Bioavailability, Androgenicity, And Estrogenicity Of DHEA

Discussion in 'Scientific Studies' started by haidut, Aug 15, 2015.

  1. haidut

    haidut Member

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    I know that some forum members are considering taking or already are taking DHEA. As Peat has warned, and several studies confirmed, DHEA can be converted quite easily into estrogen if the dose used is too high or the person is under stress. In addition, there is some confusion about what route of administration is best. Below is a study that brings some clarity to the issue.
    The bottom line is this - the androgenicity / estrogenicity of DHEA depends on the route of administration. Percutaneous (transdermal) administration has androgenicity:estrogenicity ratio of over 10:1, subcutaneous has a ratio 3:1, and oral has a ratio of 2:1. In other words, transdermally applied DHEA is highly androgenic compared to oral route. The subcutaneous route of administration (achievable only by injection of hormone pellets) has the highest bioavailability (100%), but transdermal is not that far behind (33%) and oral is the worst (3%) in terms of bioavailability. Also, somewhat surprisingly, the subcutaneous administration was more estrogenic than percutaneous (transdermal). So, if estrogenicity of DHEA is your concern then applying it topically should not only give you much better bioavailability than oral (and not far behind subcutaneous) but the vast majority of DHEA should end up metabolized as DHT and T.
    My take is that these effects are due to the fact that the human skin is the organ with the second-highest expressions of the enzyme 5-AR responsible for the conversion of T into DHT. In addition, if DHEA is applied in a body area without much fat under the skin the expression of aromatase is probably low, which keeps DHEA from converting into estrogen and leaving most of intact for conversion into androgens. With oral administration, DHEA passes through the liver, which has relatively high expression of aromatase compared to skin. Also, subcutaneous avoids contact with the skin so the enzyme 5-AR will not get much chance to do its work on converting DHEA into DHT.

    High bioavailability of dehydroepiandrosterone administered percutaneously in the rat. - PubMed - NCBI

    "...As shown in Fig. 1, the percutaneous route is 10- to 15-fold more effective than the oral route. In fact, by the oral route, the highest dose of DHEA used, namely 30 mg, led to only a 40% reversal of the inhibitory effect of ORCH on ventral prostate weight while the 10 mg dose of DHEA by the percutaneous route increased prostate weight to a value not significantly different from intact controls...Taking the bioavailability of the subcutaneous route as 100%, it can thus be estimated that the percutaneous and oral routes have bioavailabilities of 33% and about 3% respectively."

    "...Taking intact male and female rats as standard references for androgenic and estrogenic activities respectively, DHEA administered subcutaneously is 3 times more androgenic than estrogenic while after percutaneous administration, the compound has 10 times more androgenic than estrogenic activity. The 3-3-fold decrease in the ratio of estrogenic to androgenic activities of DHEA administered by the percutaneous compared with the subcutaneous routes is probably secondary to variable access to the steroidogenic pathways leading to different ratios of androgens and estrogens by the percutaneous and subcutaneous routes."
     
  2. sugar daddy

    sugar daddy Member

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    This is interesting
    I have DHEA is tablets, is it possible to make these into a transdermal application with a liquid?
    And would it be best to apply to wrists or top of feet because of the lower fat?
     
  3. schultz

    schultz Member

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    Amazing!
    Do you know what kind of solvent was being used in this study?
     
  4. FredSonoma

    FredSonoma Member

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    Awesome thanks Haidut! Would it make any difference if someone was hypo? Would this actually help bring thyroid function up?

    Also, if someone is hypo, would it make sense to be on a thyroid supplement before trying DHEA?
     
  5. OP
    haidut

    haidut Member

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    You can try dissolving them into clear alcohol like vodka. It won't be as bioavailable as when dissolved in DMSO and pure ethanol but it can work and it is cheap.
     
  6. OP
    haidut

    haidut Member

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    Yes, they used a mixture of 50% ethanol + 50% propylene glycol. In our supplements we DMSO + ethanol so the bioavailability is close to 100%. In other words, the same bioavailability as the subcutaneous method and highly androgenic.
     
  7. OP
    haidut

    haidut Member

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    Since DHEA inhibits 11b-HSD1 it will lower cortisol synthesis. In addition, it is a glucocorticoid receptor antagonist. The combination of these effects means that if you are running on stress hormones DHEA may lower them and if thyroid is low you may feel sluggish. I think even Peat recommends taking some thyroid while taking DHEA. This may be one of the reasons.
    I personally do not feel the need to take thyroid when I take Pansterone. The pregnenolone in Pansterone boosts metabolism enough so that I don't need thyroid. But if it makes you sliggish, then some extra thyroid may help.
     
  8. Such_Saturation

    Such_Saturation Member

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    So 10mg is only good for oral?
     
  9. OP
    haidut

    haidut Member

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    What made you think so - the study? They do mention oral 10mg but it was in rats and the dose for a human would be different.
     
  10. narouz

    narouz Member

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    I guess I'm wondering if the study suggests:

    1. you can administer more to skin with DMSO,
    because it will mostly convert to androgens,
    or
    2. because it is so much more potent via skin DMSO,
    we should take much less...like no more than 1 or 2 mgs
     
  11. Such_Saturation

    Such_Saturation Member

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    Well... five times better conversion and ten times better availability...
     
  12. OP
    haidut

    haidut Member

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    The study with humans using topical administration found no estrogen increase until the daily dose reached 18mg. Androgens kept increasing for all doses. So, it seems that by using DMSO we can get a much bigger percentage of DHEA to convert into androgens if we stay under 18mg daily. There is another study that I will post on Monday showing 40% - 60% of the topically applied DHEA converted into DHT. So, this means getting 7mg+ of DHT from 15mg DHEA daily. This is a LOT. I have seen several official sources claim that a healthy young male produces around 0.1mg DHT per day. Not bad for a steroid officially labelled as dead-end in terms of relevance to human aging.
     
  13. narouz

    narouz Member

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    So...speculating here I know,
    but maybe then if Peat knew about these DMSO topical delivery studies
    he might think that much DHEA would be okay...?

    I haven't kept up with how he feels about DHT. :oops:
     
  14. Such_Saturation

    Such_Saturation Member

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    I tried it with vodka on my skin. I must say that just putting the powder under my tongue seems to give more results.
     
  15. OP
    haidut

    haidut Member

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    Cool, thanks. Technically speaking, under your tongue is still topical administration. What results did you get - mood, libido, muscle tone, etc?
     
  16. OP
    haidut

    haidut Member

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    I have read transcribed interviews where he says that DHT is safer than testosterone, largely due to its inability to aromatize.
    As far as DMSO, I think when he was filing his patents the work with DMSO was fairly new and there were no products using it as a solvent/carrier. That combined with his interest in vitamin E probably tilted the scales in favor of developing a tocopherol product rather than a DMSO-based one.
     
  17. Such_Saturation

    Such_Saturation Member

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    It's great mood but less considerate of others. Less patient, and getting up and doing things is quite easy. The voice is more stable. It gets all warm under my tongue, but it might be the rice flour.
     
  18. OP
    haidut

    haidut Member

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    Thanks. Those are classic DHT effects. If you get anger and aggression, it means it is converting to estrogen.
     
  19. narouz

    narouz Member

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    What dosage do you like to use--under your tongue I mean...?
     
  20. Such_Saturation

    Such_Saturation Member

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    10mg; the capsule is 25mg, so I must eyeball two-fifths.
     
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