Prohormones of Anabolic-Androgenic Steroids

written by Bill Roberts

The modern hormone supplement market, as distinct from the older market for glandular products which were largely ineffective, may be considered to have started in 1996 when DHEA was introduced. This compound is both a prohormone of testosterone and estrogen, and is a hormone in its own right. However, it is rather useless for helping lifters add muscle.

Shortly after the introduction of DHEA, Patrick Arnold introduced androstenedione, a prohormone of testosterone (and, unfortunately, also of estrone, which is an estrogen) to the world of bodybuilding. Prior to this the athletic use of this compound was little known. He followed this with introductions of androdiol, a direct prodrug only of testosterone not estrogen, and norandrodiol.

The prohormones introduced by Patrick Arnold all are "4" compounds: we will discuss the meaning of this later. Others have since introduced some "5" compounds, which we shall also discuss further on. There are now at least five "andro" products on the market.

It then has become rather difficult for the consumer to keep track of which product is which. Androstene? Androdiol? Norandrostene? What are they, and how do they differ? What benefits do they offer? What risks do they have?

These products are very interesting to people who are hoping to gain muscle mass or strength. Generally, the andro supplements increase blood levels of testosterone. They also seem to increase sex drive for many users.

On the other hand, these products have side effects that everyone should be aware of. Women in particular should know that use of any andro products can lead to unwanted side effects such as facial hair growth. These products are precursors of male sex hormones, and so women should at the least give the matter careful and informed thought before using them. Using doses anywhere near what is appropriate for males is likely to lead to some masculinization: for example, a lowering of the voice or an increase in facial hair. A problem is that women vary a great deal in susceptibility and so no particular number larger than zero can be given as a dosage that is safe for all women.

All of the andro products are steroid molecules which are very similar to testosterone, the principal male sex hormone. When taken orally, they result in brief increases in blood testosterone levels.

The norandro products, instead of being similar to testosterone, are similar to nortestosterone. This compound is also called nandrolone, and, interestingly, is a sex hormone found in certain animals including horses, but (contrary to claims by some) not in humans. This steroid is anabolic in humans, but in men often has the unfortunate effect of producing partial or complete impotence, which is reversed on cessation of use.

The body has enzymes to convert steroids from one form to other similar forms. Testosterone has three features which may be changed by enzymes. When any of them are changed, a different steroid results. Enzymes often work two ways, though. As it happens, if an enzyme can convert testosterone to another andro, say to androstenedione, then it can also convert that steroid back to testosterone.

Let's start with androstenedione, often called simply androstene.

This steroid is exactly the same as testosterone in every way but one. Where testosterone has a hydroxyl group in a certain position, androstene has a keto group. All the rest of the steroid is exactly the same. So the body can convert testosterone to androstene back and forth by using the enzyme that can make this change. This enzyme is called 17b -HSD and is present in the body in fairly large amounts.

It would be illegal for a supplement retailer or distributor to sell testosterone capsules. But it is legal for them to sell androstene capsules.

The androstene, when taken up into the body, can be and is converted to some extent to testosterone. The percentage that is actually converted to testosterone is fairly low. For a man, a dose of 100 mg might increase blood testosterone levels by 50% or less for a couple of hours. For a woman, the percentage increase would be much higher, since they are starting from much lower levels. (Women have only about 1/10 as much natural testosterone as men do.)

Does this brief, fairly moderate increase in testosterone really help build muscle? The jury is out on that one. Many athletes feel androstene improves their workouts and like using it. Others have found the only noticeable effects to be undesired side effects, and therefore have been unhappy with this supplement. Most of those who claim excellent gains are very heavy users who take the supplements many times per day – however, such usage shuts down natural testosterone production which will then take some time to return to normal after stopping usage, even if the usage is only for a few weeks. This is something that preferably should be avoided.

Androstene is the product that consumers are most familiar with, since it has been on the market the longest. But now we have 4-androstenediol (androdiol), 5-androstenediol (5-androdiol), norandrostenedione (norandrostene), and 4-norandrostenediol (norandrodiol). Keeping track of which is which and understanding the differences is not difficult if we remember the three ways that steroids can be interconverted with testosterone by enzymes. It then becomes easier to understand how these differ and why we might prefer one of them over others.

We already mentioned the first way an enzyme can change one steroid into another. This was interchanging the keto that androstene has at the 17th position with a hydroxyl by 17b -HSD. Both of the diones (androstene and norandrostene) rely on this conversion. Both use this enzyme, and a small fraction of each is converted to testosterone or to nandrolone, respectively.

The second way is interchanging the hydroxyl that a diol has at the 3rdposition with the keto that testosterone has by another enzyme, 3b -HSD. Both of the diol products rely on this. So androdiol and norandrodiol both use this enzyme, and again, a small fraction is converted to testosterone or nandrolone, respectively.

The third way involves changing bonds as well as groups. While testosterone has a double bond (a chemical bond between carbon atoms using two pairs of electrons rather than just one pair) between the 4- and 5- carbons, the 5- prohormones have their double bond between the 5- and 6- carbons. These, such as 5-androstenediol, can only be converted to testosterone if this bond is changed in the process. This is more complex, and requires 3b -HSD/5,4 isomerase. The net result though is the same thing: conversion to testosterone.

Compared to DHEA, all of the andro products are more easily converted to testosterone. DHEA must first be converted to androstene before it can be further converted to testosterone. Generally, DHEA use does not result in significant increases in blood testosterone levels, even at 1600 mg/day. It can, however, result in increased local levels of testosterone in tissues where the conversion enzymes are plentiful. This includes the skin. For this reason, DHEA use, like andro use, can cause facial hair growth in women. But DHEA is more or less useless for building muscle. It may have other benefits for older individuals at doses such as 50 mg per day, however.

Many enthusiastic users feel that taking andro products "just stimulates the body to produce more testosterone" and they feel that this is a good thing. But that is not what is happening. The enzymatic conversion of the supplements does not occur in the testes, and natural testosterone production is not increased. To repeat: these products do not increase natural testosterone production.

Long term, heavy use of these products will decrease natural testosterone production. If blood levels of testosterone are kept artificially high by supplements, natural testosterone production will be reduced to compensate. However, if the andro products are used moderately, this may not occur. There is no scientific answer yet that shows just how much use is moderate. I have found that users who have followed my advice not to use these products in the evening or at night have not had problems in this area, while those that choose to use them in the evening do have problems. This is probably because there is a natural daily rhythm to testosterone levels and production. Levels fall off at night, which causes increased production of the hormone (LH) that causes the testes to produce more testosterone, which then causes levels to become high again by the next morning. As a result, higher testosterone levels during the day don't result in much loss of production, but high levels at night result in the body producing less LH and therefore less natural testosterone.

What about side effects? And how should one choose between these different products?

The diol products result in higher testosterone levels for the same dose than the dione products -- they seem to be about three times more effective. Since different enzymes are used for the diol and dione products, some people speculated that combining the two types of supplements could give the most results. However, since the diols work so much better, the answer probably simply is to take more diols.

The 5-androstenediol product looks like a bad bet for men. It is not only an androgen but is also an estrogen, which suggests that this product may be more likely to cause gynecomastia (abnormal growth of breast tissue in men).

Androstene itself is normally present in the blood in both men and women. It is thought to itself be inactive, or of very low activity, until converted to testosterone. But testosterone, when present in higher than normal levels for sustained periods of time, can have side effects. For men, these can include male pattern hair loss and prostate enlargement. If testosterone levels are raised, then some of this testosterone will, unfortunately, be converted to estrogen, and this can lead to gynecomastia. Androstene itself can also be directly converted to an estrogen. In fact, androstene is more easily converted to an estrogen than testosterone is. Therefore, one gets benefit from only the relatively small amount that converts to testosterone, but suffers side effects even from that which does not convert. Androstene is a particular culprit for causing gynecomastia.

For women, increased testosterone levels, or increased levels of any androgen including nandrolone, can lead to an irreversible increase in facial hair, deepening of the voice, change in skin texture, and enlargement of the clitoris. Both sexes may experience acne or hypertension from these products.

We don't know if all of these side effects may be seen from occasional use of the andro products. However, acne and hair loss problems have been commonly reported. Men using androstene have also reported gynecomastia.

The norandro products offer the potential of lessening these side effects, because they cannot be converted to testosterone. Instead, they are converted to nandrolone. This steroid is much less likely than testosterone to cause hair and skin problems. Also, norandrostene is less able than androstene to be converted to estrogen, so it may be less likely than androstene to lead to gynecomastia. For women that conversion is not a disadvantage, and the nor products offer the advantage of giving a better ratio of muscle-building effect to undesired side effects. Even so, for many women some virilization will result from any dose that is effective for building muscle.

Therefore, the norandro products may be considered probably safer than the andro products. They have not been on the market long enough, though, for this to be certain. Norandrostene, though, has been reported by some users to interfere with erectile function, and norandrodiol may also have this problem.

Which of these products is best?

In my opinion, each of the diols is clearly superior to the corresponding dione: androdiol is better than androstene and norandrodiol is better than norandrostene. The diols are more effective and much less likely to cause gynecomastia, because the diols cannot be directly converted to estrogen. With the diols, conversion can occur only with that fraction that first converts to testosterone, which is much less than the full amount.

For women, some users claim the diones appear comparably effective to the diols. This may be because women have higher levels of the necessary conversion enzyme for the diones. Women who wish to use these products might then consider either norandrodiol or norandrostene, while men should in my opinion favor androdiol or norandrodiol.

But if the diols are better for men, then which of them is best for these users? I think the answer is: it depends. If one wants the most effect for the money, the clear answer is androdiol. If however, one wants the least effect on skin, hair, or prostate, norandrodiol is the better choice.

How much to use? Opinions vary but my opinion is 300 mg at a time, no more than three times per day, with the last dose preferably no later than 4 or at the most 6 PM. Aparticularly good time to take androdiol is 1-2 hours before a workout, since this will cause testosterone levels to peak during the workout, which does make a noticeable difference in how one feels in the gym and how well one can perform. I think that an ideal pattern of usage would be to use for only two weeks at a time, then taking two to four weeks off before using the products again.

Another method that would be acceptable would be to use andros for up to 8 weeks, then to take at least 4 weeks off, and resume only when confident that natural testosterone levels have been returned to normal for at least two weeks (this might require many weeks of waiting if the user does not follow the advice not to use these supplements in the evening.) This can be judged fairly well by sexual performance.

Those who wish to obtain effects similar to say a weak AAS cycle, rather than simply an "edge" in their training, will have to use the products heavily, unfortunately. Personally I would consider pharmaceutical AAS to be the better route if legal and available. I am not sure that there is any way to get greatly increased gains relative to the natural state if testosterone levels are raised only half of each day, as is the case with a usage pattern designed to minimize inhibition. The products still have some benefit with conservative use, but gains will not be drug-like.

How about delivery methods? Capsules taken orally have been used the most and are the most convenient. It is a good idea to open the capsules and mix the powder with liquid, because sometimes the capsules don't digest well. All andros should be taken with a little oil -- a tablespoon will suffice -- or with a meal that naturally contains a little fat. Ten grams is enough. This is because the andros are not water soluble but are somewhat soluble in oil.

Transdermal products are becoming available, but are inconvenient and furthermore have the disadvantage of delivering the product slowly and steadily over relatively long periods of time. This means that one cannot have high levels specifically during one' workout, or just during the day but not at night: one is going to have the same levels all the time. This means that if enough is being used to be effective in helping build muscle, it will also be effective in shutting down natural LH production at night. Therefore, I don't recommend the transdermals unless one is willing to sacrifice natural testosterone production. If someone wants gains at all costs, including shutdown of natural testosterone, then the transdermal products, particularly in combination with heavy oral or sublingual use, would make sense. A cycle of pharmaceutical AAS would make more sense though.

Sublingual delivery has just been introduced. This is an effective way of getting the same effect from a much smaller amount of andro. So when comparing price, 25 mg of sublingual androdiol is probably comparable to perhaps 250 mg or so of androdiol in a capsule. I would expect the duration of action to be a little shorter.

None of these products will build muscle unless a good weight training program is being followed, and they are all usually rather pointless unless someone has been following such a program consistently for at least a year. Prior to that, good gains should be made without using any such product -- if andro supplementation seems necessary then the problem really is elsewhere: usually in training or in diet.

For those who are particularly cautious, it should be noted that no clinical studies been done on the safety of any of these supplements, since they are not being sold as drugs.

And this, in a way, is very surprising. These products convert to testosterone or nandrolone, which legally are anabolic steroids. But because no drug company has sold them as drugs, and they are natural products, they are available for sale as nutritional supplements. As it happens they probably are safe for men for long term use when cycled (using the supplement in some weeks but not in others) and used with moderate doses, because their function is simply increasing what is already a natural hormone in the body, or providing a closely related substance (nandrolone).

Because they are not legally drugs, even though they are steroids, the buyer has the freedom to use these products – but the choice should be made carefully. They can be effective in briefly increasing blood testosterone or nandrolone. Whether this should be done or not is, at least this time, up to the consumer's own personal choice, which, with sufficient information, may very well allow beneficial use of these compounds as ergogenic aids

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