Fear of Freedom, Nature and The Right To Possess (Big) Arms

Of late I have had a lot of questions from readers, HRT physicians and industry manufacturers concerning the safety and nature of prohormones and the newer so-called prosteroids. In one case, a concerned hard-core AAS user stated his happiness at the soon to be illegal status of the prohormone and prosteroid industry, while a few others question the lack of long-term studies to validate the effects, both good and bad, of these OTC supplements.

Just Pointing Out The Obvious Facts…

Let’s begin by pointing out that there are already too many countries which have opted to totally remove the capacity for freedom of choice…but have relatively open boarders. Please feel free to travel there often if this is a preferred environ. Just pointing out what should be obvious to any thinking individual, no offense meant.

*Choosing tonotact on ones freedom of choice is always an individual’s option. No restrictive legislation required.

*Removing the rest of the country’s ability to have either option is not necessary for you to opt out. You already have that ability without a new law.

What Are Prohormones and Prosteroids?

Technically speaking, a prohormone is a hormone-like substance that has little or no potential for activity in an unconverted or non-chemically altered state. As example is the now illegal prohormone androstenedione (More choices gone). This is a naturally occurring adrenal hormone also produced be other tissues including the testes (at least in males that is. Women do not have testes…which is another obvious fact, or at least should be).

The body uses androstenedione as a precursor to produce other hormones such as androstenediols, testosterone and estrogens. Depending upon the dominant enzyme(s) present in the tissue or circulatory system at that time, various amounts of one or many of these hormones are produced when androstenedione is present. The amount of androstenedione present can also alter the amounts and ratios as well. As a rule the environ created by high dose androstenedione utilization is better for growing breasts than muscle for males, but oddly reversed for females.

The term prosteroid seems to have been coined by the supplement industry though it is actually accurate. A prosteroid is a legal (so far) hormone possessing significant activity in its current unaltered state. Some good examples of prosteroids are 1-Testosterone or (AKA 1-Test), 4-Hydroxytestosterone (AKA Testosterone-OH), 4-Hydroxyandrostenedione (AKA Formestane), 4-Hydroxynandrolone (AKA Nandrolone-OH) and the various esters and alkylations there of. These seem to be the prosteroids of greatest question, though they certainly are not new.

The Studies and Testing Began…At the Dawn Of Man

What many are unaware of is that most of these 4-Hydroxyandrogens are naturally occurring in the body and have been (in varying ratios) since the dawn of man (and women). Basically, I would have to say that long-term testing (several thousand years…give or take a millennium or two) has been reasonably validated and their affects upon the body to be less likely death oriented due to the continuance of our existence. (But those whom are waiting for longer studies can opt to merely become eunuchs until further results are in)

Warning: Science Geek Stuff

4-HydroxyTestosterone (4,17-beta-dihydroxy-4-androstene-3-one) is a metabolite or derivative of the naturally occurring precursor hormone 4-Hydroxy-4-Androstenedione. Huh? (You asked for it!)

Androgen Conversion and Metabolism

As many already know, the biosynthesis and metabolism of steroid hormones in the ovaries, testes and adrenals begins with the endogenous manufacturing of cholesterol. Cholesterol is then metabolized to pregnenolone which is next metabolized to 17-HydroxyPregnenolone for the creation of Dehydroepiandrosterone(DHEA). (With me so far?) DHEA is then converted to Androstenedione. Once created, androstenedione can then continue to several different Carbon hydroxylations such as estrone, testosterone, and androstanes. Hmmm. Okay…

Since our interest here is more specific, I will only make you suffer through the metabolism of androstenedione in regards to C4 hydroxylation for the natural in body production of4-Hydroxyandrostenedione (AKA Formestane) and 4-Hydroxytestosterone (AKA Testosterone-OH).

4-Hydroxytestosterone and 4-Hydroxyandrostenedione occur as a result of the effects of specific enzymes upon androstenedione. (See Figure Below) As explained earlier, androstenedione is naturally produced in humans and animals. Androstenedione hydroxylation is also known to occur at C6B, C11B, C15A, C16A, C16B, and at C19. Though steroid hydroxylation at C4 occurs in nature. Since Androstenedione and 4-Hydroxyandrostenedione productions occur naturally, then metabolites of these compounds are naturally occurring.

Although the research also suggests that since steroid hydroxylation at C4 occurs in nature, it should be noted that there should be another direct pathway for this compound. (17beta-hydroxy-4-androstene-3-one to 4,17beta-dihydroxy-4-androstene-3-one).

Human Biosynthesis Pathways for 4-Hydroxyandrogens

4-Androstene-3,17-dione (Androstenedione)

:

(4-Hydroxylation by) EXP2G1

:

4-Hydroxy-4-androstene-3,17-dione (4-Hydroxyandrostenedione/Formestane)

:

17BHSD

:

4,17-Dihydroxy-4-androstene-3-one (4-Hydroxytestosterone/Testosterone-OH)

*It should be noted that since all nandrolones are progesterone derivatives (and progesterone is naturally occurring as well) the metabolism and creation of 4-Hydroxynandrolone (Nandrolone-OH) follows a similar pathway.

Searle Thought About It…

Several years ago, the pharmaceutical giant Searle studied the possibility of the inclusion of Testosterone-OH, Nandrolone-OH and various alkylated variants for medical required AAS (Anabolic-Androgenic-Steroid) applications but dropped the research. The reason was politically motivated as it was during the last era of “anything that positively affects musculature or being male is evil”. Naturally, during such a negative environment, the sales potential are greatly diminished. (Odd that a Bush ran the country then too) However, 4-Hydroxyandrostenedione has been available under the generic name of Formestane and trade name of Lentaron I.M. Depot in many countries for many years…since Testosterone-OH is one of the natural metabolites…

Are Prosteroids Effective?

Most will recall the rush to use DHEA and androstenedione products during the big EAS era (“cause they have effects just like steroids…Geez!) with bitter memories of muscle loss, gyno and increased fat deposits in a rather feminine manner. The problem was that these wereprohormones requiring a very specific physiological environ to render any minute degree of anabolic muscle building effect.

Many of the currentprosteroids are as anabolic or more so than some synthetic AAS. Why? Because theyare AAS, in many cases, simply not yet classified as such. (Though 3 states have already included many in theirControlled Substance Acts as AAS). In the case of hydroxyandrogens the safety profile is greatly improved due to a lack of estrogen conversion or reduction to DHT or its derivatives. Of course properly structure protocols and recovery phase are still a must for obvious reasons.

So what have we learned?

1. Anyone can already abandon choice and have others think for them. (No change in laws required)
2. Most of the current effective and popular prosteroids originate in humans naturally, thus VERY LONG term in vivo testing has occurred.
3. There is long-term scientific research available as well. (See end of article)
4. That some prefer being eunuchs to being unique…which is fine with me.

Personally I really do not care if someone employs prohormones, prosteroids or even AAS in there training protocols. Like food, water and everything else in life, it is just chemistry. But I do believe that individuals should retain their right to think and chooseSecond generation aromatase inhibitor--4-hydroxyandrostenedioneBREAST CANCER RESEARCH AND TREATMENT , 30(1):81-87 1994

Other Available Research

Gardi R et al. New classes of orally active hormonal derivatives. II. 17-Cycloalk-1\'-enyl ethers of 17 -hydroxy-androstanes and 19-norandrostanes. Steroids. 1972 May;19(5):639-47.

Second generation aromatase inhibitor--4-hydroxyandrostenedione BREAST CANCER RESEARCH AND TREATMENT , 30(1):81-87 1994

LACK OF EVIDENCE FOR AROMATASE IN HUMAN PROSTATIC TISSUES EFFECTS OF 4-HYDROXYANDROSTENEDIONE AND OTHER INHIBITORS ON ANDROGEN METABOLISM CANCER RESEARCH , 49(23):6551-6555 1989

DOSE-RELATED ENDOCRINE EFFECTS AND PHARMACOKINETICS OF ORAL AND INTRAMUSCULAR 4 HYDROXYANDROSTENEDIONE IN POSTMENOPAUSAL BREAST CANCER PATIENTS CANCER RESEARCH , 49(5):1306-1312 1989

Effects of 4-hydroxyandrost-4-ene-3,17-dione and its metabolites on 5 alpha-reductase activity and the
androgen receptor. J Enzyme Inhib 1992;6(2):141-7

Poon GK, et al. Investigation of conjugated metabolites of 4-hydroxyandrost-4-ene-3,17-dione in patient urine by liquid chromatography-atmospheric pressure ionization mass spectrometry. Drug Metab Dispos. 1992 Nov-Dec;20(6):941-7.

Davies JH et al. Effects of 4-hydroxyandrost-4-ene-3,17-dione and its metabolites on 5 alpha-reductase activity and the androgen receptor. J Enzyme Inhib. 1992;6(2):141-7.

Vitali R et al. New classes of orally active hormonal derivatives. 1. Alkyl androstan-17beta-YL and alkyl 19-norandrostan-17beta-YL mixed acetales. Steroids 1966 Oct 8:4 527-36

Addendum?

Naturally there will always be someone reading this article assuming that I own a company that sells these products. No, I am one of the founders ofAGR Nutrition. We do not sell any prohormones or prosteroids. We do offer some other very effective supplements, of course.

My consultation firm has done prototype and production designs for a few companies like H.M. Gear. We are paid a flat one-time fee for designs and production set up (the companies have to agree to our terms…we control the product from inception to production to assure quality) so I really do not care if anyone buys their products by the case or not. However, if you have read either of my current books (Chemical Muscle Enhancement and Building the Perfect Beast) then you already realize my interest is in lab research, writing and building beasts.

Author L. Rea