The Hypertrophy and Hormones Debate
By Thomas Rowland


Part 2: Testosterone prohormone supplements
Physiological effects and ethical considerations


In part 1 of ‘The Hypertrophy and Hormones Debate’ we explored how the exercise induced increase in ‘anabolic’ hormones does not likely function to regulate strength or hypertrophy adaptation, and therefore a training programme should not be centred around this concept. The next logical line of inquest would be to ask whether elevating our natural ‘anabolic’ hormone levels through some form of supplementation is effective. Certainly, there is no doubt about the powerful effect of testosterone, anabolic steroids, and other hormones. These are however widely banned substances both in the legal and sporting sense with ethical considerations regarding their use in sport. That, and this is a natural bodybuilding site after all and I think the natural stance on steroids is pretty clear. A topic that somewhat lingers in between the line of ‘acceptable’ supplements and ‘drug’ use however is prohormones. It is the ethical considerations and physiological effects of prohormone supplementation that will be discussed in this article.

What are pro-hormones?

Prohormones are chemicals that can be converted to hormones, many of which are produced naturally by the body. With regards to bodybuilding, the prohormones of interest are testosterone prohormone supplements. The three primary ones are known as dehydroepiandrosterone (DHEA), androstenedione (ASD) and androstenediol (ASDL). We will address the ethical considerations, and the various natural federations stance on prohormones later on. First, the logical questions to ask are 1) does prohormone supplementation increase testosterone levels in humans and 2) does supplementation alongside resistance training actually result in greater increases in strength and hypertrophy? A review by Brown et al (1) was published awhile back that answers these two questions and is summarised below.

Do Prohormones increase testosterone levels?

The theory goes that if prohormones are administered, they will be converted to testosterone within the body, and this greater testosterone level will enhance training adaptation. However, just because these prohormones are capable of being converted to testosterone, it doesn’t necessarily mean they will be converted to testosterone in excess in humans. The prohormones discussed above can also be converted to several other substances, not just testosterone. Table 1 summarises what research shows about the acute and longer-term administration of ASD, ASDL and DHEA in male humans:

Table 1. The acute and longer term effects of prohormones administration in males.

ProhormoneAcute Administration EffectsLonger-term Administration Effects
Androstenedione100-200mg does not increase testosterone levels.

300mg may increase testosterone levels slightly if natural levels are low.
100-300mg does not increase testosterone levels in men but may have an effect in the elderly or diseased who have low resting levels.
Androstenediol200mg does not increase testosterone levels.

Sublingual (under the tongue) administration of 21.4mg may increase testosterone levels.
200mg daily dose does not increase testosterone levels but may increase estradiol levels.
DHEA100mg does not increase testosterone levels.Up to 1600mg does not increase testosterone levels.


As you can see from the table 1, there is some evidence that certain doses of ASD or ASDL might increase testosterone levels in some individuals acutely, but the more important longer-term studies generally show that these three testosterone prohormones are not converted to testosterone in healthy young men (1).

What about the women?

Obviously, when discussing hormones, gender is likely to play an important role due to the different hormonal profiles between men and women. In contrast to men, ingesting 100-300mg of ASD does appear to increase testosterone levels in women although the size of the increase is unclear (1). Estradiol concentration is however also increased at the upper doses of ASD (1). Similarly, doses of 100-400mg of DHEA increase testosterone levels in women, however unlike ASD, with no effect on estrogens (1). It is worth noting that prohormone use in women, like anabolic steroids, is associated with increased symptoms of masculinisation (1).

Does prohormone supplementation enhance training adaptation?

The fact that prohormones are not likely converted to testosterone in most humans seems to already put the nail in the coffin, but lets look at what training studies have been conducted on supplementing resistance training with testosterone prohormones.

  • Androstenedione – In their review of the literature, Brown et al (1) highlight that several studies using doses ranging from 100-300mg in either trained or untrained subjects and of varying age groups, all showed that ASD supplementation does not enhance increases in strength, muscle mass, fiber size or body fat loss in response to resistance training.

  • Androstenediol – At the time of their review, only one study had examined androstenediol intake and resistance training and this again showed that ADSL intake did not enhance training adaptation in any measure (1). To my knowledge, there have still not been any training studies on ASDL published since.

  • DHEA – While a few studies have been conducted on DHEA, the general overview is again that DHEA does not appear to enhance fat loss, strength gain or hypertrophy (1).

    As somewhat expected from the previous section, longer-term training studies fail to show convincing evidence that any of the three prohormones discussed above will enhance a weight lifters training programme.

    There remains to be few, if any, long-term trials conducted in healthy young women. This seems surprising as it would be interesting to investigate considering prohormones do appear to increase testosterone levels in them.

    So all prohormones are absolutely useless right? Well, since the review by Brown et al (1), there hasn’t been much research on prohormone use in athletes. What we can conclude from the above is that at the doses studied, DHEA, ASD and ASDL do not appear to be efficiently converted to testosterone or augment training adaptation in healthy young(ish) men. That is not to say however that at higher doses or with alternative administration routes, these prohormones are not anabolic (1).

    In addition, as discussed further on, although these well known prohormones have now largely been banned in natural federations and even illegal to possess, newer prohormones not yet banned or not yet illegal are coming out and being sold as dietary supplements.

    For example, a recent study investigated supplementing a 4-week resistance training programme with 3ß-hydroxy-5a-androst-1-en-17-one (2). This prohormone is capable of converting to 1-testosterone, which possesses potent anabolic effects stronger than endogenous (naturally produced) testosterone. In this reasonably well designed small trial in trained men, they found some evidence suggesting that supplementing with 150mg of 3ß-hydroxy-5a-androst-1-en-17-one can enhance resistance exercise induced hypertrophy, strength gains and body fat loss. However, supplementation also came with unwanted changes to markers of cardiovascular, liver and possibly kidney health, suggesting potential health consequences with this prohormone. More generally, what this study shows is that without comprehensive study of every prohormone compound out there (which takes a lot of time and a lot of money) it is impossible to say that none possess potent anabolic properties.

    In addition, without going into detail about the Testosterone:Epitestosterone (T:E) ratio, it would be interesting to see prohormone research include this measure. This would give athletes a clear indication about how a prohormone might relate to their drug testing, as many athletes are aware that the T:E ratio is used in doping tests. For example, a fancy new prohormone might be released that isn’t yet banned. An athlete might start using it but it turns out to be highly effective at increasing testosterone levels and the athlete ends up failing a drug test (arguably rightly so) because their T:E ratio is too high. Depending on the federation, either a 4:1 or 6:1 ratio is used as being within an acceptable ‘non-enhanced’ range.

    Ethical Considerations

    We now turn our attention to some of the ethical considerations regarding prohormone supplementation. When prohormones first came on the scene in the late 90s they could legally be sold as dietary supplements in the US. As concern over their safety grew, the FDA changed their definition of anabolic steroids, such that prohormones were now included, thus making them illegal to sell without prescription (1). In the UK, many prohormones have now been classified as class C drugs (3). Despite this, as most bodybuilders are aware, there seems to be an endless number of supplement companies and some list prohormones as ingredients and some might even be contaminated with banned substances (4).

    The majority of this article has argued that based on available evidence, the main prohormones, DHEA, ASD and ASDL, are unlikely to elevate testosterone or enhance training adaptation. However, as mentioned above, prohormones have not been extensively studied, in particular, dose response and alternative administration studies are limited (1). This leaves the possibility then, that at high doses or delivery mechanisms other than oral ingestion, these prohormones might convert to testosterone and enhance training adaptation (1). This brings us to the general debate about the use of drugs in sport, which we will not go into here as a whole book could be written on the topic.

    Nonetheless, given the legal status of most prohormones, and the possibility of them possessing anabolic effects and/or being harmful, it seems wise for them to be banned by natural bodybuilding and powerlifting federations.

    So where do the natural federations stand on prohormone supplementation?

    Given that prohormones are still used as ingredients in some supplements it is important to understand, 1) what is in the supplements you’re taking and 2) what the rules are of the federation you decide to compete in. On the amateur side of the UK bodybuilding scene, all four of the prohormones mentioned in this article are banned by the NPA, BNBF and UKDFBA and have the following policies:

  • NPA - follows WADA guidelines and its policy is that you should never have used prohormones (5).

  • BNBF - states that all hormone precursors are banned but have a 7-year ban limit (6).

  • UKDFBA - follow the WNBFs (their pro affiliate) guidelines, which states that all hormone precursors are banned, again with a 7-year ban limit (7).

    The professional ranks policies are as follows:

  • WNBF - bans all hormone pre-cursors and have a T:E ratio limit of 6:1 (8).

  • DFAC - abides by WADA guidelines, banning all prohormones and have a T:E ratio limit of 4:1 (9).

  • IFPA - states that DHEA, ASD and ASDL are all banned but within their rules it does not explicitly say that all hormone precursors are banned (10). This suggests that other prohormones could be utilised and would only produce a failed drug test if their T:E ratio was above the IFPA 6:1 limit. However, I was informed by the IFPA that prohormones not listed in their drug testing guidelines document may still be banned due to conveying an unfair anabolic advantage, and as such athletes should contact them specifically with the substance in question to find out if it is banned or not.

  • NGA - appears to have the most relaxed stance on prohormones, with the rules stating hormone precursors are not banned, but if used and produce a T:E ratio of greater than 6:1, it will be considered a failed drug test (11).

    In Summary

  • Testosterone prohormones such as DHEA, ASD and ASDL are steroid hormones that are purported to enhance training adaptation by converting to testosterone in the body.

  • There is limited evidence however that in humans DHEA, ASD or ASDL are actually converted into testosterone in healthy young men. They do however lead to increases in testosterone in women.

  • Studies combining resistance training with prohormone supplementation in young healthy men have generally failed to show supplementation enhances any measure of hypertrophy or strength.

  • The possibility still remains however that at high doses not studied or with alternative administration routes, ASDL, ASD or DHEA do possess anabolic properties. It is also possible other prohormones out there not studied possess anabolic effects.

  • While there are subtle differences, most prohormones are banned by the majority of natural bodybuilding federations, except the NGA.

  • Prohormones are however still found in some supplements so natural competitors should make sure they closely check the ingredients and reliability of supplements and the rules of the federation they choose to compete in.

    References:

    (1) Brown GA, Vukovich M and King D. Testosterone Prohormone Supplements. Medicine and Science in Sports and Exercise. 38(8): 1451-61, 2006.

    (2) Grandados J, Gillum TL, Christmas KM and Kuennen MR. Prohormone supplement 3ß-hydroxy-5a-androst-1-en-17-one enhances resistance training gains but impairs user health. Journal of Applied Physiology. 116:560-569, 2014.

    (3) Gov.uk, (2010). Controlled Drug Lists – Publications – GOV.UK. [online] Available at: https://www.gov.uk/government/publications/controlled-drugs-list [Accessed 16 Sep, 2014].

    (4) Maughn RJ. Quality assurance issues in the use of dietary supplements, with special reference to protein supplements. The Journal of Nutrition. 143(11):1843-1847. 2013.

    (5) Npabodybuilding.com, (2014). Join the NPA – Natural Physique Association. [online] Available at: http://www.npabodybuilding.com/EntryForms.aspx#banned [Accessed 14 Sep, 2014].

    (6) Bnbf.co.uk, (2014). Banned List. [online] Available at: http://www.bnbf.co.uk/banned-list.html [Accessed 14 Sep, 2014].

    (7) Drugfreebodybuilding.co.uk, (2014). [online] Available at: http://www.drugfreebodybuilding.co.uk/INBFWNBFBannedSubstanceList.pdf [Accessed 14 Sep, 2014].

    (8) Worldnaturalbb.com, (2014). Banned Substances. [online] Available at: http://worldnaturalbb.com/wadabannedsubstances.html [Accessed 14 Sep, 2014].

    (9) Drugfreeathletescoalition.com, (2014). Banned Substance List. [online] Available at: http://drugfreeathletescoalition.com/wp/membership-subscriptions/banned-substance-list/ [Accessed 14 Sep, 2014].

    (10) Naturalmusclenetwork.com, (2014). [online]. Available at: http://naturalmusclenetwork.com/DrugTestingGuidelines.pdf [Accessed 14 Sep, 2014].

    (11) Nationalgym.com, (2014). Drug Testing – NGA – National Gym Association – Personal Trainer Certification – Natural Bodybuilding Contests – Professional Fitness Trainer Courses. [online]. Available at: http://www.nationalgym.com/national-gym-drug-testing.html [Accessed 14 Sep, 2014].