Everything about how Anabolic Steroids work

I’m pretty sure there’s some people reading my blog who don’t know everything about how anabolic steroids work, how they’re metabolized, and all that other fun stuff…So I’m going to try to give an explanation for the people really interested in the science/biology/chemistry behind some of this stuff. Don’t feel like you need to read all of this at once, because it’s a pretty long read (and took me even longer to write), but it’s worth your time to get through all of it.

Part I

As you probably already know, anabolic steroids are drugs that resemble anabolic/androgenic hormones like testosterone, or similar derivations. The defining structural characteristic of all steroids is their four-ring structure, consisting of 3 cyclohexane (6 sided) rings and a cyclopentane (5 sided) ring.
Your body produces various steroids (and so-called pro-hormones) initially from Cholesterol which the body can eventually metabolize into testosterone.

The four-ring structure is called the Steran Nucleus, and for our purposes there are four rings (A, B, C, and D), and 19 total positions on the structure.

Each place where the ring has a “corner”, or is attached to another ring is a “position” on the structure.

The black and white diagram above represents your basic testosterone; the rings run from left to right and are called A, B, C, and D respectively. To create different steroids (testosterone is the one shown above) scientists can add things called carbon bonds, add beta groups, etc, and that produces different steroids. Typically, the A-ring and D-ring are most commonly modified to produce different steroids (with different effects). This is because the A and D rings generally undergo the most drastic metabolation in the body, so modifying them produces more bang for the buck, generally speaking. The B-Ring metabolism is most pronounced when A-ring metabolism is in some way hampered. The changes the B-ring typically undergo are 6b-hydroxylation and 6, 7-dehydrogenation. These changes are, in fact, not very drastic. C-ring metabolism is even more modest, being a simple 12-hydroxylation. If you didn’t catch those last few parts, don’t worry, because they aren’t super-important. Let’s talk about A and D ring metabolism for a second, ok? These are where we need to focus our energies, because understanding them is very important, while B and C ring metabolism is generally very limited, and won’t really be a concern to us at all, in any applicable context. First, A-ring metabolism…

In the A-ring we see 5alpha and 5beta reduction taking place:

And of course, 5alpha Reduction (5a-Reduction) is what turns testosterone into DHT. This is the initial step in metabolism of testosterone and many of its analogues, and basically just reduces the C4, 5 double bond—that’s the little line on the bottom of the first ring that’s missing in the lower left version of that picture above, where the hydrogen (“H”) has “appeared”. As you can see, 5beta-reduction is very similar, though not of prime concern to us here. After this reduction, typically the 3-keto group is transformed. Stability and instability of the 3-keto group is important to androgen binding, and the more stable the 3-keto group is, the more avidly a compound can bind to the Androgen Receptor and/or increase anabolic/androgenic activity (even doing so, in certain cases, independently of each other). Certain modifications to steroids can enhance the stability of the 3-keto group, such as 2-methylation or adding a 2-hydroxymethelyne group (the first modification is seen with Masteron and the second with Anadrol). On the other hand, Ethylestrenol lacks a 3-keto group totally, and is probably the weakest steroid available.

Of course, my example focused on testosterone, and if you add a double bond between the one and two carbon atoms of testosterone, you’ve made Boldenone (Equipoise). Boldenone is metabolized slightly differently since the 1-2 double bonds slows metabolism (hepatic breakdown, aromatization, etc…).

Add a 17-alpha-methyl group to that Boldenone we just spoke of, and you have Methandrostenolone (D-bol), which is broken down similarly, although it is orally active in the body due to the 17a-methly group.

(Note that Dianabol and Equipoise are the same EXACT compound with exception to the methylation you see at the 17^th position for the Dianabol).

There are, of course, other actions that happen (or simply can happen) in the A-Ring, but we need not concern ourselves with them here. It is suffice to say that they are not of interest to us, again, generally speaking.

D-Ring metabolism…

The D-ring (the weird little one on the end with fewer sides than the other rings) is metabolized into testosterone’s main metabolites. This occurs by oxidation of 17b-hydroxy groups into 17keto steroids, which are shown less intricately in the first chart in this chapter. In some cases, they can even be converted back to the original configuration by the same enzyme (17b-HDS).

Hydroxylation can also occur at other positions, as can epimerization, or oxidation, within the D-ring. And remember, the D-ring is where we can methylation them to survive oral ingestion.

All of that was the first phase of anabolic steroid metabolism, which determines the primary effects they will have in the body. Phase II metabolism has more to do with metabolites, their degradation, and the eventual elimination of them and the steroid from the body, and as such is beyond the scope of our discussion here -well…. really, its just beyond the scope of our interest, more or less, because it’s not going to help us understand the anabolic actions of steroids any better. The preceding information should help you later in this book, when I mention that this (or that) steroid has a particular modification to help it do something (or other). I know that once I started understanding a little of what I am presenting here to you, I found it a lot easier to comprehend what was going on when I looked at a steran nucleus or chemical name for a particular steroid.

Synthetic anabolic steroids are based on the principal male hormone testosterone, modified in one of three ways:

• a. Alkylation of the 17-carbon (makes them survive oral ingestion)
• b. Esterification of the 17-OH group (alters active life and half life)
• c. Modification of the steroid nucleus (changes their properties)

Part II

Despite the number of synthetic AAS that have been developed by these little modifications here and there, their modes of action are still poorly understood.

As you know, male hormones, primarily testosterone, are responsible for the developmental changes that occur in boys during puberty and later in adolescence. Male hormones have both androgenic and anabolic effects. Androgenic effects are changes in primary and secondary sexual characteristics, like enlargement of the penis and testes, voice changes, hair growth on the face, increased nervous system efficiency, and increased aggressiveness. The anabolic effects of androgens (again, like testosterone) include increasing and limiting muscle protein synthesis by increasing transport of amino acid across cell membranes. It is also an anti-catabolic and inhibits cortisol by competing for receptor sites, as well as reducing cortisol secretion and the signals, which precede cortisol secretion. In addition to these anabolic effects, Testosterone increases the secretion of the other anabolic hormones in the “super family”, such as growth hormone and Insulin-Like Growth Factors from the liver, and finally, it produces an enhanced rate of erythropoietin synthesis. All of these effects are, of course beneficial to athletes, and explain how steroids exert their performance enhancing effects.

These effects are mediated, at least partially by stimulation of receptor molecules in muscle cells (which we generally call androgen receptors), which activate specific genes to produce proteins. Binding affinity to the androgen receptor has been used to explain the differences in potencies and effects of the natural and synthetic androgens we talk about, but that isn’t the full story. There are, of course, other effects that steroids exert, and we call those “non-receptor-mediated” effects. These are effects that happen indirectly, and not as a result of androgen receptor stimulation. Stimulation of the androgen receptor produces both anabolic and anti-catabolic effects, such as the retention of more nitrogen and the reduction of cortisol, respectively. Remember, Cortisol causes muscle breakdown.

Sounds great, right? It’s everything we want and more! It’s not all roses, however, because Anabolic steroid use decreases testosterone secretion. This happens because your body operates on a negative-feedback-loop in regards to testosterone. This means we’re going to attempt a balancing act regarding our natural hormones and the ones we put into our body. If you read this book carefully, you’ll learn how to use (or simply research) anabolic steroids to produce a heightened state of athletic ability, strength, speed, and of course, increased muscle mass. Then you’ll learn how to stop using steroids and not lose everything you’ve gained. Those are, at least, my humble goals for you.

So let’s get back to the first thing I told you about, which is how steroids are made. As you saw, simple modifications to the four-ring steran nucleus of testosterone can produce major changes in the hormone. From those simple changes to testosterone, scientists have identified the other two major families all anabolic/androgenic steroids are derived from: 19-nor-Testosterone (sometimes called 19-nor’s) and dihydroTestosterone (called DHT).

19-nor-Testosterone is simply testosterone that lacks a carbon atom in the 19^th position, and Dihydrotestosterone is Testosterone that has had 2 hydrogen atoms added to it.

In general, 19-nor derived steroids exhibit a high anabolic effect and a low anabolic effect with not much aromatization, while DHT-derived steroids usually have a very nice balance of androgenic and anabolic effects and not much aromatization.

Of course, there are also other things you can do to steroids like methylate them (this makes them able to survive oral administration) or add an ester to them (this is a large fatty chain on a steroid that your body needs to work to break down, thus increasing the active life of the steroid). Adding an ester to a product doesn’t change its anabolic: androgenic ratio, but methylating it may. Esters do not alter the anabolic or androgenic properties because an ester is simply a chain composed primarily of carbon and hydrogen atoms, typically attached to the base steroid hormone at the 17th carbon position (called the beta position). Attaching an ester to a base compound slows the release of the base steroid from the site of injection.
Slowing the release of the base steroid is a great benefit to medicine, especially hormone replacement therapy (HRT) because suspended or free testosterone (or other steroid hormones) would only remain active in the body for a very short period of time. This is basically what is seen with testosterone suspension or Winstrol depot. If you are on HRT, you could take a shot of Testosterone Cypionate (testosterone with a long ester added) once a week, as opposed to taking testosterone suspension once or twice a day. Adding an ester also temporarily deactivates the steroid molecule. With an ester chain blocking the 17th beta position, binding to the androgen receptor is not possible, so the steroid is inactive. Now, in order for the base compound to become active, the ester must first be removed. This occurs once the compound has filtered into blood circulation, where your esterase enzymes cleave off the ester. This restores the necessary hydroxyl (OH) group at the 17th beta position, which enables the drug to attach to the receptor. Now the steroid is free to do all the good stuff we want it to do. This is why people often say, “test is test,” regardless of the ester; regardless of the ester, anabolic and androgenic properties of the base compound retain their respective integrity.

You may, at this point be asking yourself how these anabolic to androgenic ratio’s are arrived at. Well, this is kind of weird, but basically, male rats were given a dose of testosterone, sacrificed (killed to you and me), and then had an untrained muscle (the levator ani), and a part of the prostate (the ventral prostate) weighed. Those weights were given a score of 100 each (because 100 is an easy number to work with). When you want to know the anabolic: androgenic ratio of a new steroid, you simply administer it to a group of rodents with the same dose of testosterone used in the original group of rats I just told you about. You then weigh the levator ani and ventral prostate. The weights that are relative to testosterone (and it’s 100 score) are the anabolic: androgenic ratio of the new steroid. Of course, that’s not 100% relevant or applicable to humans.

By tweaking and refining steroids, scientists were able to create some very interesting compounds that have some profoundly beneficial effects to us as athletes. And now you know (roughly) how it’s done, and how steroids work.

NOW YOU KNOW!