Vol. 2, #4
January 22, 2005

Q: What are prohormones and what are they good for? - Layperson

A: Prohormones are steroid hormones, which is not to say that prohormones are steroids. It is simply the scientific term for any hormonal substance manufactured in the body from cholesterol (this includes testosterone and estrogen, but also Vitamin D and others) and above all exogenous hormonal substances. In a way they are comparable to steroids, and though minor and at much less risk, similar side effects can occur. If you are still growing, pregnant or are succeptible to the effects of estrogen and dehydro-testosterone (DHT) formation, it's wise to stay away from prohormones.

Prohormones need enzymes to convert to a target hormone, which is responsible for most of the anabolic effects. Because this requires naturally occurring enzymes the amount that is converted is limited, and therefore so are the results from taking it. With drugs, such as steroids, the effects are dose-dependent - the more you take, the more you gain. Introducing an exogenous steroid hormone into the body will initially, through a mechanism called negative feedback, stop the natural production of the hormone testosterone. Negative feedback is a loop mechanism. Testosterone is secreted by the hypothalamus which releases Gondatropin releasing hormone (GhRH) which stimulates the release of Luteinizing hormone (LH or Gonadotropin) from the anterior pituitary. In the testes LH will signal the manufacture of Dehydro-epiandrosterone (DHEA) from cholesterol in the Leydig Cells. DHEA converts to androstenedione and eventually testosterone. When the need for testosterone is satisfied the testosterone will signal the hypothalamus and secretion is stopped. Introducing these substances directly will give that same signal that stops production. Because the manufacture of DHEA in the gonads is halted and they fall into disuse. This causes testicle shrinkage and in the long run can be responsible for infertility, loss of libido and even impotence. This problem is addressed by the term cycling. By going on a hormone for a while and then staying off of it for a similar or longer period, we give natural production a chance to recover. Minor shrinkage can take place but should disappear after a few weeks of disuse. This brings with it a few conclusions:

A. The product should always be cycled, prolonged or continued use may cause more lasting damage. 8-10 weeks is the longest a stack should be. Even that may be pushing it.

B. The time you are off the supplement should be adequate, at least as long but preferably longer than the amount of time you were on it. If this rule is not observed, the testes may not get a chance to recover adequately and the cumulative effect of two close cycles may result in similar problems.

Estrogen-Related Issues

Estrogen is a common denominator for a group of hormones with feminizing characteristics that are obviously more active in the female of our species. Estradiol and consequently estrone are the strongest and most relevant. There are a great deal that are biologically not active enough to be of concern. In the body, when the hormones are converted, a great deal of them (the amount depending on the prohormone used) can actually start producing estrogen. Even if this is not the case, the target hormone, testosterone especially, can undergo a process called aromatisation in which the testosterone molecule is transformed into an estrone molecule. This happens at the 3rd carbon position (most anabolic steroid hormones have 17 carbons) where an A-ring is formed.

Males may experience the consequences of feminizing effects. Estrogen has a very retentive effect on water. This means that large amounts of water can be stored, making you bigger but not with muscle, when using them. Most of this weight disappears when estrogen:testosterone levels return to normal. In itself this retention is moderately anabolic and not so bad at all, if it didn't go at the expense of the amount of testosterone. It also increases the chances of adipose (fat) storage throughout the body (women have a naturally higher BF percentage than men). But as stated, they don't have to be bad necessarily, they may even aid the results. Of more concern is gynocomastia (gyno) , commonly referred to as "bitch tits", which indicates the formation of breast tissue in men as a result of estrogens. This can be caused by alcohol or high body-fat as well, so keep in mind that these conditions will influence your risk of gyno. The risk of severe gyno from taking a prohormone is low. Most likely that would take a dose that offers no additional effects, of a product that readily makes the conversion, such as andro or 5-diol. What does regularly happen is that someone gets itchy nipples and they get a bit puffy. These are common symptoms and will disappear. Itching is no real indicator, but if they get puffy it may be a source of concern. If you are doing an 8-week stack and in the 5th or 6th week you see some swelling, continuing is not such an incredible risk. The effect is mostly reversible and should disappear after three weeks of disuse. If you get it full blown the first week or so, don't hesitate, just quit. It would be unwise to continue if you are obviously so succeptible. The risk of it being permanent becomes larger too, and if gyno should occur the only way to remove it is surgically.

Androgen-Related Issues

An androgen is any substance that creates male-specific characteristics in the body, masculinizing effects if you will. You'd think this would be a positive thing, and mostly it is, apart from a few things. For the most part androgen related issues are the result of dehydro-testosterone (DHT) formation. FSH (follicle stimulating hormone, the other sex-hormone secreted under influence of GnRH) signals the Sertoli cells which transform the molecule to DHT. DHT is responsible for sperm maturation and most masculine characteristics-increased body-hair, deeper voice, and increased sex-drive. What should be of concern is that like all fat-soluble products (and testosterone is made of cholesterol) it stores in the skin, and DHT seems to have an affinity for the scalp, which may cause hair loss on the top of the scalp.

In real terms, it all depends, yet again, on how you personally react to it. Some people take mega-doses and don't lose anything, others may notice extra hairs clogging the drains after a mere three weeks. Generally, if there is a history of male-pattern baldness on your mother's side of the family (the condition is hereditary in matri-linear fashion) it's best to be on your guard and discontinue use of the product immediately at the first sign of excessive hair loss. Hair loss is almost always irreversible. It may be wise to make the majority of your intake a low-androgenic compound.

Other side-effects as a result of androgenic substances include acne, which is the most common side-effect of prohormones, but it is very temporary, this should clear up within the odd week or two after discontinuing the product. Often times it will be limited to a few zits here and there. For older people there is the risk of prostate enlargment. In heavy androgenic steroids this can even greatly increase the risk of prostate cancer. One sign of prostate enlargment is overurination. The use of blocking substances, such as chrysin, or, in this case for the older bodybuilder most at risk (50 to 69 especially is the target group), saw palmetto is advisable.

Common types of prohormones on the market

  • 4-androstenedione
    • Converts to: testosterone
    • Characteristics:
      • Research indicates a conversion rate of about 5.6%, 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
    • 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-norandrostenedione
    • Converts to: nortestosterone (also called nandrolone)
    • Characteristics:
      • Only slightly less anabolic than testosterone.
      • Low rate of aromatization to estrogen.
      • 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.k.a 1-Dihydrotestosterone, 1-DHT (a 5-alpha reduced form of testosterone reported to be 700% more anabolic and 200% more andronergic)
    • Characteristics:
      • Very high conversion rate, owing to the fact that 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 is highly andronergic being a Dihydrotestosterone derivative. Many side effects associated with excessive levels of DHT, including male pattern baldness, testicular shrinkage, benign prostate hypertrophy and acne can occure with 1-AD usage. (Journal of Organic chem. vol, 27 1962 iss.1)
      • As with other -diols, .

On October 22nd, 2004, President Bush signed into law the Anabolic Steroid Control Act of 2004. Many steroid precursors will soon become controlled substances. The prohormone criminalization legislation (S. 2195) has now been passed by both the Senate and the House. The effective date of the bill will begin to run 90 days from the date the President signs the bill into law. For those of you who are especially interested in an exact date, it would be reasonable to say that the bill could be expected to take effect on or around January 10-20, 2005. This bill, which was introduced by Senators Joseph Biden (D-Del.) and Orrin Hatch (R-Utah), provided for the listing of steroid hormone precursors such as androstenedione ("andro") under the Controlled Substances Act. Such action effectively prohibits the marketing of these substances as dietary supplements by regulating them as Schedule III controlled substances. The U.S. Anti-Doping Agency (USADA) has called steroid precursors "the functional equivalent of steroids."

The legislation adds 18 substances to the list of banned anabolic steroids. Here is the list of banned items:

  1. androstanediol-- 
    1. 3b,17b-dihydroxy-5a-androstane; and 
    2. 3a,17b-dihydroxy-5a-androstane; 
  2. androstanedione (5a-androstan-3,17-dione); 
  3. androstenediol-- 
    1. 1-androstenediol (3b,17b-dihydroxy-5a-androst-1-ene); 
    2. 1-androstenediol (3a,17b-dihydroxy-5a-androst-1-ene); 
    3. 4-androstenediol (3b,17b-dihydroxy-androst-4-ene); and 
    4. 5-androstenediol (3b,17b-dihydroxy-androst-5-ene); 
  4. androstenedione-- 
    1. 1-androstenedione ([5a]-androst-1-en-3,17-dione); 
    2. 4-androstenedione (androst-4-en-3,17-dione); and 
    3. 5-androstenedione (androst-5-en-3,17-dione); 
  5. bolasterone (7a,17a-dimethyl-17b-hydroxyandrost-4-en-3-one); 
  6. boldenone (17b-hydroxyandrost-1,4,-diene-3-one); 
  7. calusterone (7b,17a-dimethyl-17b-hydroxyandrost-4-en-3-one); 
  8. clostebol (4-chloro-17b-hydroxyandrost-4-en-3-one); 
  9. dehydrochloromethyltestosterone (4-chloro-17b-hydroxy-17a-methyl-androst-1,4-dien-3-one); 
  10. 1-dihydrotestosterone (a.k.a. `1-testosterone') (17b-hydroxy-5a-androst-1-en-3-one); 
  11. 4-dihydrotestosterone (17b-hydroxy-androstan-3-one); 
  12. drostanolone (17b-hydroxy-2a-methyl-5a-androstan-3-one); 
  13. ethylestrenol (17a-ethyl-17b-hydroxyestr-4-ene); 
  14. fluoxymesterone (9-fluoro-17a-methyl-11b,17b-dihydroxyandrost-4-en-3-one); 
  15. formebolone (2-formyl-17a-methyl-11a,17b-dihydroxyandrost-1,4-dien-3-one); 
  16. furazabol (17a-methyl-17b-hydroxyandrostano[2,3-c]-furazan); 
  17. 13a-ethyl-17a-hydroxygon-4-en-3-one; 
  18. 4-hydroxytestosterone (4,17b-dihydroxy-androst-4-en-3-one); 
  19. 4-hydroxy-19-nortestosterone (4,17b-dihydroxy-estr-4-en-3-one); 
  20. mestanolone (17a-methyl-17b-hydroxy-5a-androstan-3-one); 
  21. mesterolone (1a-methyl-17b-hydroxy-[5a]-androstan-3-one); 
  22. methandienone (17a-methyl-17b-hydroxyandrost-1,4-dien-3-one); 
  23. methandriol (17a-methyl-3b,17b-dihydroxyandrost-5-ene); 
  24. methenolone (1-methyl-17b-hydroxy-5a-androst-1-en-3-one); 
  25. methyltestosterone (17a-methyl-17b-hydroxyandrost-4-en-3-one); 
  26. mibolerone (7a,17a-dimethyl-17b-hydroxyestr-4-en-3-one); 
  27. 17a-methyl-*1-dihydrotestosterone (17b-hydroxy-17a-methyl-5a-androst-1-en-3-one) (a.k.a. `17-a-methyl-1-testosterone'); 
  28. nandrolone (17b-hydroxyestr-4-en-3-one); 
  29. norandrostenediol-- 
    1. 19-nor-4-androstenediol (3b, 17b-dihydroxyestr-4-ene); 
    2. 19-nor-4-androstenediol (3a, 17b-dihydroxyestr-4-ene); 
    3. 19-nor-5-androstenediol (3b, 17b-dihydroxyestr-5-ene); and 
    4. 19-nor-5-androstenediol (3a, 17b-dihydroxyestr-5-ene); 
  30. norandrostenedione-- 
    1. 19-nor-4-androstenedione (estr-4-en-3,17-dione); and 
    2. 19-nor-5-androstenedione (estr-5-en-3,17-dione; 
  31. norbolethone (13b,17a-diethyl-17b-hydroxygon-4-en-3-one); 
  32. norclostebol (4-chloro-17b-hydroxyestr-4-en-3-one); 
  33. norethandrolone (17a-ethyl-17b-hydroxyestr-4-en-3-one); 
  34. oxandrolone (17a-methyl-17b-hydroxy-2-oxa-[5a]-androstan-3-one); 
  35. oxymesterone (17a-methyl-4,17b-dihydroxyandrost-4-en-3-one); 
  36. oxymetholone (17a-methyl-2-hydroxymethylene-17b-hydroxy-[5a]-androstan-3-one); 
  37. stanozolol (17a-methyl-17b-hydroxy-[5a]-androst-2-eno[3,2-c]-pyrazole); 
  38. stenbolone (17b-hydroxy-2-methyl-[5a]-androst-1-en-3-one); 
  39. testolactone (13-hydroxy-3-oxo-13,17-secoandrosta-1,4-dien-17-oic acid lactone); 
  40. testosterone (17b-hydroxyandrost-4-en-3-one); 
  41. tetrahydrogestrinone (13b,17a-diethyl-17b-hydroxygon-4,9,11-trien-3-one); 
  42. trenbolone (17b-hydroxyestr-4,9,11-trien-3-one); and 
  43. any salt, ester, or ether of a drug or substance described in this paragraph   

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DISCLAIMER:  The information in this column, is NOT intended to diagnose and/or treat any health related issues and is provided solely for informational purposes only. Consult the appropriate healthcare professional before making any changes to your healthcare regime. Even what may seem like simple changes in the diet for example, can interact with, and alter, the efficiency of medications and/or the body's response to the medications. Many herbs and supplements exert powerful medicinal effects. Neither the author, nor the website designers, assume any responsibility for the reader's use or misuse of this information.

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