A
prohormone is a substance that is a precursor to a
hormoneA hormone is a chemical released by one or more cells that affects cells in other parts of the organism. Only a small amount of hormone is required to alter cell metabolism. It is essentially a chemical messenger that transports a signal from one cell to another. All multicellular organisms...
, 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
proinsulinProinsulin is the prohormone precursor to insulin made in the beta cell of the islets of Langerhans. In humans, proinsulin is encoded by the INS gene.- Synthesis and post-translational modification :...
and pro-opiomelanocortin.
For peptide hormones, the conversion process from prohormone to hormone typically occurs after export to the
endoplasmic reticulumThe endoplasmic reticulum is an eukaryotic organelle that forms an interconnected network of tubules, vesicles, and cisternae within cells. The lacey membranes of the endoplasmic reticulum were first seen by Keith R. Porter, Albert Claude, and Ernest F...
and often requires multiple processing enzymes.
A
prohormone is a substance that is a precursor to a
hormoneA hormone is a chemical released by one or more cells that affects cells in other parts of the organism. Only a small amount of hormone is required to alter cell metabolism. It is essentially a chemical messenger that transports a signal from one cell to another. All multicellular organisms...
, 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
proinsulinProinsulin is the prohormone precursor to insulin made in the beta cell of the islets of Langerhans. In humans, proinsulin is encoded by the INS gene.- Synthesis and post-translational modification :...
and pro-opiomelanocortin.
For peptide hormones, the conversion process from prohormone to hormone typically occurs after export to the
endoplasmic reticulumThe endoplasmic reticulum is an eukaryotic organelle that forms an interconnected network of tubules, vesicles, and cisternae within cells. The lacey membranes of the endoplasmic reticulum were first seen by Keith R. Porter, Albert Claude, and Ernest F...
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 risks, and to achieve the hoped-for benefits or advantages without use of anabolic steroids themselves. However, in USA, 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 AdministrationThe Food and Drug Administration is a Government agency of the United States Department of Health and Human Services and is responsible for regulating and supervising the safety of foods, tobacco products, dietary supplements, Medication drugs, vaccines, Biopharmaceutical, blood transfusion,...
(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".
A typical prohormone is intended to be a precursor of an
anabolic steroidAnabolic steroids, or anabolic-androgenic steroids , are a class of steroid hormones related to the hormone testosterone. They increase protein synthesis within cells, which results in the buildup of cellular tissue , especially in muscles...
like
testosteroneTestosterone is a steroid hormone from the androgen group. In mammals, testosterone is primarily secreted in the testes of males and the ovaries of females, although small amounts are also secreted by the adrenal glands. It is the principal male sex hormone and an anabolic steroid.In men,...
, 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
enzymaticEnzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process are called substrates, and the enzyme converts them into different molecules, called the products. Almost all processes in a biological cell need enzymes to occur at...
process that occurs during
metabolismMetabolism is the set of chemical reactions that occur in living organisms to maintain life. These processes allow organisms to grow and reproduce, maintain their structures, and respond to their environments. Metabolism is usually divided into two categories. Catabolism breaks down organic matter,...
, 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
hypertrophyMuscle hypertrophy is the increase of the size of muscle cells. It differs from muscle hyperplasia, which is the formation of new muscle cells.- Muscular 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). 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)
On October 22, 2004,
President BushGeorge Walker Bush was the 43rd President of the United States from 2001 to 2009 and the 46th Governor of Texas from 1995 to 2000....
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 substanceA controlled substance is generally a drug or chemical whose manufacture, possession, and use are regulated by a government. This may include illegal drugs and prescription medications ....
s (a new type of "regulatory control"). This bans the selling or possessing of all prohormones.
4-androstenedione
- Converts to: testosterone
- Characteristics:
- Research indicates a conversion rate of about 5.9%, which means that of the amount taken orally, 5.9% is converted to testosterone.
- Relatively high rate of aromatization to estrogen
Estrogens are a group of steroid compounds, named for their importance in the estrous cycle, and functioning as the primary female sex hormone, their name comes from estrus/oistros + gen/gonos = to generate.Estrogens are used as part of some oral contraceptives, in estrogen replacement...
s, and consequently higher risk of side-effects such as gynecomastiaGynecomastia, , is the development of abnormally large mammary glands in males resulting in breast enlargement. The term comes from the Greek γυνή gyne meaning "woman" and μαστός mastos meaning "breast"...
brought on by excessive estrogen formation.
- Exhibits significant androgen
Androgen is the generic term for any natural or synthetic compound, usually a steroid hormone, that stimulates or controls the development and maintenance of masculine characteristics in vertebrates by binding to androgen receptors. This includes the activity of the accessory male sex organs and...
ic properties, which may result in side effects such as male pattern baldness, acneAcne vulgaris is a common skin condition, caused by changes in pilosebaceous units, skin structures consisting of a hair follicle and its associated sebaceous gland, via androgen stimulation. It is characterized by noninflammatory follicular papules or comedones and by inflammatory papules,...
, and enlarged prostateThe prostate is a compound tubuloalveolar exocrine gland of the male mammalian reproductive system. Females do not have prostate glands...
.
4-androstenediol4-Androstenediol is an androstenediol that is converted to testosterone. The conversion rate is about 15.76%, almost triple that of androstenedione, due to utilization of a different enzymatic pathway. There is no direct conversion to estrogen, though some secondary aromatization does occur...
(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).
19-norandrostenedione19-Norandrostenedione is a precursor of the anabolic steroid nandrolone. Until 2005 19-Norandrostenedione was available without prescription in United States, where it was marketed as a prohormone, but it is now classified as a Schedule III drug...
- 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.
19-norandrostenediol
- Converts to: nortestosterone
- Characteristics:
- 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
5-Alpha reductase is an enzyme involved in steroid metabolism.-Function:It converts testosterone, the male sex hormone, into the more potent dihydrotestosterone:Note the major difference — the Δ4,5 double-bond on the A ring...
version of the veterinary steroid boldenone
- 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.
1,4-androstadienedione (1,4 AD)
- Converts to: boldenone
Boldenone , also known under the trade names Equipoise, Ganabol, Equigan and Ultragan, is an anabolic steroid developed for veterinary use, mostly for treatment of horses...
- Characteristics:
- High level of oral bioavailability.
- Low rate of aromatization to estrogens (approximately half that of testosterone).
- Low occurrence of androgenic side effects.
Methyl 1-testosterone (M1-T)
- Characteristics:
- similar to testosterone except instead of a 4,5-double bond it has a 1,2-double bond.
- has about 20% oral bioavailability compared with less than 5% for testosterone
- non-aromatizing to estrogen or DHT
- has irritative properties making it too painful to inject, and has extremely bitter taste, making transcutaneous topical solutions the only practical human delivery method. It was commercialized this way in the United States before 2005, when it became illegal together will all other prohormones.
- History: 1-T was discovered in the 1950s, explored as a potential anabolic product by the pharmaceutical company G.D. Searle, but not commercialized at the time due to difficulty in delivery.
- Also considered a steroid
Prohormones today
A number of new Prohormones have been introduced in the past few years due to advances by supplement manufacturers. They include the following:
-
- 17b-methoxytrienosterone
- M-1,4ADD (17a-methyl-1,4-androstadiene-3,17diol)
- andrenosterone, 11-oxo-androstenedione
- 12-ethyl-3-methoxy-gona-diene
- 17b-Methoxy-Trienbolone
- 2-androstenol acetate
These compounds all have differing characteristics, varying significantly between those that are androgenic (masculinizing) and those which have estrogenic effects when ingested in the body.