Why do some people respond better than others to steroids?  One reason is genetics, and one particular gene called PDe7B is giving us some unique insight into how our bodies handle testosterone enanthate.

In the last article I mentioned the large varying response men in a study on testosterone enanthate had after one 500 mg intramuscular injection.   As a reminder one hyper responder had serum testosterone levels of 3300 ng/dL 4 days after the shot, while a low responder had levels of only 1000 ng/dL.   The authors of that paper mentioned the low response, and hyper response of some individuals may be a result of the phosphodiesterase 7B gene or PDE7B.

While research on the PDE7B gene is in its infancy, there are a couple of very interesting papers on its effects with anabolic steroids.  Before I get to those, remember that injectable steroids are in a depot oil.  Once injected the depot oil slowly releases the steroid into the body to exert its various anabolic actions.  Two common steroids are testosterone enanthate and nandrolone decanoate (or “deca”).  Before the body can utilize testosterone and nandrolone it first needs to “drop off” the fatty esters enanthate and decanoate.  This process is referred to as hydrolysis.

Up until recently it has been relatively unknown which enzymes “activate” testosterone and nandrolone by causing the removal of their enanthate and decanoate esters.  One such enzyme that is known to metabolize and remove (glucuronidation) steroids is UGT2B17.  People with a UGT2B17 gene polymorphism have trouble excreting/removing testosterone (at least this is what has been seen in urine).  So it’s believed this will also result in higher blood levels of testosterone.

To test this belief researchers gave 51 men (average age of 30) one 500 mg shot of testosterone enanthate and tested their serum blood levels before, and 2 days after the shot [Reference].  Of course they found that the range of testosterone levels in the men varied wildly.  So they took 5 guys with the highest levels, and 5 guys with the lowest levels, and completed a DNA analysis (affymetrix).  This helped identify PDE7B as one gene that may cause the differences in serum levels of testosterone after injection.  The DNA analysis resulted in 300 different SNP’s (“snips”), 12 of which were associated to the PDE7b gene (SNP’s defined).  Since the PDE7B gene seemed causative they identified two of the twelve SNP’s to further analyze.

  • rs7774640
  • rs4896187

aas hyper responderSo we know the PDE7B gene plays a large role in determining our genetic response to testosterone (roughly 36%), but how much so, and which gene trait do we see in hyper responders?  To answer this they compared alleles of the hyper responders and the low responders.  An allele is simply a variation of the gene.  Guys that were homozygous GG were low responders.  While guys with a one or two A alleles (AG, or AA) were hyper responders.  How much did this matter? A lot.  Guys with the GG allele had an increase in testosterone about 2.5 fold after injection.  While guys with an A allele experienced a 3.9 fold increase in testosterone after injection.

The original hypothesis, that those with a UGT2B17 gene polymorphism would have higher serum testosterone levels, was not substantiated in this paper.

“The overall fate of testosterone in individuals devoid of the UGT2B17 enzyme is yet to be identified.”

As a final note on this testosterone enanthate paper, by Day 2 the average testosterone level increased 196% after the 500 mg injection (DHT levels increased 88%).

How to Predict Your Response to Testosterone Enanthate

Genetics are complicated.  But what if you could know, before you ever used steroids, how well you might respond to them?  If you found out you would have a very low response, maybe they wouldnt be worth your risk or time.  Or if you might be a hyper responder, perhaps you would consider using them.

I decided to try and find out my genetic response to anabolics.  A few years ago I completed a 23andMe DNA analysis.  This is a popular site that has been under some FDA scrutiny.  Nonetheless one of the benefits of this service is their Raw Data.  In your Raw Data you can look up a specific gene and SNP and find out which allele you were genetically blessed to have.  Unfortunately of the 100+ SNP’s that 23andMe tests for on the PDE7B gene, neither of the two analyzed in this study were included.  And only 1 of the 12 found in the affymetrix was – SNP rs10872455.  Of course I’m homozygous for the G allele (that could mean I am a low responder, which wouldnt really surprise me).

Ultimately if a company like 23andMe offered a reasonably priced test for the PDE7B rs7774640 SNP I would encourage all anabolic seeking bros to check it out.  Maybe there is already one that exists that I am not aware of?  If you know of such a test, please share below.

2 thoughts on “Finding out your Genetic Response to Steroids – Low vs. High Responders

  1. Shaun Thomas says:

    Great article.They might be termed low responders but a 2.5 fold increase in testosterone surely is massive

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