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Why Does Testosterone Crystallise?

Testosterone Cypionate is more prone to supersaturation when compared with Testosterone Enanthate.  This makes it more susceptible to crystallisation under certain preventable circumstances, which will be explained in more detail later.

Manufacturers of cypionate globally provide the universal advice to inspect your testosterone medication for crystal particulate matter before administering (1-3).  If crystals are present, they recommend warming the solution and shaking to dissolve.  Investigation reports have reassuringly confirmed that this process doesn’t not negatively affect the testosterone in any way (4)(5).

Below is a ‘simple’ description of the differences between Testosterone Cypionate and Testosterone Enanthate.  I won’t detail how crystals can form, nor their structure configurations, as it’s lengthy.  Note the following image which is the structure of Testosterone Cypionate and Testosterone Enanthate, respectively (click for full size):

 

 

The esters attach, covalently, to the Oxygen atom to the furthest right of the Testosterone steroid.  The structure is completely different, despite the esters only differing by one carbon atom, if purely looking at their chemical composition. This structural difference, in addition to alteration of stereochemistry (note ester positioning, and this is a 2D picture!) will heavily influence several factors, such as the ability to form crystals.  For one, Testosterone Cypionate has two less rotatable bonds, which heavily affects the ability of Testosterone to be able to bind with other testosterone molecules in a crystal formation.  This doesn’t even include the number of electrons and other structural considerations.  Small changes can have large impacts. I’ll leave it at that though so that we don’t detail the chemistry too much.

One of the biggest contributors to crystal formation is super-saturation, ie. too much of a solute.  Think of too many tea bags in your tea, making it taste too strong!  To combat this, manufacturers often increase the volume of Testosterone Cypionate to 125mg/mL (250mg/2mL).  The next contributing factor is temperature; a temperature passing the threshold for crystal formation will indeed cause crystal formation.  The other factor is just bad luck – if you have a crystal already present and shake that solution, it’s more likely to ‘meet’ other testosterone molecules and potentially bind to it, forming a crystal – the temperature is ideal and the conditions are such that a crystal configuration can be formed.  Add the fact that users often push air into their testosterone vial when drawing their medication, and we’re just compressing the solution more which can mean a higher chance of creating a crystal formation.

We can really go into depths here with the actual chemistry behind this, but we won’t as it’s complex.  The bottom line is, it can happen, which is why manufacturer’s will alter the concentration in order to minimise this risk. This also isn’t to say it can’t happen with any other testosterone preparations, there are papers out there detailing the same thing with other esters, such as propionate (6) .  Unfortunately there is not a lot we can do about the laws of physics but the bottom line is that these medications are clinically approved and the crystals will not harm you.  Yes, it’s a pain to resolve and yes, you will need to warm your cypionate up prior to injecting if crystals are present, however please rest assured that it will not affect your Testosterone Replacement Therapy.

You can reduce the risk of crystals forming in your Testosterone Cypionate by following the advice below:

  • Do not unnecessarily shake the vial (be gentle and careful with it when transporting).
  • Store your vial in an insulated pouch to help avoid temperature fluctuations – we recommend epi-pen pouches such as these (available from clinic if required).
  • Keep in hand luggage rather than putting it into the hold when travelling (hold temperatures can be significantly lower than cabin temperatures).
  • Ensure that you do not inject any air into the vial when preparing and drawing your testosterone.  Sometimes, there is a small amount of air present in the syringe when taken out of the sealed packet, ensure that this air is completely expelled PRIOR to inserting into the vial.  Please email us if you require links to instruction videos on how to prepare and draw your testosterone medication.

 

References:

1.  https://www.sandoz.ca/sites/www.sandoz.ca/files/10033-Testosterone%20Cypionate%20Injection%20USP%20Product%20Monograph.pdf

2.  https://www.medsafe.govt.nz/Profs/Datasheet/d/Depotestosteroneinj.pdf

3.  https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/085635s029lbl.pdf

4.  https://pfe-pfizercom-prod.s3.amazonaws.com/products/hcp_depotestosterone.pdf

5.  https://www.sunpharma.com/sites/default/files/customer-letter-pdf.pdf

6.  https://pubs.acs.org/doi/10.1021/cg200640g