Prohormones/Testosterone, is this 100% accurate from experience?

[WAK]

I found this article by Patrick Arnold, do you agree with this 100%? If not please advise your experience. Thanks in advance.

Many of you have heard Patrick Arnold's name mentioned in one or more of the Internet chat rooms devoted to performance enhancement. Then again, you might have seen him interviewed on one or more of the major networks in the last couple of months. Why is his name being bandied about almost as much as Monica Lewinsky's? Well, when some news reporters were interviewing major league home run king Mark McGwire this past baseball season, they noticed a bottle marked "Androstenedione" in his locker. A few reporters did some basic research and they went nuts. What they found was that the "supplement" was a steroid —a legal steroid, but a steroid nonetheless.

As news reporters are wont to do, they sought out an expert on the subject; the expert. That's right, they went to Patrick Arnold. He's the chemist generally credited with bringing the product to the US market. Since then, Arnold has developed products that make plain ol' androstenedione look primitive. Trouble is, every other Tom, Dick, and Harry has also entered the Andro Wars, each claiming that their product is the best.

Well, you know something? We don't believe every Tom, Dick, or Harry. We believe Patrick Arnold. Here's his take on the subject:


Tell me the truth. You're a little confused about androstenedione and all the rest of the prohormones, right? I mean, with all the diones and diols, andros and 19-norandros, 4's and 5's floating around, you almost need a degree in biochemistry to make sense of it all!

Well, I'm going to give you my take on the subject. I think I've got the evidence to convince you, once and for all, that one prohormone in particular is the right choice. Granted, I discovered this particular prohormone and introduced it to the public. I also manufacture the product. Try to put that fact aside for a moment and let the evidence speak for itself. I firmly believe that, as time goes by, and the confusion starts to fade away (if that's even possible), this particular prohormone will emerge as the top dog in the field.

I almost feel like asking for a drum roll, but the king of the prohormones is a steroid known as 4-androstenediol, or Androdiol®.1 It's a direct precursor and metabolite of testosterone . You might not have heard of 4-androstendiol (also abbreviated as 4-AD) because it's not a common androgen metabolite and, as such, isn't discussed in the literature as much as androstenedione and DHEA. However, it's formed in several tissues, such as placenta, uterus, testicles, adrenal cortex, hypothalamus, and pituitary, but it doesn't stick around very long because it quickly converts to testosterone.2

For those of you who have at least a little bit of a chemistry background (or even care), it converts via the enzyme 3beta-hydroxysteroid dehydrogenase (3beta-HSD). The conversion is rapid and much more efficient than that of other prohormones, resulting in considerably more testosterone production. Take a look at the following comparison of the conversion rates of various prohormones:

Compounds and Percent Testosterone Formed*

DHEA: 0.35%
5-Androstenediol: 0.19%
Androstenedione: 5.61%
4-Androstenediol: 15.76%

*The amount of testosterone formed upon incubation in human blood. (Source: Blaquier, J., Forchielli, E., and Dorfman, R., Acta Endocrinologica, 55, 697-704)


It's no contest. This data shows 4-AD to be far superior to androstenedione in regard to testosterone conversion. To illustrate it another way, 4-AD is 281% more efficient in T conversion than its closest competitor, androstenedione.

Nevertheless, this is in-vitro (conducted in a test tube) data and doesn't necessarily indicate what will happen when living, breathing males ingest it. To answer this question, LPJ Research, Inc. funded a study at Eastern Michigan University that was supervised by Tim Ziegenfuss, PhD. What Dr. Ziegenfuss did was give seven male subjects (average age: 28.1 years) samples of 100 mg androstenedione, 100 mg 4-androstenediol, and 100 mg placebo, all on separate days.

The subjects had a portion of blood drawn before and after ingesting the samples. They continued to have blood drawn at intervals of 30, 60, and 90 minutes. Blood samples were then analyzed for total testosterone and free (unbound) testosterone.

4-AD caused a 310% greater increase (relative to placebo) in total testosterone compared to androstenedione, and a 256% greater increase in free testosterone!

Unfortunately, due to budget constraints at the time, the study was only carried out to 90 minutes, so we don't know how fast the hormone levels declined. However, if you look at both prohormones, it appears that they both share the same pharmacokinetic (rate of rise and fall in levels) properties. This data is scheduled to be presented at a professional conference in Finland this November, and will then be considered a totally valid, peer-reviewed study.


Other 4-Androstenediol Advantages

It's clear that 4-androstenediol raises testosterone levels much higher than any of the other prohormones. However, 4-AD has a couple of other properties that make it superior to androstenedione as well. The first involves conversion to estrogens.

I pointed out that a small percentage of androstenedione gets converted into testosterone. Fine. Trouble is, a percentage of it also gets aromatized (aromatization is the biological process that converts androgens to estrogens) into estrone (an estrogenic hormone). Not good.

To back this up, there's been a growing number of anecdotal reports of mild gynecomastia (gyno, bitch tits) associated with the usage of androstenedione. A lot of young athletes started taking androstenedione in the hopes that they could be like Mark McGwire. They didn't account for the fact that it may be difficult to find a bra that large.

The issue is a complicated one and we still don't understand the exact metabolic fate of ingested androstenedione, but it's apparent that estrogen conversion is a significant problem with this supplement.

Fortunately, 4-AD doesn't suffer from the same drawback. It can't aromatize. It lacks the structural chemical characteristics to do so. The total explanation would be a lengthy one (and a boring one), but suffice it to say that the aromatization mechanism requires a ketone group at the 3-carbon that will enolize in the last step to produce an A-ring aromatization.3 Hey, you asked for it.

Anyhow, testosterone and androstenedione have this 3-ketone, while 4-AD doesn't. All you need to know is that androstenedione (along with 19-norandrostenedione) can convert directly to estrogens while 4-androstenediol (and 19-nor-4-androstenediol) can't.

I should remind you, though, that the testosterone formed from the conversion of 4-AD can itself aromatize. That problem is inherent to testosterone. If you want to raise T levels, you're going to get some aromatization. Nevertheless, the fact that the precursor (4-AD) is unable to do so makes it greatly superior to androstenedione. You won't throw your testosterone:estrogen ratio out of balance with 4-AD.

When I first developed 4-AD, I sent a sample to the owner of a well-known supplement company. He is also one of the first steroid experts to surface in the 80s and co-wrote "The Underground Steroid Handbook." This guy was one of the first to sell androstenedione, but when he tried 4-AD, he was amazed at how effective it was. What he found particularly interesting was the fact that while large amounts of androstenedione would aggravate his pre-existing gyno considerably, equally large amounts of 4-AD didn't. In fact, 4-AD seemed to shrink his nipple lumps. Quite impressive feedback, considering the source.


4-Androstenediol and DHT

DHT is generally a bad word among bodybuilders. It, along with its derivatives (particularly 5alpha-androstan-3alpha,17beta-diol) is linked to undesirable conditions, such as male pattern baldness and prostatic hypertrophy. These compounds are known as 5-alpha reduced androgens and are formed by the enzymatic conversion of androgens such as testosterone.

Well, unlike androstenedione, which can readily convert to DHT and its derivatives (5-alpha reduced compounds), 4-AD doesn't convert to DHT. It can't.

The enzyme 5-alpha reductase is responsible for this conversion. Testosterone, along with androstenedione, can undergo direct 5-alpha reduction. However, by using 4-AD instead of androstenedione, we can once again avoid an undesirable direct metabolic risk. Scientists have shown conclusively that 4-androstenediol is unable to undergo 5-alpha reduction and must convert to testosterone in the body before such a reaction can take place.4

Chalk another victory up for 4-AD.


5-Androstenediol Versus 4-Androstenediol

There's also a lot of confusion about 4-AD and 5-AD. After all, they sound pretty much the same and have similar chemical structures. They do, however, have significantly different biological activities.

Let me first preface this discussion by explaining the difference between "4" and "5" steroids . There are two classes of steroid precursors being sold right now that differ chemically by the position of the chemical double bond in the steroid molecule (hence the "4" and "5" designations). First, we have the compounds which fall into the "DHEA family" of steroid precursors, and that would be the "5" compounds. They are listed below:

5-Steroids

• DHEA
• 5-androstenediol
• 19-nor-5-androstenediol
• 7-keto DHEA
• Pregnenolone


Then, there are the compounds which constitute the "androstenedione family" of precursors, and these would be the "4" compounds:

4-Steroids

• Testosterone
• 19-nortestosterone
• Progesterone
• Androstenedione
• 4-androstenediol


Now, I'm going to get pretty technical here, so bear with me. The most active/effective endogenous androgens (testosterone, nortestosterone) have the C=C double bonds in the 4 position (or have no double bond at all, and a hydrogen in the 5-alpha position). For a 5 prohormone to convert to an active androgen, in this case, for 5-androstenediol to convert to testosterone, the double bond must isomerize (switch position) to the 4-compound, and an enzyme called 5,4-isomerase brings this about.

However, in the case of 4-androstenediol, no corresponding isomerase reaction is necessary. As a result. the conversion is much more efficient. That means 4-AD "turns" to testosterone much faster and much more efficiently.

I want to be fair to 5-AD, though, and mention that it does have anabolic activity in its unconverted form.5 (The same could be said for 4-AD, but that is beyond the scope of this discussion). That is, 5-AD doesn't seem to require conversion to testosterone to build muscle. It also has the added advantage (or disadvantage, depending on your perspective) of being slightly less androgenic . In other words, 5-AD is less likely to cause side effects, such as hair loss, aggressiveness, and increased libido.

However, when comparing absolute anabolic activity of 4-AD to 5-AD, 4-AD is the clear winner. The only head-to-head study of the two compounds ever published showed 4-AD to be 129% as anabolic as 5-AD.6

Also, you're likely to "feel" the action of 4-AD more than 5-AD when you're at the gym or in the sack because of 4-AD's greater androgenic potency. Anecdotal reports definitely seem to confirm this.

Another downside to 5-AD is its estrogenic activity. Numerous studies have confirmed that, at physiological levels, 5-AD acts as an estrogen agonist.7,8,9,10 In fact, in light of its dual activity as a mild androgen and estrogen, the accepted scientific name for this compound is now "hermaphrodiol" (from the Latin term meaning "of both sexes").

On the other hand, 4-AD has much less estrogenic activity.11 I'm not saying that taking 5-AD will have you in a training bra; in fact, when taken in moderate dosages, most people probably won't notice its estrogenic action. However, I do know one unfortunate person (myself) who experimented with 5-AD at large dosages (1-2 grams a day). This same unfortunate person was trying to fight off a lingering viral infection by taking advantage of 5-AD's immunostimulating action. As a result, this person ended up with a definite, and quite uncomfortable, swelling and tenderness in both nipples.


19-Nor Compounds

The 19-nor family of androgens constitutes a group of compounds that share many of the same properties as their C-19 (andro) counterparts. That is, 19-norandrogens metabolize in an essentially analogous way to C-19.12 In other words, norandrostenedione and 19-nor-4-androstenediol will convert to nortestosterone in the same manner that androstenedione and 4-androstenediol convert to testosterone. 19-nors and C-19s also have anabolic and androgenic activities.

However, the 19-nors have substantially less androgenic activity than the C-19s while maintaining comparable anabolic activity. This does not make 19-nors any better or any worse than C-19s, only different. They are definitely an option for those who want to avoid androgenic effects, such as possible increased head hair loss, increased body hair, increased risk of prostate enlargement, and increased risk of acne.

The low androgenic activity of 19-nors does have its drawbacks, though, the most serious of these being a marked decrease in libido (a common complaint among those who use nandrolone -based steroids as well as 19-nor prohormones).

Another disadvantage of 19-nors is their high cost compared to C-19 prohormones. Also, 19-nors will not give you the heightened focus and CNS psychomotor stimulation that the highly androgenic compounds will. For these reasons, my first recommendation is always for someone to use the C-19 prohormones, and from those I recommend 4-androstenediol because it is by far the most superior.

Now, why does it appear that I'm steering people away from the 19-nor prohormones? Is it for financial reasons? Hardly. Actually, I sell both 4-AD and nor-4-AD and, truth be told, I make more money off the latter.

In my opinion, the use of 19-nors should be confined to women and to those who, for one reason or another, find the risk (albeit slight) of androgenic side effects from prohormones to be unacceptable.


Conclusion

Let me summarize the benefits of the main prohormones:

Androstenedione

• Testosterone Conversion: Moderate
• DHT Metabolite Conversion: Yes
• Estrogen Conversion or Estrogen Agonist: Yes
• Anabolic Properties: Low

4-AD

• Testosterone Conversion: High
• DHT Metabolite Conversion: No
• Estrogen Conversion or Estrogen Agonist: No
• Anabolic Properties: Very high

5-AD

• Testosterone Conversion: Low
• DHT Metabolite Conversion: No
• Estrogen Conversion or Estrogen Agonist: Yes
• Anabolic Properties: High

19-Norandrostenedione

• Nortestosterone Conversion: Moderate
• DHT Metabolite Conversion: No
• Estrogen Conversion or Estrogen Agonist: Yes
• Anabolic Properties: Low

19-NOR-4-Androstenediol

• Nortestosterone Conversion: High
• DHT Metabolite Conversion: No
• Estrogen Conversion or Estrogen Agonist: No
• Anabolic Properties: Very high


Obviously, 4-AD and 19-Nor are, by far, the superior prohormones, and both compare favorably with each other. However, if you're looking for a legal, viable alternative to anabolic steroids —if you want to put on the most muscle in the quickest way possible—4-AD remains the superior choice.

I hope I've helped clear the issue up a little bit. I realize that, in some ways, I might have given you more chemistry than you bargained for, but I hope the intended message still comes through.

T


References

1) 4-androstenediol actually refers to two chemical stereoisomers (stereoisomers are compounds with the same apparent two-dimensional structure but differ in the spatial arrangement of certain atoms in the three dimensional model). The two stereoisomers are 4-androstene-3alpha, 17beta-diol and 4-androstene-3beta, 17beta-diol and they both are naturally occurring and share similar activities. However since commercial androstenediol, although composed of both isomers, contains predominantly the latter isomer (3beta), the discussion of 4-androstenediol usually is confined to this isomer.
2) F. Ungar, M. Gut, and R. Dorfman , J. Biol. Chem., 224, 191-200
3) Shengrong, L. and Parish, EJ., JAOCS, 73, 1435
4) Kundu, N., Sandberg, A.A., and Slaunwhite, W.R., Steroids, 6, 543
5) Ruzicka, Wettstein, Helv. Chim. Acta, 18, 1264
6) Ristovic L.J., Cobanovic M., Kem Ind, 24(7), 389-92
7) Hackenburg R, Turgetto I, Filmer A, J Steroid Biochem Mol Biol, 46(5), 597-603
8) Adams JB, Seymour-Munn K, J Steroid Biochem Mol Biol, 43(6), 499-505
9) Leroy B, Maquaire E, Samperez S, Jouan P, J. Steroid Biochem Mol Biol, 31(4A), 453-8
10) Seymour-Munn K, Adams JB, Endocrinology, 112, 486-491
11) Poortman J, Mol Cell Endocrin, 8(1), 27-33
12) Engel LL, Alexander J, Wheeler M, J Biol Chem, 231, 159-65

[Pinch]

by experience: prohormones are junk