A prohormone is a substance that is a precursor to a hormone, usually having minimal hormonal effect by itself. The term has been used in medical science since the middle of the 20th century. Examples of natural, human prohormones include proinsulin and pro-opiomelanocortin.

For peptide hormones, the conversion process from prohormone to hormone typically occurs after export to the endoplasmic reticulum and often requires multiple processing enzymes. For example, proinsulin is processed by PC 1/2, PC 3, and carboxypeptidase E to afford insulin.Fact|date=January 2007 Proamylin, which is cosecreted with proinsulin, requires the above three factors and an amidating monoxygenase.

For small molecule hormones, the conversion is often one step, and is often used to regulate hormone levels.

Prohormones of anabolic steroids

In the last two decades, prohormones have also been used by bodybuilders, athletes, and nonmedical users of anabolic steroids and other hormones to refer to substances that are expected to convert to active hormones in the body. The intent is to provide the putative benefits of taking an anabolic steroid without the legal risks, and to achieve the hoped-for benefits or advantages without use of anabolic steroids themselves. However, since prohormones are now listed alongside anabolic steroids themselves, they are classified as illegal and subject to the much tighter regulatory requirements of the Food and Drug Administration (FDA) which apply to prescription hormones. The FDA moved to halt sales of androstenedione, a dietary supplement marketed as a muscle enhancer that officials said can stunt growth in children's penises and cause problematic sexual changes in adults. "This is a critical part of the FDA's broad crackdown on unsafe dietary supplements," said Dr. Mark McClellan, the FDA commissioner, at a news conference. "While andro products may seem to have short-term benefits, the science shows that these same properties create real and significant health risks." [ [ Supplement sales banned. Long-term health risks of 'andro' cited by FDA] ]

A typical prohormone is intended to be a precursor of an anabolic steroid like testosterone, which is taken in order to boost the body’s available hormone supply. These precursors are intended to be converted to full, active hormones via an enzymatic process that occurs during metabolism, typically resulting in the addition of whichever atoms happen to be missing from the chemical structure of the compound.

Prohormones are used mainly by athletes looking to increase size, strength, endurance, reduce recovery time or add lean body mass. They are most often used for increasing muscle mass or reducing body fat levels. Life extension groups are also increasingly using prohormones as a means of hormone replacement therapy, as an alternative to prescription drug use.

The use of prohormones has become popular among bodybuilders, since the effects can be similar (though normally much less drastic) to those achieved through the use of synthetic anabolic steroids, including gains in muscular strength and hypertrophy. There are currently many companies manufacturing prohormone products for this purpose.

Prohormones have the same side effects as anabolic steroids, and are dependent upon the user as to which side effects one might experience. Some side effects are acne, hair loss, breast tissue enlargement, and prostate swelling.

The potential for these side effects does exist, but it can be reduced if one uses proper precautionary measures such as post cycle therapy (PCT) Fact|date=April 2008. Generally, if a person is genetically predisposed to a side effect it will occur (i.e.: if someone has a history of male pattern baldness in the family, it could be assumed that this could be a side effect experienced if prohormones are used)

Prohormones are legally sold in most parts of the world and were classified in the United States by the FDA as dietary supplementsFact|date=January 2007 because they consist of compounds that occur naturally in the human body; however their use remains quite controversial and side effects are not uncommon. To date, prohormone products have not been banned in the United States, however, most have not been thoroughly studied, and the health effects of prolonged use are mostly unknown.Fact|date=January 2007

On October 22nd, 2004, President Bush signed into law the Anabolic Steroid Control Act of 2004 (118 Stat. 1661). cite web|url= |title=Public Law 108-358-Oct. 22, 2004 |accessdate=2007-07-08 |date=2004-10-22 |format=PDF |work=108th US Congress ] The bill was written to become effective in 90 days, which was January 20, 2005. This legislation places both anabolic steroids and prohormones on a list of controlled substances (a new type of "regulatory control").Fact|date=January 2007

Common types of prohormones on the market

* "4-androstenedione"
** Converts to: testosterone
** Characteristics:
*** Research indicates a conversion rate of about 5.9%, which means that of the amount taken orally, 5.6% is converted to testosterone.
*** Relatively high rate of aromatization to estrogens, and consequently higher risk of side-effects such as gynecomastia brought on by excessive estrogen formation.
*** Exhibits significant androgenic properties, which may result in side effects such as male pattern baldness, acne, and enlarged prostate. Fact|date=April 2008
* "4-androstenediol (4-AD)"
** Converts to: testosterone
** Characteristics:
*** Conversion rate of about 15.76%, almost triple that of androstenedione, due to utilization of a different enzymatic pathway.
*** No direct conversion to estrogen, though some secondary aromatization does occur through metabolism.
*** Appears to be less androgenic than its cousin, since it does not metabolize into the potent androgen dihydrotestosterone (DHT). Fact|date=April 2008
* "19-norandrostenedione"
** Converts to: nortestosterone (also called nandrolone)
** Characteristics:
*** Only slightly less anabolic than testosterone.
*** Low rate of aromatization to estrogens.
*** Low occurrence of androgenic side effects. Fact|date=April 2008
* "19-norandrostenediol"
** Converts to: nortestosterone
** Characteristics:
*** Same as -dione, except (as with the andros), the conversion rate is higher. Fact|date=April 2008
* "1-androstenediol (1-AD)"
** Converts to: 1-testosterone, a 5-alpha reduced steroid reported to be 700% more anabolic and 200% more androgenic than testosterone; 1-testosterone is better (although rarely) described as dihydroboldenone, the 5-alpha reduced version of the veterinary steroid boldenone Fact|date=April 2008
** Characteristics:
*** Very high conversion rate, because the liver serves primarily to "activate" the compound as it passes through rather than to break it down and excrete it, as is the case with other prohormones.
*** Cannot aromatize to estrogen either directly or through any of its metabolic products. However, 1-Testosterone, being a 5-alpha reduced steroid, is highly androgenic; it is very similar to Dihydrotestosterone (DHT). Many side effects associated with excessive levels of DHT, including male pattern baldness, testicular shrinkage, benign prostate hypertrophy and acne can occur with 1-AD usage. (Journal of Organic chem. vol, 27 1962 iss.1)
*** As with other -diols, 1-AD cannot convert directly to estrogen Fact|date=April 2008.
* "1,4-androstadienedione (1,4 AD)"
** Converts to: boldenone
** Characteristics:
*** High level of oral bioavailability.
*** Low rate of aromatization to estrogens (approximately half that of testosterone).
*** Low occurrence of androgenic side effects. Fact|date=April 2008


External links

* [ Information on Steroid Control Act and Ban on Pro-Hormones]

* Lang, R. [ Pro-Hormones]
* [ General faq about Prohormones]

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