PEDs

How well do anabolic steroids work?

The title of this article is a rhetoric question nowadays. Of course they work. Take high dosages of anabolic androgenic steroids (AAS) and you will grow bigger and stronger. It's that simple. Even the biggest potatoes on the internet acknowledge that anabolic steroids work, albeit some say they 'only work a little'. However, in past times this issue was still up to some debate in medical literature. It wasn't proven that steroids made your muscles grow or make you stronger. That took a few decades. I guess this is where some of the aversion against medical specialists stems from when it comes to anabolic steroid use.

Testosterone works very well when combined with resistance training

In 1996, a milestone study examining the effectiveness of anabolic steroids for muscle growth and strength in healthy young men was published and this put a definitive end to any debate that remained [1]. (If there was a single study about anabolic steroids I had to recommend reading, it would be probably be this one). The study compared the following four situations with each other:

  • No exercise + placebo (n = 10)
  • No exercise + 600 mg testosterone enanthate weekly (n = 10)
  • Strength training + placebo (n = 9)
  • Strength training + 600 mg testosterone enanthate weekly (n = 11)

The study lasted 10 weeks and the results were, without exaggerating, awesome. Before and after the intervention, the researchers measured body composition using underwater weighing, muscle size using magnetic resonance imaging (MRI) and muscle strength by a 1-repetition maximum (1-RM) on the bench press and squat. All the groups were controlled for adequate energy (36 kcal/kg bw) and protein (1.5 g/kg bw) intake.

In the two no exercise groups, there was no significant increase in fat free mass (FFM). However, I would like to point out that the increase was 0.8 kg in the placebo group vs. 3.2 kg in the testosterone group. It is in my line of expectations that the testosterone group would gain some muscle and perhaps some water. Both would show up as a FFM increase (I'll come back to possible water retention further down when discussing a follow-up study.) Therefore I suspect that the lack of a significant difference was because of a so-called type II error (a 'false negative', not finding a significant difference when there actually was one). After all, the group sizes were quite small. Small group sizes require larger effect sizes to find statistical significant differences.

Moving on to the strength training groups, both gained a significant amount of FFM. Not surprisingly, the testosterone group gained significantly more than the placebo group. The placebo group only gained 2.0 kg FFM, whereas the testosterone group gained 6.1 kg. Let those numbers sink in for a moment. Strictly speaking: adding just 600 mg testosterone enanthate per week, which is arguably a beginners dosage for most bodybuilders, tripled FFM gains in this study. Finally, the percentage of body fat did not change significantly in any group. The raw data on this wasn't reported, so it's hard to say anything useful about it beyond this.

When looking at strength gains in the bench press, the no exercise groups gained no significant amount of strength. Interestingly, when looking at strength gains in the squat, the no exercise + placebo group did not gain a significant amount of strength (+3 kg), whereas the no exercise + testosterone group actually did (+13 kg). This suggests just taking testosterone makes young men stronger, and I'd say more muscular, while not doing anything at all. As expected, both strength training groups gained a significant amount of strength on both the bench press and squat. The ones getting a placebo gained 10 kg on the bench press and 25 kg on the squat. The ones getting testosterone gained 22 kg on the bench press and 38 kg on the squat. So between a placebo and testosterone, that's roughly a doubling in strength for the bench press and 1.5-fold gain in strength for the squat. It should be noted, however, that the strength increase in the bench press in the testosterone group was not significantly different from the ones getting a placebo. Again, this smells like a type II error.

I will discuss the data for the muscle size measurements briefly. Both quadriceps and triceps area, as assessed by MRI, increased significantly in both testosterone groups compared to their corresponding placebo groups.

An important caveat to this study, is that water retention could have influenced the FFM and MRI measurements. However, taken together with the strength data (and of course the decades of real world experience with anabolic steroid usage by athletes), this proof-of-principle study provided some solid evidence that supraphysiological dosages of testosterone make you stronger and more muscular.

I'd also recommend reading Lyle McDonald's article on this. He has written about this study in an article about anabolic steroids and muscle growth on his website.

Testosterone also seems to grow muscle and make you stronger without training

Anyhow, having established that anabolic steroids actually work, the same research group investigated the dose-response relationship of testosterone in healthy young men [2]. They looked at the effects of 25, 50, 125, 300 and 600 mg testosterone enanthate weekly on body composition, muscle strength and size. To make things even more interesting, this study lasted 20 weeks instead of 10 as was the case in the previous study. However, they explicitly instructed the men to not undertake strength training or moderate-to-heavy endurance exercise during the study. But trust me when I say that the results did not disappoint. Over the course of 20 weeks, the 125, 300 and 600 mg groups gained 3.4, 5.2 and 7.9 kg FFM, respectively, as assessed by underwater weighing. Dual-energy X-ray absorptiometry (DXA) showed very similar changes. Comparing these results to the previous study, these non-exercising individuals receiving 600 mg testosterone enanthate per week gained more FFM than the group which received the same amount in combination with strength training for 10 weeks. Ha. So much for hard work and dedication. Additionally, DEXA showed a significant pre vs. post decrease in fat mass in the 600 mg group (-2.0 kg) and underwater weighing showed a decrease too, albeit not statistically significant (-1.1 kg, P=0.11). There was an inverse correlation between change in fat mass and the log testosterone concentration, i.e. the more testosterone, the more fat loss.

And this study actually got replicated by Bhasin et al. some years later [3]. They wanted to address the question whether or not 5α-reductase inhibition (5α-reductase is the enzyme responsible for the conversion of testosterone to dihydrotestosterone (DHT). DHT is more potent in activating the androgen receptor than testosterone.) would attenuate testosterone's effects on muscle mass and some other stuff. To this end, they again administered 25, 50, 125, 300 and 600 mg testosterone enanthate weekly to healthy men aged 18 to 50 years. Additionally, they were assigned either a placebo or dutasteride (a potent 5α-reductase inhibitor) in combination with it. The 125, 300 and 600 mg groups who received a placebo in conjunction gained 3.5, 5.7 and 8.1 kg FFM, respectively, as assessed by DEXA. The 125, 300 and 600 mg groups who received dutasteride in conjunction gained 2.6, 5.8 and 7.1 kg, respectively. Pretty neat, right? (And for the record: there was no significant difference between the FFM gains made in conjunction with placebo versus in conjunction with dutasteride, so the conversion to DHT doesn't matter.)

At this point, probably some of you reading this will think "but yeah, that's just water". Nearly 8 kg of water is a lot don't you think? The researchers checked for water retention by measuring total body water using deuterium water dilution (a great method to do this) and comparing this to the FFM measurements [2]. If the ratio of total body water to FFM would increase, this would be indicative of water retention. What they found was that this ratio did not significantly change in any of the groups, thus suggesting the increase in FFM was not due to water retention. These results do require some further explanation, as there are, in all honesty, some caveats to it. I think the most important caveat in this case is that the method simply is not sensitive enough. I will illustrate this point with an example using the group receiving 300 mg testosterone enanthate weekly. At baseline, this group had 66.9 kg FFM. The ratio of total body water to FFM was 61.6 %. A quick calculation will then give you the total body water, namely 41.2 kg. The group had gained 5.5 kg FFM at the end of the study. Now let's assume this was literally all water. So FFM went up from 66.9 to 72.4 kg and total body water went up from 41.2 to 46.7 kg. If you now calculate the ratio, it is 64.5 %. And what ratio did they exactly measure at the end of the study? 64.6 % (The reason I picked this group, was because the data matched this calculation almost perfectly. You can see similar changes in the ratio in the other groups though.). So, unfortunately, this point alone proves this method useless. It's simply not sensitive enough. Even while I assumed this group only gained water, it apparently was not statistically significant (and funnily enough matched their actual measurements).

More conclusive evidence, lies in the MRI measurements of thigh and quadriceps muscle volume. Thigh muscle volume increased by 6.3, 9.9, and 15.7% in the 125, 300 and 600 mg groups, respectively. Quadriceps muscle volume increased by 4.1, 8.7, and 14.4% in the 125, 300 and 600 mg groups, respectively. While water retention could have definitely affected the FFM measurements to one degree or another, these muscle volume measurements do strongly support a large degree of actual muscle growth.

In a follow-up publication, the researchers also demonstrated that the increases in muscle size of these young fellas was due to muscle fiber hypertrophy [4]. How did they determine this? Well, they took muscle biopsies from 39 of the 61 men who participated in the study. It is unclear how they selected these 39 men, perhaps the other men didn't like the idea of a muscle biopsy... Nevertheless, this does leave room for bias. Either way, they started the painstaking process of 'point counting' to determine the fiber cross-sectional area (CSA), and counting the actual number of fibers to determine whether or not hyperplasia (an increase in fiber number rather than size) took place. As with the increase in FFM, they found a testosterone concentration-dependent increase in fiber CSA.

Additionally, they found a significant increase in the myonuclear number per fiber in the men receiving 300 mg or 600 mg of testosterone enanthate. A finding which was also correlated with the testosterone concentration. They also report an increase in satellite cell number in yet another follow-up publication [5]. There's some debate in the literature about the relevance of the addition of new myonuclei, or satellite cell activity actually (cells which 'donate' their nucleus to the muscle fibers), in muscle hypertrophy. In a nutshell, muscle fibers rely on satellite cells for new nuclei. These nuclei contain DNA, which ultimately functions as the blueprint for the proteins a muscle fiber can produce. It is argued that, if a muscle fiber needs to keep on growing, it also needs to keep on getting more of these nuclei. Regardless of the debate about its relevance, recent evidence does suggest it's probably important. Good quality research has unequivocally demonstrated that satellite cells are required for overload hypertrophy to occur [6]. Additionally, the increase in myonuclei due to hypertrophy is suggested to lie at the heart of peripheral muscle memory [7]. This boils down to the fact that once acquired myonuclei appear to be somewhat permanent, or atleast stick around for many years. Consequently, this increase is proposed to support a higher level of protein synthesis. Given that these myonuclei seem to stick around for so long, it is therefore also suggested that previous steroid use, leading to an increase in myonuclei per fiber, yields an unfair advantage over those who never used steroids.

Now of course, these guys weren't big bodybuilders. But, I must emphasize they weren't your typical fat or skinny young men either. In the first study I discussed, the mean BMI of the exercise + testosterone group was 24.6 kg/m², with a fat percentage of 14 %. They also benched 97 kg at baseline. That's not bad at all. The participants in the sit-on-your-ass-for-20-weeks study had very similar anthropometrics. A later study carried out in bodybuilders (according to the study authors), tested the effects of 200 mg nandrolone (a testosterone derivative) decanoate per week over the course of 8 weeks in combination with resistance exercise [8]. The nandrolone group gained 2.6 kg of FFM, whereas the placebo group only gained 0.8 kg. Whilst 2.6 kg FFM is certainly a nice amount for that timeframe in bodybuilders, I also realize these results probably don't blow you away. But what must be realized is that they took a dosage that is on the low end of what is commonly used by physique athletes. Needless to say that higher dosages, which are more typically used by bodybuilders, would yield even better results. Moreover, relatively speaking they simply gained a multitude of the placebo group. The placebo group would take far longer to gain the same amount of FFM as the nandrolone group did. Again, with a relatively low dosage compared to what is common in the bodybuilding scene. And similarly to Bhasin et al, the authors did not find evidence of water retention. They used a more reliable method than Bhasin et al. for this. They not only measured total body water volume, but also extracellular water volume (by bromide dilution). By subtracting the extracellular water volume from total body water volume you can then obtain the intracellular water volume. This, together with their DEXA measurements, made the researchers confident that the increase in FFM was because of an increase in muscle mass.

Testosterone also works well in old men, albeit with more side-effects

Finally, Bhasin et al. have been so kind to also study the effects of graded doses of testosterone in older men (60 -- 75 yr old) [9]. The design of the study was similar to that of the study in young men lasting 20 weeks: old folks were randomized to 25, 50, 125, 300 or 600 mg of testosterone enanthate weekly and then they observed the magic for 20 weeks. Over the course of 20 weeks, the 125, 300 and 600 mg groups gained 4.5, 4.8 and 6.7 kg of FFM according to underwater weighing and again the DEXA measurements showed similar changes (+4.2, +5.6, +7.3 kg, respectively). As such, the authors concluded that older men are as responsive as young men to the anabolic effects of testosterone.

The 4.2 kg increase in the 125 mg weekly group seems suggestive of water retention. That dosage is slightly above what is used in testosterone replacement therapy (75-100 mg weekly) to mimic physiological testosterone levels. Nevertheless, it did more than double the testosterone levels of the men in this group. While they also measured water retention, they used the same method as in their earlier trial, which would simply not be sensitive enough to detect water retention. Glancing over the strength measurements (They measured strength by maximal voluntary strength in the leg press exercise by performing a one-repetition maximum.), there is a significant, but small improvement in the 125 mg group compared to the 25 mg group, but not the 50 mg group. Interestingly, the strength improvement in the 600 mg group was practically the same as the 125 mg group. This does support that water retention might have influenced the increases in FFM.

Anyways, so the men got a bit stronger and in the 600 mg group they even lost a whopping 3.0 kg of fat. Notably, however, is that there was a higher frequency of adverse effects in the older men compared to the young men. Specifically, hematocrit greater than 54 %, leg edema and prostate events (2 diagnoses of prostate cancer) occured numerically more frequently. The diagnoses of prostate cancer sound worrisome, but it's hard to relate this to the testosterone usage because of it's very low occurence. Out of the 8 people who dropped out in this study, 6 dropped out due to serious adverse effects (3 in the 300 mg and 3 in the 600 mg group). Older men seem more prone to (certain) androgenic side-effects than their younger counterparts

Anyways, in a nutshell, more anabolic steroids, more muscle growth, more muscle strength. They work!

References

  1. S. Bhasin, T. W. Storer, N. Berman, C. Callegari, B. Clevenger, J. Phillips, T. J. Bunnell, R. Tricker, A. Shirazi, and R. Casaburi. The effects of supraphysiologic doses of testosterone on muscle size and strength in normal men. N Engl j Med, 1996(335):1–7, 1996.
  2. S. Bhasin, L. Woodhouse, R. Casaburi, A. B. Singh, D. Bhasin, N. Berman, X. Chen, K. E. Yarasheski, L. Magliano, C. Dzekov, et al. Testosterone dose-response relationships in healthy young men. American Journal of Physiology-Endocrinology And Metabolism, 281(6):E1172–E1181, 2001.
  3. S. Bhasin, T. G. Travison, T. W. Storer, K. Lakshman, M. Kaushik, N. A. Mazer, A.-H. Ngyuen, M. N. Davda, H. Jara, A. Aakil, et al. Effect of testosterone supplementation with and without a dual 5areductase inhibitor on fat-free mass in men with suppressed testosterone production: a randomized controlled trial. Jama, 307(9):931–939, 2012.
  4. I. Sinha-Hikim, S. M. Roth, M. I. Lee, and S. Bhasin. Testosterone-induced muscle hypertrophy is associated with an increase in satellite cell number in healthy, young men. American Journal of Physiology-Endocrinology and Metabolism, 285(1):E197–E205, 2003
  5. I. Sinha-Hikim, J. Artaza, L. Woodhouse, N. Gonzalez-Cadavid, A. B. Singh, M. I. Lee, T. W. Storer, R. Casaburi, R. Shen, and S. Bhasin. Testosterone-induced increase in muscle size in healthy young men is associated with muscle fiber hypertrophy. American Journal of Physiology-Endocrinology and Metabolism, 283(1):E154–E164, 2002.
  6. I. M. Egner, J. C. Bruusgaard, and K. Gundersen. Satellite cell depletion prevents fiber hypertrophy in skeletal muscle. Development, 143(16):2898–2906, 2016.
  7. K. Gundersen. Muscle memory and a new cellular model for muscle atrophy and hypertrophy. Journal of Experimental Biology, 219(2):235–242, 2016.
  8. W. Lichtenbelt, F. Hartgens, N. B. Vollaard, S. Ebbing, and H. Kuipers. Bodybuilders’ body composition: effect of nandrolone decanoate. Med Sci Sports Exerc, 36(3):484–489, 2004.
  9. S. Bhasin, L. Woodhouse, R. Casaburi, A. B. Singh, R. P. Mac, M. Lee, K. E. Yarasheski, I. Sinha-Hikim, C. Dzekov, J. Dzekov, et al. Older men are as responsive as young men to the anabolic effects of graded doses of testosterone on the skeletal muscle. The Journal of Clinical Endocrinology & Metabolism, 90(2):678–688, 2005