Testosterone Esters and Derivatives

Testosterone Esters and Derivatives

Testosterone esters have increasingly been used in replacement therapy, but abuse of these compounds has risen as well. A feature that all testosterone esters have in common is a testosterone molecule with a carboxylic acid group (ester linkage) attached to the 17-beta hydroxyl group. These esters differ in structural shape and size; they function only to determine the rate at which the testosterone is released from tissue. Generally, the shorter the ester chain, the shorter the drug's half-life and quicker the drug enters the circulation. Longer/larger esters usually have a longer half-life and are released into the circulation more slowly. Once in the circulation, the ester is cleaved, leaving free testosterone.

Common testosterone preparations include the following:
Testosterone esters

Testosterone propionate
Testosterone cypionate
Testosterone enanthate

Testosterone derivatives

Methyltestosterone

Methyltestosterone is a very basic anabolic-androgenic steroid (AAS), with the only addition being a methyl group at C-17. This eliminates first-pass degradation in the liver, making oral dosing possible. It also causes dose-related hepatotoxicity.

Methyltestosterone is metabolized by aromatase to the potent estrogen 17-alpha methyl estradiol and is also reduced by 5AR to 17-alpha methyl dihydrotestosterone.

This compound exhibits very strong androgenic and estrogenic side effects and is generally a poor choice for most, if not all, uses.

Methandrostenolone

Methandrostenolone has an added cis- 1 to cis- 2 double bond that reduces estrogenic and androgenic properties. However, it does undergo aromatization to the rather potent estrogen 17-alpha methyl estradiol, but curiously, it does not show the in-vivo propensity for reduction by 5AR to alpha dihydromethandrostenolone to any large degree.[10]

This steroid was first commercially manufactured in 1960 by Ciba under the brand name Dianabol and quickly became the most used and abused steroid worldwide, remaining so to date. It jokingly came to be known as "the breakfast of champions" in sports circles.

This agent is very anabolic, with a half-life of approximately 4 hours. The methyl group at C-17 makes this AAS an oral preparation and potentially hepatotoxic.

Ciba, as well as generic firms in the United States, discontinued methandrostenolone in the late 1980s, but over 15 countries worldwide still produce it in generic form.

Fluoxymesterone

Fluoxymesterone is a potent androgen that is produced under the brand name Halotestin. It is an excellent substrate for 5AR and conversion to dihydrotestosterone (DHT) metabolites. With the addition of a 9-fluoro group, it is a very potent androgen that has little anabolic activity. An added 11-beta hydroxyl group inhibits its aromatization. Again, the C-17 methyl group makes oral administration possible, but with hepatic concerns.

This AAS is not favored in clinical practice due to its poor anabolic effects, yet athletes abuse it for its androgenic nature and lack of peripheral aromatization.

Nandrolone derivatives [11]

Nandrolone decanoate

Nandrolone decanoate is simply a 19-nortestosterone molecule in which a 10-carbon decanoate ester has been added to the 17-beta hydroxyl group. This addition extends the half-life of the drug considerably. Nandrolone (19-nortestosterone) is a potent anabolic with a relatively favorable safety profile. Nandrolone is reduced by 5AR in target tissues to the less potent androgen dihydronandrolone. Its affinity for aromatization to estrogen is low, being perhaps 3-4 times less than that of testosterone.[12]

Nandrolone and its several esters (decanoate, phenylpropionate) differ only in their half-lives, due to the difference in ester properties.

Nandrolone is a relatively safe drug with minimal androgenic concerns and ample anabolic action at therapeutic doses. Nandrolone decanoate is an intramuscular (IM) preparation and lacks the hepatotoxic C-17 group; however, this agent is one of the most widely abused AASs, due to its efficacy, safety profile, and worldwide manufacture.[13]

Ethylestrenol

Ethylestrenol is an oral 19-nortestosterone derivative and was marketed in the United States under the brand name Maxibolin, but it has since been discontinued.

This agent differs from nandrolone by the addition of a 17-alpha ethyl group to reduce first-pass metabolism, as well as by the deletion of the 3-keto group. This latter omission seems to reduce androgen receptor binding.

Ethylestrenol is a mild AAS, having very little anabolic or androgenic effect at therapeutic doses.

Trenbolone

Trenbolone is a derivative of nandrolone with several additions. The addition of a cis- 9 to cis- 10 double bond inhibits aromatization, while a cis- 11 to cis- 12 double bond greatly enhances androgen receptor binding.

This drug is androgenically and anabolically potent. It is comparably more androgenic than nandrolone due to its lack of conversion to a weaker androgen by 5AR, as is seen with nandrolone.

Trenbolone is a European drug with a very high abuse record. In the United States, it is used in veterinary preparations as trenbolone acetate; as such, it has found its way into the hands of persons who wish to exploit its androgenic and anabolic potential.
DHT derivatives

Oxandrolone

Oxandrolone, a derivative of DHT, is C-17 methylated, making it an oral preparation.

The second carbon substitution with oxygen is thought to increase the stability of the 3-keto group and greatly increase its anabolic component. This AAS is very anabolic, with little androgenic effect at a therapeutic dose. 5AR does not reduce oxandrolone to a more potent androgen, and as a DHT derivative, it cannot be aromatized.

First marketed by Searle, DHT was discontinued in the mid-1990s. BTG remarketed this AAS as Oxandrin, largely for the drug's use in HIV-related disease.

Due to its mild androgenic properties, oxandrolone is one of the few agents to be routinely abused by female athletes. Athletes, from weightlifters to boxers, use oxandrolone, seeking to increase strength without experiencing additional weight gain.

Stanozolol

Stanozolol is an active AAS, due to the stability afforded by the 3,2 pyrazole group on the A-ring, which greatly enhances androgen receptor binding. The C-17 methyl group enhances oral availability.

Stanozolol is highly active in androgen- and anabolic-sensitive tissue. It is a weaker androgen than DHT and exerts comparatively less androgenic effect. It will not aromatize to estrogenic metabolites.

This AAS, marketed in the United States and abroad as Winstrol, comes in oral and injectable forms.

Athletes, many in track and field, have abused it. In 1988, Canadian sprinter Ben Johnson was stripped of his Olympic gold medal after testing positive for stanozolol.

Oxymetholone

This quite potent AAS is a unique agent. Oxymetholone is C-17 methylated and, thus, is an oral agent. The 3-keto stability added by the 2-hydroxymethylene group greatly enhances the drug's anabolic properties. The action of this agent in androgen-sensitive tissues is much like that of DHT and is quite androgenic.

Oxymetholone is the only AAS to date to be considered a carcinogen.[14]

Like this entire class, oxymetholone does not aromatize. It is thought to activate estrogen receptors via the 2-hydroxymethylene group, and it can exert many estrogenic side effects.

Oxymetholone is marketed in the United States as Anadrol-50 and has been abused the world over by weight lifters and strength athletes for its strong anabolic and pronounced androgenic effects.

Very good information.