechanism for this to be possible.
There is however one way that we can say an ester does technically effect potency; it is calculated in the steroid weight. The heavier the ester chain, the greater is its percentage of the total weight. In the case of testosterone enanthate for example, 250mg of esterified steroid (testosterone enanthate) is equal to only 180mg of free testosterone. 70mgs out of each 250mg injection is the weight of the ester. If we wanted to be really picky, we could consider enanthate slightly MORE potent than cypionate (I know this goes against popular thinking) as its ester chain contains one less carbon atom (therefore taking up a slightly smaller percentage of total weight). Propionate would of course come out on top of the three, releasing a measurable (but not significant) amount more testosterone per injection than cypionate or enanthate.
IN CONCLUSION
While the advent of esters certainly constitutes an invaluable advance in the field of anabolic steroid medicine, clearly you can see that there is no magic involved here. Esters work in a well-understood and predictable manner, and do not alter the activity of the parent steroid in any way other than to delay its release. Although the lure surrounding various steroid products like testosterone cypionate, Sustanon, Omnadren etc. certainly makes for interesting conversation, realistically it just amounts to misinformation that the athlete would be better off ignoring. Testosterone is testosterone and anyone who is going to tell you one ester form of this (or any) hormone is much better than another one should do a little more research, and a lot less talking.
ESTER PROFILES
Sustanon: The "king" of testosterone blends.
The four different testosterone esters in this product certainly look appealing to the consumer, there is no denying that. But for the athlete I think it is all just a matter of marketing (Hell, why buy one ester when you can get four?). In clinical situations I can see some strong uses for it. If you were undergoing testosterone replacement therapy for example, you would probably find Sustanon a much more comfortable option than testosterone enanthate. You would need to visit the doctor less frequently for an injection, and blood levels should be more steadily maintained between treatments. But for the bodybuilder who is injecting 4 ampules of Sustanon per week, there is no advantage over other testosterone products. In fact, the high price tag for Sustanon usually makes it a very poor buy in the face of cheaper testosterone enanthate/cypionate. Bodybuilders should probably stop looking at the four ester issue, and stick with totals (Sustanon is just a 250mg testosterone ampule). Were enanthate to be available for say $10 per amp of 250mg, and Sustanon priced nearly double that, buying the Sustanon would be like throwing money away. If you could get nearly double the milligram amount for the same price with enanthate, this is the better product to go with hands down. Leave the high priced stuff for the guys who don't know any better.
Acetate: Chemical Structure C2H4O2.
Also referred to as Acetic Acid; Ethylic acid; Vinegar acid; vinegar; Methanecarboxylic acid. Acetate esters delay the release of a steroid for only a couple of days. Contrary to what you may have read, acetate esters do not increase the tendency for fat removal. Again, there is no known mechanism for it to do so. This ester is used on oral primobolan tablets (metenolone acetate), Finaplix (trenbolone acetate) implant pellets, and occasionally testosterone.
Propionate: Chemical Structure C3H6O2.
Also referred to as Carboxyethane; hydroacrylic acid; Methylacetic acid; Ethylformic acid; Ethanecarboxylic acid; metacetonic acid; pseudoacetic acid; Propionic Acid. Propionate esters will slow the release of a steroid for several days. To keep blood levels from fluctuating greatly, propionate compounds are usually injected two to three times weekly. Testosterone propionate and methandriol dipropionate (two separate propionate esters attached to the parent steroid methandriol) are popular items.
Phenylpropionate: Chemical Structure C9H10O2.
Also referred to as Propionic Acid Phenyl Ester. Phenylpropionate will extend the release of active steroid a few days longer than propionate. To keep blood levels even, injections are given at least twice weekly. Durabolin is the drug most commonly seen with a phenylpropionate ester (nandrolone phenylpropionate), although it is also used with testosterone in Sustanon and Omnadren.
Isocarpoate: Chemical Structure C6H12O2.
Also referred to as Isocaproic Acid; isohexanoate; 4-methylvaleric acid. Isocaproate begins to near enanthate in terms of release. The duration is still shorter, with a notable hormone level being sustained for approximately one week. This ester is used with testosterone in the blended products Sustanon and Omnadren.
Caproate: Chemical Structure C6H12O2.
Also referred to as Hexanoic acid; hexanoate; n-Caproic Acid; n-Hexoic acid; butylacetic acid; pentiformic acid; pentylformic acid; n-hexylic acid; 1-pentanecarboxylic acid; hexoic acid; 1-hexanoic acid; Hexylic acid; Caproic acid. This ester is identical to isocarpoate in terms of atom count and weight, but is laid out slightly different (Isocaproate has a split configuration, difficult to explain here but easy to see on paper). Release duration would be very similar to isocaproate (levels sustained for approximately one weak), perhaps coming slightly closer to enanthate due to its straight chain. Caproate is the slowest releasing ester used in Omnadren, which is why most athletes notice more water retention with this compound.
Enanthate: Chemical Structure C7H14O2.
Also referred to as heptanoic acid; enanthic acid; enanthylic acid; heptylic acid; heptoic acid; Oenanthylic acid; Oenanthic acid. Enanthate is one of the most prominent esters used in steroid manufacture (most commonly seen with testosterone but is also used in other compounds like Primobolan Depot). Enanthate will release a steady (yet fluctuating as all esters are) level of hormone for approximately 10-14 days. Although in medicine enanthate compounds are often injected on a bi-weekly or monthly basis, athletes will inject at least weekly to help maintain a uniform blood level.
Cypionate: Chemical Structure C8H14O2.
Also referred to as Cyclopentylpropionic acid, cyclopentylpropionate. Cypionate is a very popular ester here in the U.S., although it is scarcely found outside this region. Its release duration is almost identical to enanthate (10-14 days), and the two are likewise thought to be interchangeable in U.S. medicine. Althletes commonly hold the belief than cypionate is more powerful than enanthate, although realistically there is little difference between the two. The enanthate ester is in fact slightly smaller than cypionate, and it therefore releases a small (perhaps a few milligrams) amount of steroid more in comparison.
Decanoate: Chemical Structure C10H20O2.
Also referred to as decanoic acid; capric acid; caprinic acid; decylic acid, Nonanecarboxylic acid. The Decanoate ester is most commonly used with the hormone nandrolone (as in Deca-Durabolin) and is found in virtually all corners of the world. Testosterone decanoate is also the longest acting constituent in Sustanon, greatly extending its release duration. The release time with Decanoate compounds is listed to be as long as one month, although most recently we are finding that levels seem to drop significantly after two weeks. To keep blood levels more uniform, athletes (as they have always known to do) will follow a weekly injection schedule.
Undecylenate: Chemical Structure C11H20O2.
Also referred to as Undecylenic acid; Hendecenoic acid; Undecenoic acid. This ester is very similar to decanoate, containing only one carbon atom more. Its release duration is likewise very similar (approximately 2-3 weeks), perhaps extending a day or so past that seen with decanoate. Undecylenate seems to be exclusive to the veterinary preparation Equipoise (boldenone undecylenate), although there is no reason it would not work well in human-use preparations (Equipoise certainly works fine for athletes). Again, weekly injections are most common.
Undecanoate: Chemical Structure C11H22O2.
Also referred to as Undecanoic Acid; 1-Decanecarboxylic acid; Hendecanoic acid; Undecylic acid. Undecanoate is not a commonly found ester, and only appears to be used in the nandrolone preparation Dynabolan, and oral testosterone undecanoate (Andriol). Since this ester is chemically very similar to undecylenate (it is only 2 hydrogen atoms larger), it has a similar release duration (approximately 2-3 weeks). Although this ester is used in the oral preparation Andriol, there is no reason to believe it carries any properties unique of other esters. Andriol in fact works very poorly at delivering testosterone, bolstering the idea that oral administration is not the idea use of esterified androgens.
Laurate: Chemical structure C12H24O2.
Also referred to as Dodecanoic acid, laurostearic acid, duodecyclic acid, 1-undecanecarboxylic acid, and dodecoic acid. Laurate is the longest releasing ester used in commercial steroid production, although longer acting esters do exist. Its release duration would be closer to one month than the other esters listed above, although realistically we are probably to expect a notable drop in hormone level after the third week. Laurate is exclusively found in the veterinary nandrolone preparation Laurabolin, perhaps seen as slightly advantageous over a decanoate ester due to a less frequent injection schedule. Again athletes will most commonly inject this drug weekly, no doubt in part due to its low strength (25mg/ml or 50mg/ml).
STEROID ESTERS
by Roy Harper
It seems many people know very little about steroid esters. Many people believe it is the ester that determines the anabolic potential for any steroid. But in reality, there is absolutely no difference, in anabolic strength, from one ester to the other. Testosterone suspension is the same as Testosterone cypionate once the cypionate ester has been cleaved off by esterases in your body. Testosterone is testosterone no matter how you look at it. Now before you roll me up in a carpet and throw me over a bridge, I will admit that there is a large difference in how esters affect the release of the steroid. The key is time release (read half-life). Esters essentially delay the release of a steroid. Regardless of whether you injected 500mg of Testosterone suspension or 500mg of Testosterone cypionate, you will end up with approximately 500mg Testosterone in your system (ok, there is going to be slightly less testosterone with the cypionate because of the weight of the ester, but I’ll explain that later). The difference between the two is that all of the 500 mg of testosterone suspension would be available and metabolized within 24 hours, whereas after a week half of the testosterone in the cypionate would be released. Is that it? That's all what esters do? Of course not! In fact the real purpose for esters is to change the properties of the parent drug. As shown above the half-life, can be altered through the use of an ester.
Let's go through some of the details about esters. Steroid molecules are carbon based, as with any earthly organic molecule. The base of the molecule is formed with a chain of carbon molecules. At the 17th position, i.e. the 17th carbon atom, there is a hydroxyl group (OH) that is bonded there. This is where the fun comes in, when this base steroid is hydrolyzed (removing the OH group) an ester can be added here. With the addition of the ester the solubility in oil can be changed, the half-life can be changed, etc. To add to this, the more carbon atoms the ester has the more solubility in oil increases and the half life increases. Therefore, esters such as acetic acid (two carbons) and propionic acid (three carbons) aren't as soluble and have a quick half live. On the other hand, esters such as decanoic acid (ten carbons) and undecanoic acid (eleven carbons) are very soluble in oil and have longer half lives.
Well let's put esters on everything! How about those 17Alpha Alkylated steroids? You know the ones that are orally active. Well, as with esters, there is an extra chemical that is added at the 17th position. What's added is a 17-methyl group. This is what makes winstrol and dianabol great steroids. Without them the liver would metabolize these steroids instantaneously. A 17AA steroid ester without the 17-methyl group would be inactive. A 17AA steroid ester attached with the 17-methyl group would prevent the base steroid from being removed from the ester. Although I've heard rumors that 17AA esters have been made, I highly doubt it's even possible.
And now for the juicy part, how to make your esters at home. Note this is a theoretical discussion and not actual instructions. It would be very dangerous not only in the process of esterfication but also injecting the resulting product. With all that said, first we need to begin with a base steroid. The easiest would be using USP grade powder. Then you would add in one part of anhydrid of the ester you want, to two parts of pyridine. For example you would add in 500mg of cypionic anhydride to 250mg pyridine. Then the base steroid would react within this mixture at ten parts mixture to one part base steroid. Once the reaction has occurred you would then purify the mixture with twenty parts water and one part ether. Decant the water while adding it to another ten parts water. Once complete, simply recrystalize the steroid, and there you have it. A steroid ester made at home. But remember if you aren't a chemist you should not even think of doing this.
Well let’s look at the opposite side of the spectrum. Suppose you want to remove the ester from a steroid ester. Start by dissolving the steroid ester in water. If the ester is already in an oil solution then you better know what the oil is and look it up in the Merck index to figure out how to remove either the oil or steroid ester. Once dissolved in water the ester can be removed. As above you need to use the Merck index to figure it out for each ester. If you got this far then you have your very own base steroid.
You may be thinking to yourself "If this is so complicated, how come our bodies can do it so easily?" Well the answer my friend is invariably, enzymes. Ahh the power of enzymes. Is there anything they can't do? Well looking closer at how our bodies do it, we see that the enzyme esterase is responsible for this process. It follows the same procedure above, technically speaking, and requires water to break the steroid from the ester. But the more oil and the more soluble in oil the steroid ester becomes, the harder it is for esterase to perform its duty. The use of other enzymes to remove the steroid ester from the oil which will lengthen the amount time until the ester is removed. Hence the change in half-life for longer chained esters.
Remember the ester does not determine the anabolic properties of a steroid. With this in mind, please recall that you should consider the timing of injections and the purpose for the steroid. For example Testosterone propionate could be used for a very short cycle. While Nandrolone decanoate would be used in a longer cycle. If you want to determine the half-life of a steroid ester use the following guide:
Ester
Number of Carbon Atoms
Formate
1
Acetate
2
Propionate
3
Butyrate
4
Valerate
5
Hexanoate
6
Heptanoate
7
Enanthate
7
Octanoate
8
Cypionate
8
Nonanoate
9
Decanoate
10
Undecanoate
11
If the ester you're looking is not here, simply look on the Internet to find how many carbon atoms there are in the ester. Approximately each carbon atoms is equal to a half-life of 1.5 days. Therefore a decanoate steroid ester would have a half-life of 15 days (11 carbon atoms * 1.5 days constant). In case you're wondering what the half-life is, it's the amount of time before half of the original substance is used. For instance 15 days after an injection of 200mg of deca, 100mg would be left.
Now, you have to remember that the ester is going to add more weight to the molecule. The larger the ester the less base steroid there is going to be in a 100mg steroid ester. You can use the following chart to figure this out:
Chemical
Formula
Molecular Weight
Mg of Testosterone
Testosterone (no ester)
C19 H28 O2
288.4
100mg
Acetate
C2 H2 O
42.1
87.26mg
Propionate
C3 H4 O
56.1mg
83.72mg
Enanthate*
C7 H12 O
112.2mg
71.99mg
Cypionate
C8 H4 O
124.2mg
69.90mg
Decanoate
C10 H18 O
154.3mg
65.15mg
Undecanoate info not availible
*Data Extrapolated from another formula (may not be exact)
Hopefully all of this has educated you in the wonderful world of esters. Never again will you wonder about the difference between acetate and undecanoate.
How do esters differ in structure?
While quite an array of names exist and make the issue seem complicated, the main difference between different esters is simply the number of carbon atoms in the ester. Propionate, as shown above, has three carbons, whereas acetate has two, isobutyrate has four, enanthate has seven, cypionate has eight, and decanoate has ten. On occasion there are more unusual esters, such as cyclohexylmethylcarbonate (used in Parabolan) which has eight carbons and one more oxygen than the above esters do.
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How do esters change the physical properties of steroids?
Testosterone, nandrolone, and other anabolic steroids have poor solubility in either water or oil. Esterifying them improves oil solubility. This enables useful dosages of perhaps 100 mg or more per cc. But the more carbons the ester has, the lower the water solubility becomes, and the higher the partition coefficient (ratio between lipid and water solubilities) becomes. If the partition coefficient is high, then at any moment a high proportion of the prodrug is dissolved in oil or body fat, and only a small proportion is dissolved in water.
This is important. If testosterone itself is given in oil solution, it transfers too easily from oil to the water in the blood. The result is that an oil injection of testosterone gives a sudden spike in testosterone levels, which rapidly drops. Injections would be required at least twice per day, and perhaps even more often. Improving the oil solubility and decreasing the water solubility slows this transfer, and extends the half-life of the drug to several days or more.
The number of carbons also has a small effect in that it reduces the parent drug’s proportion of the total weight. E.g., it would take 344 mg of testosterone propionate, or 401 mg of testosterone enanthate to give the same amount of testosterone as in 288 mg of testosterone suspension.
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How are esters converted back to the parent drug?
The ester bond is fairly easily broken under the right conditions. If the molecule is dissolved in water, this can occur by a simple chemical reaction, yielding the parent drug and a carboxylic acid. For example, if the steroid used is testosterone propionate, testosterone and propionic acid are released. Carboxylic acids are safe and natural in the body in reasonable amounts. It should not be thought that these are strong acids because they are not: they are acids in the same sense that, e.g., Vitamin C or lactic acid are acids. Furthermore, the amount of carboxylic acid present at any time is extremely low.
The carboxylic acids do not have any activities of interest. Once the ester group is removed, it has done its job, and the parent drug acts in its normal manner.
Besides the simple chemical hydrolysis described above, the esters can be removed by enzymes in the blood called esterases, though water still is required for the reaction. The great majority of hydrolysis occurs with the help of these enzymes or by non-specific reactions with proteins. These reaction cannot take place while the esterified steroid is dissolved in fat. Thus, while the esterified steroids are dissolved in fat, they are protected from hydrolyis, and thus serve as a depot for the drug, giving extended duration of action.
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What is the significance of the partition coefficient?
Differences in partition coefficient seem to account almost fully for the differences between various esters of anabolic steroids, as shown by Chaudry and James.1,2 To understand their work, though, it is necessary first to consider the methods they used to obtain their data on the anabolic and androgenic effects of the drugs tested.
These scientists are not using those terms in the manner which many bodybuilding authors do. The anabolic effect is measured by increase in weight of the levator ani muscle in the rat, and the androgenic effect is measured by increase in weight of the seminal vesicles and prostate. These measurements are neither perfectly indicative of muscle-building value to bodybuilders nor to any particular undesired side effect except perhaps prostate enlargement. Despite the limitations of the method, this was the assay method available.
A number of esters of nandrolone were studied, using various single doses, but only the results from a single dose of 1 mg are given here. The results are as follows:
Parent Drug
Ester
# of Carbons
Anabolic Effect
Anabolic / Androgenic Ratio
PRC** (P) x10-3
Nandrolone
formate
1
1176
13:1
15*
acetate
2
1594
11:1
25*
propionate
3
1880
10:1
41*
butyrate
4
1488
7:1
69
valerate
5
2526
9:1
115*
hexanoate
6
3731
9:1
192
heptanoate
7
6559
13:1
269
octanoate
8
5557
15:1
611
nonanoate
9
5080
19:1
455
decanoate
10
7735
25:1
802
undecanoate
11
6576
32:1
1460
*extrapolated from P of the butyrate ester
** partition ratio coefficient
The anabolic effect was found to be predictable according to the equation:
log (anabolic effect) = 7.33 log P – 0.636 log P2 –17.8
The accuracy of predictions was quite high (r = 0.970) and the F value, indicating the statistical significance of the equation, was very high at 61. Thus, the observed anabolic effect of these ester prodrugs of nandrolone was found to be highly correlated with partition coefficient.
Higher partition coefficients were also strongly correlated with higher anabolic/androgenic ratio.
It was also found that the times of first and second peaks of drug level after injection were predictable from P with good accuracy and high significance.
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How can the greatly higher anabolic effects of the long chain esters be explained?
While the authors do not make note of it in either article cited, there is a simple explanation for the observed result. Long chain esters of anabolic steroids are not many more times potent than short chain, if indeed they are any more potent at all. Yet in the above study, the undecanoate ester was found to give 3.5 times the effect of the propionate ester. Why?
There is a difference in pharmacokinetics (the time course of the drug in the body). Although the same 1 mg dose is being given in each case, it is either present in the serum of the animal at a relatively high concentration for a relatively short time for the shorter chain esters, or at lower concentration for a longer time for the longer chain esters. This difference can be quite large: the undecanoate ester can be predicted to have a half-life 36 times longer than that of the propionate ester.3
With most drugs, response is not proportional to the dose, but to the log of the dose. Assuming that the dose is well into the effective range, taking ¼ the dose does not result in only ¼ the result, but in ½ the result.
Viewed in this light, if the nandrolone propionate had been given in 36 divided doses over the same length of time that nandrolone undecanoate was in the system, in a manner to match its pharmacokinetics, one would expect 1/6 the result from each individual dose before accounting for molecular weight differences. The cumulative response would be 36 times 1/6, or six times the observed result from the single large dose. If we then correct for the lower molecular weight of the propionate ester, which delivers more nandrolone per mg. than does the undecanoate ester, we would predict 3.3 times more response than from the single large dose. In fact the observed response of the undecanoate ester was 3.5 times that of the propionate ester. This difference is within experimental error.
This calculation I have performed is also supported by experimental evidence performed by van der Vies4. His research showed that when the dose of nandrolone was divided into frequent small injections in such a pattern as to mimic the pharmacokinetics of esters, the anabolic effect became identical to that of the esters.
Thus, pharmacokinetics, the log dose/response curve, and differences in molecular weight are sufficient to account for observed differences in anabolic effect between different esters of an anabolic steroid, or between an ester and the parent drug.
This correlates with my observation that anabolic effect of testosterone esters is equal, so long as each is administered reasonably frequently: at least once per half-life, and preferably twice. E.g., if testosterone propionate yielding some given amount of testosterone per week is administered daily, or at least every other day, it will give results comparable to testosterone cypionate administered at least once every week, and preferably twice per week, that yields the same amount of testosterone per week.
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How can the differences in anabolic/androgenic ratio be accounted for, and how significant are they?
Partition coefficient is key information for determining how a drug will be distributed in the body. The ratio of solubility between oil and water gives good relative predictions of the ratios of solubility between blood and target organs. Different target organs, for example the levator ani muscle vs. the prostate, may have different solubility properties. A more lipophilic drug (one with a high partition coefficient) would distribute much moreso into a more lipophilic target organ than into a less lipophilic one. It may then be the case that the longer chain esters partition more preferentially into muscle and less preferentially into the skin and prostate, but this is not demonstrated.
For this to be the case, it would be necessary for the esterified steroids to be distributed throughout the body after slow release from the oil depot injection site, rather than to have only free parent drug released from the injection site. This is an agreement with the findings of James et al.3 which demonstrate that the esters do indeed become distributed throughout the body after injection.
I don’t, however, expect that differences in distribution are the primary reason for observed differences in anabolic/androgenic ratio between different steroid esters. There is another possible explanation for differences in this ratio. In the same work referenced above concerning anabolic effect as a function of pharmacokinetics, van der Vies showed that if nandrolone is administrated with frequent dosage patterns designed to give the same trend of serum levels as seen with either phenylpropionate or decanoate, nandrolone itself gave the same anabolic/androgenic ratios as each of these esters of nandrolone.
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What application does this information on anabolic/androgenic ratio have to female bodybuilding?
Since keeping androgen levels constant and moderate gives a higher anabolic/androgenic ratio than using the same total amount of drug per week but allowing levels to spike and then subside, female bodybuilders are better advised to use either long acting esters, or if short acting esters are used, to inject small doses frequently (twice per half-life). And for the same reason, a given amount of oral steroids per day is better taken in divided doses than in a single larger dose.
This is probably because tissues with sex-specific traits exhibit thresholds to effect of androgens. Below the threshold, nothing happens, but above it, cellular differentiation occurs. Thus, while female levels of androgens are about 10% that of a male's, 10 years of female levels of androgen will not grow as much beard or change the voice as much as one month of male levels. The threshold simply is not crossed at the lower levels, but is crossed at the higher levels.
Female bodybuilders will do better to avoid spikes in androgen level that cross this threshold. Therefore, consistent low doses are better than spiking with intermittent high doses, and advice to use 100 mg/week of testosterone propionate to avoid virilization simply makes no sense (and in practice, often fails.)
It should still be noted that some women will suffer virilization with almost any dose of anabolic steroid, regardless of dosing pattern.
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What are the half-lives of different esters?
Shorter chain esters have shorter half-lives, because of their lower partition coefficient. Testosterone cypionate has a half-life of 8 days5, the enanthate ester has a half-life of 4 days6, and nandrolone decanoate has a half-life of 8 days7. These figures are only approximate. The difference between these values for cypionate and enanthate probably includes difference attributable to different measuring techniques. The actual difference is probably not more than two days.
In the rat, where half-lives of anabolic steroid esters are similar to those in humans but somewhat shorter, the half-lives of the phenylpropionate, decanoate, and laurate esters are 1, 5, and 10 days respectively.3 The same trend would be expected in man.
Half-life is linearly related to log partition coefficient, which is itself linearly related to the carbon chain length, the exception being if the ester is an unusual one such as phenylpropionate. This was shown by James et al.3 for the formate through valerate esters of testosterone in the rat. The half-life of testosterone propionate was approximately 4 days, and each carbon added to or subtracted from that chain length changed half-life by about 1.5 days.
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How are steroid esters made, and can esters be made of prohormones?
The most convenient method of synthesis of steroid esters is reaction of the steroid in a 2:1 mixture of pyridine and the anhydride of the desired ester: for example, propionic anhydride would be used to make the propionate ester. A large excess (at least 10 times) of the anhydride compared to the steroid would be required. This would then be purified by diluting with at least 10 parts of water to each part of pyridine, adding 1 part ether, decanting the water after shaking, and then washing with 10 parts water repeatedly in a separatory funnel. This would be followed preferably by recrystallization or chromatography for purification.
Esters cannot be made of dione prohormones because they do not have an –OH group. Esters can be made of the diols, but purification by recrystallization probably is not possible because the product would be a mixture of 3a and 3b esters, which could be expected to yield an oily mess, or perhaps an amorphous solid. Further difficulties would include the fact that for the diols, the starting material from at least some manufacturers is of considerably less than 100% purity. I personally would not even consider injecting the product of the above reaction without some further purification besides the water wash. An even more serious consideration is that by esterifying the prohormone, one is arguably manufacturing a controlled substance. To say the least, this is a real no-no with the Drug Enforcement Agency, even moreso than possession or importing, both of which are already quite serious crimes. Therefore I cannot recommend manufacturing esters of diol prohormones, but for the sake of completeness in an article on steroid esters, I thought I would mention how they can be made and what the difficulties are.
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Can we make esters of Winstrol, Dianabol, etc., for injection?
While there are a number of interesting oral steroids that, at first glance, would be appealing candidates for making esters, in fact there are very good reasons why no such products are available. Indeed, there are absolutely no 17-alkylated steroid esters on the market.
First, they would be difficult to synthesize. The 17-methyl group which works to block liver enzymes from reacting with the steroid molecule will also hinder the material one would use to make the ester from reacting with the steroid.
More seriously, there is the fact that a 17-methyl would also block enzymes in the body from hydrolyzing (removing) the ester, which would be necessary to yield the active steroid.
So I do not expect that you will ever see esters of Winstrol, Dianabol, or any 17-alkylated steroid on the market, and don’t recommend that anyone try making them. They would probably be inactive, or if they have any activity, it would be very low.
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Summary, and Practical Implications
Shorter chain esters must be injected more frequently than longer chain esters if consistent blood levels are desired. Consistent blood levels probably lead to the greatest efficiency of use for the drug and the highest anabolic/androgenic ratio. The activity of long chain esters can be mimicked by frequent administration of short chain esters.
While it has been alleged popularly that some esters aromatize more than others, there is no support for this in the scientific literature, and the concept makes relatively little sense since the ester itself is very far removed from the site of reaction of aromatization. The claims in this area seem flawed: for example, in World Anabolic Review 1996, the text makes plain that the comparison being made is between a weekly dose of 350 mg of testosterone propionate vs. a weekly dose of over a gram of testosterone enanthate or other long chain esters. While it is surely true that, as they say, side effects of the latter will be more pronounced than those of the former, it is unreasonable to attribute this difference to the ester used.
All testosterone drugs aromatize, and if estrogenic effects are not desired, then anti-estrogenic agents should be used for any of the esters and in the same manner, regardless of the ester used.
While the theory of the effects of esterification of steroids is interesting and somewhat complicated, the practical implications are simple. Differences between parent drugs are far more important than differences between esters of the same drug. And if the ester is different, the key difference to the bodybuilder is in half-life of the drug. Longer half-lives add convenience, and shorter-half lives allow the drug to exit the body more quickly. Short half-life also can allow fairly rapid drug clearance to occur before drug testing. Testosterone propionate is therefore a drug of choice for the tested athlete. And if a brief alternating cycle plan is being used, a short half-life allows high dosing during the "on" weeks with rapid clearance to non-inhibiting levels during the off weeks. Besides these things, however, there are no significant differences between drugs resulting from use of different esters.
(A shorter version of this article previously appeared in Peak Training Journal. New information has been added for MESO/Rx.)
References:
1. Chaudry, M.A.Q.; James, K.C.; et al. J. Pharm. Pharmac., 1976, 28, 882-885
2. Chaudry, M.A.Q.; James, K.C. J. Med. Chem., 1974, 17, 157-161
3. James, K.C.; Nicholls, P.J.; Roberts M. J. Pharm. Pharmac., 1969, 21, 24-27
4. van der Vies, J. Acta Endocrinologica., 1985, 271, 38-44
5. United States Pharmacopeial Convention, USP DI: Drug Information for the Health Care Professional, 1993, 108. Rand McNally, Taunton Mass.
6. Weinbauer, G.F.; Jackwerth, B; et al. Acta Endocrinol. Copenh., 1990, 122, 432-42
7. Belkien, L.; Schurmeyer, T.; et al. J. Steroid Biochem., 1985, 22, 623-629
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Hier de originele thread.
. Komt er in ieder geval op neer dat middel A middel A is, welke ester er ook aan hangt. De werkzaamheid verschilt niet, zolang de bloedwaarden op een gelijk peil worden gehouden. 
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