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. 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 or medical risks, and to achieve the hoped-for benefits or advantages without use of anabolic steroids themselves. Since prohormones are not anabolic steroids themselves, they are legally classified as dietary supplements and not subject to the much tighter regulatory requirements of the Food and Drug Administration (FDA) which apply to prescription hormones.
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.
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 are legally sold in most parts of the world and were classified in the United States by the FDA as dietary supplements 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 been banned in the United States, however, most have not been thoroughly studied, and the health effects of prolonged use are mostly unknown.
On October 22nd, 2004, President Bush signed into law the Anabolic Steroid Control Act of 2004 (118 Stat. 1661).  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").
Common types of prohormones on the market
- Converts to: testosterone
- 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 estrogen, 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.
- 4-androstenediol (4-AD)
- Converts to: testosterone
- 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).
- Converts to: nortestosterone (also called nandrolone)
- Only slightly less anabolic than testosterone.
- Low rate of aromatization to estrogen.
- Low occurrence of androgenic side effects.
- Converts to: nortestosterone
- Same as -dione, except (as with the andros), the conversion rate is higher.
- 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
- 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.
- "Public Law 108-358-Oct. 22, 2004" (PDF). 108th US Congress. 2004-10-22. Retrieved 2007-07-08.
- Lang, R. Pro-Hormones