In depth – Creatine Supplementation and Androgen Metabolism

There has been some concern as of late with creatine being implicating in increasing the Testosterone:DHT ratio in healthy volunteers, mainly as DHT is more androgenic and encourages hair loss [x] (in those genetically susceptible to androgen-induced hair loss) due to being both more potent and staying at the androgen receptor longer. [x]

The purpose of this article is to elucidate these relations, the main articles under review are:

These three were chosen as it includes the primary study under review, a response to the primary study, and another from alternate researchers looking at creatine’s effects on hormones.
Study Design
From what I can tell, it is a well designed study. Two groups of 18-19 year old males with no prior usage of supplementation were assigned to two groups, a control and experimental. Control group was 50g glucose daily for 7 days, followed by a maintenance dosage of 30g glucose for 14 days (total 21). Experimental group was 25g creatine monohydrate and 25g glucose for 7 days with a maintenance dose of 5g creatine monohydrate and 25g glucose for 14 days (21 total). After the first 3 weeks of the experiment there was a 6 week washout period and then the groups were reversed (those who were in control first time around were now experimental).
Given the compound is excreted throughout the washout period (which creatine is in 6 weeks), then the cross-over design is very robust in being able to factor out genetic factors.
Overall Results
The chart below shows the overall results of the interventions:
My main concern here is that the creatine supplemental group initially had lower testosterone levels than the control group, and remained lower throughout the whole study. The authors did not address this difference per se, but only acknowledged that ‘overreaching and overtraining can reduce testosterone levels’.
If there exists a recomponsatory mechanism in the body where in states of testosterone deficiency there is more alpha-5-reductase activity to balance out androgen metabolism (theoretically plausible as, since DHT is more androgenic, this would be a homeostatic mechanism of androgen receptor kinetics) and this upregulation has a long time to return to baseline, then it could skew the entire results.
Similar to other studies, no changes in testosterone levels were noted with supplementation. [x]

Statistical Power
Although this is a stand alone study at the moment, the statistical power is quite impressive (at least as far as can go with Student unpaired T tests, and Tukey tests for time intervals). Although a statistical significance factor was set at (P < 0.01) (meaning that it has a 1/100 chance of being due to pure chance), the conclusion statement (DHT increased by 56% after 7 days and remained 40% above baseline for 14 days) has statistical power of P < 0.001 and increases in DHT concentration over time were significant at P (< 0.00001); the significance of the ratio between T:DHT was P (< 0.000001).
Unless the math was otherwise botched, these results suggest damn near no probability it was due to chance (and if a study by another group replicates this design and finds the same significance, it would be a very powerful combination of results). If any flaws are with this study, it is in methodology.
Meta-discussion
(Essentially, my discussion on their discussion)
The authors noted that ‘no players became overreached or overtrained’ during the experiment, as there was a 2 week mid-season break. All subjects were on the same diet, so its unlikely that the control group ate nothing while the experimental group ate loads.
In the response to the study, Gary Green (MD) of UCLA noted that the authors did not disclose the source of, nor independently test, the supplement. Purity was not known, and thus potential for flaw lays there. In response to that claim, the original authors disclosed that the supplements were analysed by HFL Sports Science Inc via gas and liquid chromatography mass spectrography tests. It was determined both pre and post trial as relatively pure, specifically:

An ultraviolet scan between the wavelengths of 200 and 360 nm revealed no interferences except
for creatinine.
In the discussion the authors mention differences in DHT:T ratios depending on ethnicity, but ethnicity was not recorded in this study. [x]
The authors hypothesized that the effects seen were not located in the muscle, as no 5-alpha reductase enzymes exist in muscle tissue (or at least, a very low amount). [x]
Results that were not primarily under review but were also found were greater body weight increases in the experimental group with concurrent reduced sum of 6 skinfolds (body fat test) indicative or more lean mass gained; body fat percentage and lean mass also showed beneficial trends in the experimental groups. This, however, was not clinically significant and could have been due to other factors as the study duration was long (12 weeks).
Future Research
The authors themselves noted that these results are preliminary at best:
Because of the potential clinical relevance of the endocrine
results of this study and the high frequency of individuals
using creatine supplementation without monitoring, further
investigation is warranted.
Personally, I would wait for future research on the topic before making any conclusions. In particular, I would like to see a study where both the control and experimental groups had the same level of testosterone prior to creatine intervention to rule out the possibility of upregulation of 5-alpha reductase in response to reduced testosterone levels.

Connect with Facebook

Comments

  1. 2ndLaw says:

    Any thoughts on combining Triazole with creatine?

  2. Silverhydra says:

    Looking at the ingredient list, I see no reason why the two would not compliment each other. I saw go for it.

  3. hggh says:

    Hodge twins say no at 37 yrs old http://www.youtube.com/twinmuscleworkout#p/search/10/EtTbb8StDRs I heard in a latest video they are cycling -off- it for a while.

  4. Silverhydra says:

    That video failed to establish any point whatsoever; the study in question *did* not an increase in DHT levels independent of testosterone so….yeah.

    “If a scientist claims to have proven it, tell him I said fuck off”

    Really?

Speak Your Mind