Too much testosterone kill brain cells.

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  1. Quote Originally Posted by Jayhawkk
    So what's your take on it Tsc?
    Assuming their research is sound, its still a matter of how much of an increase in brain levels will happen with X amount of extra test. ie, there is nothing there to say that the amounts they studied are indicative of what is actually happening with aas users.


  2. from last nights Conan (paraphrased)

    "When reached for comment about the findings of a study that say too much testosterone kills brain cells,
    Barry Bonds was qouted as saying 'Me hit ball' "

  3. ginker bilobers makes ya smerter me pappy sez

    woooo woooo

  4. In advance, I apologize for the long post. I impressed that most people haven't just dismissed this article outright. It is important that we don't discount something just because we don't want to believe it.

    That said; let me add my 2 cents worth. I am an immunotoxicologist by training, and don't pretend to be an endocrinologist or a neurobiologist. However, I do understand research. I do it for a living. JBC is an excellent journal, and method wise, this is a very nice study. However, my take on this study is that it is essentially meaningless.

    First, let's take a look at the premise of the research. I always put my research, and others that I review, through a test I think of as the "who cares" test. This came from when I was a postdoc, and I would show my advisor some interesting and clear-cut data, usually in vitro, and he would often say, "sure that's interesting what?" At first I was taken aback, but soon figured out that he didn't dispute there was a treatment effect, but he questioned the biological relevance of the experiment.

    So, according to the "so what" test, this study has little if any biological relevance that I can see--let me explain. First, as Enigma, CDB and others brought up, this study was done in vitro (petri dishes). There is a huge difference between tumor cell culture and primary cells, let alone a whole organism. A whole organism is incredibly more complicated, and tissue culture CANNOT model endocrine/organ/cell-cell interaction effects. This is a fact shown over and over again. RNAi is cool and all, but if they really wanted to support their hypothesis, a rat or mouse study using osmotic pumps and a direct assessment of brain pathology would have been far more convincing.

    Next is the question of an associated human pathology. The NIH has really been pushing toxicological studies to start from a pathology, then link a toxicant to it, rather than visa versa--which was how things used to be done. In this case the author supposes that some ambiguous yet real neurological conditions associated with as use such as aggression and depression are the result of neurological damage. However, the author sites no studies that this is indeed the case, and a quick pubmed search confirms that there is no evidence (neither epi nor case studies) that as users display any abnormal brain physiology as compared to normal subjects. Now, of course this could just mean no one looked. However, as use didn't start yesterday and one would assume that postmortem exams have been done in the past on as users who died of mysterious circumstances. If ANY abnormalities had been found, politicians and the press would have jumped on it immediately to save us poor deluded citizens from our self-destructive ways. Yet, strangely there are no reports to support this. Granted, I (uh, hypothetically) too have experienced transient mood fluctuations while "on" and during post cycle therapy as many or most have. Yet these changes are just that, transient. If toxic damage was occurring, one would assume there would be a chronic component since the CNS isn't suppose to regenerate (I say "suppose" because there is evidence of late that says it might). I still believe that mood swings are more of a component of screwing with the HPTA axis, rather than neurological damage--a belief that can actually be supported by published research.

    So, for grins, lets say that high dose test is a neurotoxicant, and no one has systematically looked for neurological abnormalities in users. How about anecdotal evidence? Really here, all one has to do is look at long term as users. If as were potent neurotoxins, wouldn't you expect a very long time user to act more like say...Mohammed Ali, rather than the governor of California? If this were true, then a significant proportion of long time as users would be patients in mental or rehab hospitals, and there would be a "anabolic steroid induced dementia" or some such pathology on the books already (yet there is not). I know some old school users (one in his 60's) from my gym and they all seem absolutely normal. Additionally, this study just gives evidence that as are general neurotoxins, and one needs to keep in mind that the brain isn’t just cognition and emotion. If this were true, how come users don’t experience any motor difficulties either peripherally or centrally? Do pro athletes get better or worse at their sport with as use? As a personal note, my wife is an Occupational Therapist and has never seen a strength athlete in her 15 years of rehab experience with neurological deficits from anything other than trauma.

    Next, lets look at the nuts and bolts of the study. With any tox study, one always has to be extremely careful about dose. You have to choose a biologically relevant dose, and back up your choice with sound research. The authors in this case choose 100 nM test as their "normal" dose and 1uM as their low toxic dose. Okay, that sounds fine superficially, since Bhasin et al (NEJM 1996) treated healthy men with 600mg/wk of test enanthate for 10 wks, and final total test was about 3244 ng/dl which works out to be 811nM or 0.81uM (jeeze, I hope I calculated right--I won’t be offended of someone checks my math). However, (and this may be the deal breaker--again if my math is right) they don't take into account the buffering capacity of SHBG as Enigma alluded to earlier in this thread. While the men in the Bhasin study had near 1uM of total, their FREE test was only 143nM, which is well below the authors lowest significant toxic level, and nearly 100 times lower than the extremely toxic level of 10uM. So, really what this study shows that a person on around 600 mg/wk of test has nothing to worry about--which is not what they conclude from their own data.

    So, all in all, I wouldn’t get too worked up about this study. Now, if they repeat this in an animal model…

  5. "In this case the author supposes that some ambiguous yet real neurological conditions associated with as use such as aggression and depression are the result of neurological damage."

    That's the part that gets me. She makes this broadbrush statement about behavioral changes when there is a host of data showing completely different mechanisms for this other than nuerotoxins.

    Has she ever looked into dopamine elevation from increased test use, or the various changes in serotonin parameters brought on by alterations to cholesterol values and ratioes? I doubt it. She got interviewed by Rueters and decided to become the voice of male endocrinology which is horribly irresponsible IMO.

    The study doesn't take into account numerous in vivo mechanisms. It may very well be the ratio of E to T that is the important factor or SHGB buffering as you mentioned.

  6. I absolutely agree.

    Honestly, I am surprised this got published in such a respected journal. I suspect it was because of the methods employed (siRNA is very sexy), and the controversial/news-worthy nature of the study. JBC got some nice press out of this, didn't they? If they had submitted it to a toxicology journal, it would have been rejected based on these very criticisms.

  7. oh man i got college finals comin up to.... I guess if i start staring at the wall in a daze for 30 min and then all the sudden bang on the desk while simultaneously ripping my paper in half and yelling at the girl behind me,.. i guess i'll know why.


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