Monday, April 20, 2015

BroScience Research: "What do Bros Say About AAS Use and the Prevention of Shut Down & Infertility?"

Are today's "muscle men" not going to be able to procreate?
If you are frequenting any of the popular fitness and bodybuilding bulletin boards, you will know that "broscience" is a mixture of anecdotal evidence and hilarious claims that is spiked with cherry picked scientific references.

Against that background it may sound funny that researchers from the New Castle Fertility Center devoted a complete study to the analysis of drugs and protocols highlighted by the online community of users for prevention and/or mitigation of adverse effects of steroid use. If you think about it, however, it's only logical that doctors will be better able to help their patients if they understand what brought them in a situation in which they have to see a doctor at a fertility clinic.
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With the ever-increasing lifetime prevalence of AAS use in men being currently estimated to be between 3 0 and 4 2% (de Souza. 2011), it is after all not unlikely that many of the future patients of fertility clinics all over the world may suffer from the long-term consequences of AAS abuse - regardless of whether they belong to those 50% of AAS userswho tell their doctor about their stroid history or not (cf. Pope. 2004). This mistrust does not exist by chance, though. As Karavalos et al. (2015) point out in the paper at hand,
"[...] mainstream academic endocrinology rather lost credibility with the ‘performance-enhancement community’ in the 1980s and 1990s, by persisting overlong in (a) doubting whether further enhancement of athletic performance could be achieved through raising serum T levels above the physiological reference range and (b) questioning whether any therapeutic separation of androgenic and anabolic actions was achievable, due to the single androgen receptor (cf. Pope. 2004)" (Karavalos. 2014).
And let's be honest. Someone who actually believes that superphysiological doses of AAS were not performance enhancing might actually learn something something from the broscientific expertise of his clients... well, as long as he is willing to listen to what they have to say.
Figure 1: Illustration summarizing the keywords (left) the scientists used to select the top 20 websites, blogs and forums (right) they researched for information on the use of AAS and means to prevent side-effects (Karavalos. 2015).
As previously mentioned, Karavalos, Reynolds, Panagiotopoulou, McEleny, Scally an Quinton, the authors of the paper at hand were  willing to listen. They used Google, the most popular online search engine (Search Engine Watch, 2012), along with the search terms listed in Figure 1 to identify Internet sites related to methods and substances used to counteract the symptoms of hypogonadism secondary to exogenous steroid use and selected the top twenty links generated by their search (Figure 1) and navigated through them to obtain details of
  • the methods and substances advised to counteract the side effect of hypogonadism and
  • the quality of medical information and advice provided online
Unsurprisingly, the best, i.e. most relevant not "best" as in medially correct, results were yielded by utilizing the terminology the AAS users commonly use, such as ‘postcycle therapy’, ‘stacking’ or ‘steroid recovery’.
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"We found that online discussions and advertisements concerning agents that can be used to combat the side effect of hypogonadism are very common. There was a mixture of information available from online communities (forums), AAS user blogs and from websites attempting to sell products such as anabolic steroids and substances directly related to hypogonadal recovery. Roughly one-third of the Internet sites we reviewed also offered to sell these drugs without prescription. Information was also available from official public health websites, such as the Welsh government funded and image-enhancing drugs website (SIED The later provided risk reduction advice by provid ing information on safe injection practices" (Karavolos. 2014)
As I already hinted at in the introduction the information on forums consisted of anecdotal reports and advice from unverifiable sources (some claiming to be medically qualified). These sources referenced mainstream scientific papers and abstracts on the issues discussed.
"However, there were clear flaws to this superficially ‘evidence-based approach’. The papers quoted were of only limited generalizability to AAS users, ASIH, or to the argument proposed by the ‘expert’. Equally most users were unable or unwilling to progress beyond subscription paywalls, leaving them to draw conclusions from the abstracts or the ‘expert opinion’ alone" (Karavolos. 2014).
The most commonly named drugs and supplements to bring back normal endocrine and liver function were clomid or nolva, toremifene, and raloxifene, various AIs (anastrozole, letrozole and exemestane) as well as stacks consisting of milk thistle blended with a multitude of ingredients, such as vitamins (notably vitamin D), minerals (most often zinc), amino acids, herbal extracts and compounds such as L-carnitine. While the effects on the HPTA were discussed in detail, potential long-term effects on spermatogenesis were largely ignored. In fact,
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"[...] discussions often lead to misunderstanding the pathophysiology of spermatogenesis and its impairment, leaving users to believe that return to normal serum testosterone levels translated to normal spermatogenesis.

In most discussions, men seemed to equate regaining endogenous steroid production to normal fertility, ignoring long-term effects on quality of sperm, such as poor morphology and motility, which might potentially be irreversible." (Karavolos. 2014).
The problem with this assumption is that normal spermatogenesis is associated with intratesticular T levels some 30-fold higher than serum T levels. Exogenous administration cannot deliver anything remotely approaching this requisite T concentration within the seminiferous tubules; indeed, it will tend to markedly reduce it by suppressing endogenous LH-mediated T secretion.
It is hard to predict how long the natural T production will be suppressed: Aside from the drugs that were used and the duration, age appears to be an important factor, with younger users recovering significantly faster than older ones (Moretti. 2007).
Of the treatments mentioned on the boards, only two have some degree of scientific backup, albeit not exactly in form of reliable long(er)-term studies on former steroid users:
  • Figure 2: A meta-analysis of the use of  oestrogen antagonists (clomiphene or tamoxifen) as medical empiric therapy for idiopathic male infertility shows significant increases (∆ in %) in pregnancy rates, sperm concentration and motility as well as the "sperm production trigger" FSH in response to treatment (Chua. 2013).
    HCG, which has been successfully used for the treatment of T deficiency and/or induction of spermatogenesis in gonadotrophin-deficient adults (typically with concomitant FSH therapy in the latter role) and in treating hypogonadotrophic pubertal delay (Liu. 2002), and
  • SERMs such as clomiphene, tamoxifen and raloxifene which have long been used off-label for the treatment of male gynaecomastia and infertility, for which studies show highly variable success rates ad most promising data for clomiphene or tamoxifen in the treatment of idiopathic male infertility (Chua. 2013). How many of the subjects in the studies were infertile due to AAS (ab-)use is unknown, but in view of the low number of AAS users who speak openly about their steroid history, the rate could be high.
For disclosed steroid induced infertility there are yet only case reports available that suggest that either of these agents is an effective method to restore fertility in former AAS users. Strong evidence for the use of aromatase inhibitors (AIs) is absent.
In theory, SARMs may build muscle without any of the ill side effects of androgens, but their effects on fertiltiy as well as their long-term safety has not yet been studied sufficiently. Keep that in mind when you read my recent overview of the literature here and if you are seriously considering their use.
Bottom line: The study at hand confirms that most of the information you will find about the use of AAS on the Internet generates the false impression that "AAS use is safe with manageable adverse effects." This is in part due to the non-awareness of potentially long-lasting anti-fertility effects that may persist, for months if not years even if the normal HPTA function is restored.

Karavolos et al.'s comparison of bro- and pro-science does yet also reveal that not all the advise you can find "on the boards" is total bogus. The use of SERMs and HCG, for example, appears to be a still unproven, but at least promising strategy to normalize both, the production of testosterone and sperm after an AAS cycle. Still, far more research is necessary before we would be able to quantify the risk of long-lasting negative effects of AAS use on the endocrine axis and, even more so, on sperm production and function | Comment on Facebook!
  • Chua, M. E., et al. "Revisiting oestrogen antagonists (clomiphene or tamoxifen) as medical empiric therapy for idiopathic male infertility: a meta‐analysis." Andrology 1.5 (2013): 749-757.
  • de Souza, Guilherme Leme, and Jorge Hallak. "Anabolic steroids and male infertility: a comprehensive review." BJU international 108.11 (2011): 1860-1865.
  • Karavolos, Stamatios, et al. "Male central hypogonadism secondary to exogenous androgens: a review of the drugs and protocols highlighted by the online community of users for prevention and/or mitigation of adverse effects." Clinical endocrinology (2014).
  • Liu, Peter Y., et al. "Predicting pregnancy and spermatogenesis by survival analysis during gonadotrophin treatment of gonadotrophin-deficient infertile men." Human Reproduction 17.3 (2002): 625-633.
  • Moretti, E., et al. "Structural sperm and aneuploidies studies in a case of spermatogenesis recovery after the use of androgenic anabolic steroids." Journal of assisted reproduction and genetics 24.5 (2007): 195-198.
  • Pope, Harrison G., et al. "Anabolic steroid users’ attitudes towards physicians." Addiction 99.9 (2004): 1189-1194.