1. Orange & Red Light Therapy Device - LGS1
    CLICK HERE!
    Dismiss Notice

5α-Dihydroprogesterone (5α-DHP) - Pro-hormone And Neurosteroid For R&D

Discussion in 'IdeaLabs' started by haidut, Nov 23, 2016.

  1. haidut

    haidut Member

    Joined:
    Mar 18, 2013
    Messages:
    11,162
    Gender:
    Male
    Location:
    USA / Europe
    As many of you know by now, I have acquired an interest lately to research the connection between the process of saturation of various nutrients and steroids and the effects of this saturation on the properties of these substances. After doing some work on androgens such as androsterone and 11-keto DHT, I started researching the effects of various progestins / progestogens, especially metabolites of progesterone. As most people familiar with Peat know, progesterone occupies a rather prominent role in his writings due to its multitude of systemic beneficial effects such as opposition to estrogen, PUFA, aging, degeneration, infections, serotonin, prolactin, NO, etc. After reviewing the metabolic pathways of progesterone, especially in the brain, one metabolite immediately caught my eye. That metabolite was 5α-Dihydroprogesterone (5α-DHP).
    5α-Dihydroprogesterone - Wikipedia

    5α-DHP is formed from progesterone by the activity of the enzyme 5α-reductase (5-AR) - the same enzyme that converts T into DHT. I noticed that 5α-DHP levels rise sharply during pregnancy in most mammals (including humans) and in some species are the only progestogen as that species (horses) produces almost no regular progesterone. 5α-DHP is also the direct precursor to the neurosteroid allopregnanolone.
    Allopregnanolone - Wikipedia

    Allopregnanolone is the current darling of the pharma industry (since everything else failed) and is in clinical trials for almost every conceivable brain or mood condition including epilepsy, Alzheimer, Parkinson, TBI, MS, ALS, depression, schizophrenia, bipolar disorder, PTSD, suicidal tendencies, etc. Those trials are being conducted with both bioidentical allopregnanolone and its bastardized synthetic cousin Ganaxolone.
    Ganaxolone - Wikipedia

    Early animal studies and subsequent human ones showed that it is progesterone metabolites formed by the activity of the enzyme 5-AR that are primarily responsible for the beneficial effects of progesterone in the brain and in so many conditions. Administration of a 5-AR inhibitor like finasteride reliably lowers levels of not only DHT but also of 5α-DHP and allopregnanolone. The administratios of a 5-AR inhibitor abolished almost all positive effects of progesterone in the brain. This suggests that it is the 5-AR metabolites of progesterone such as 5α-DHP and allopregnanolone that are primarily responsible for the benefits of progesterone in all these conditions. Reductions in brain allopregnanolone are widely recognized as the single most important factor in mental health (especially depression, suicide, and the infamous "brain fog"). Virtually all SSRI drugs that have shown some effectiveness raise levels of allopregannolone in the brain. However, in people who are under stress, have neurological damage, have endured treatment with finsateride, or are simply loaded with PUFA the enzyme 5-AR is downregulated both in levels and in activity. As such, simply supplementing with progesterone may not have the desired effects of raising allopregnanolone. This may be one of the reasons why progesterone seems to lose effectiveness as an anti-depressant in older people - i.e. they have much lower expression and activity of 5-AR compared to younger people. However, with the widespread PUFA assault even young people are showing signs of diminished neurological responsiveness to progesterone when administered as a supplement. One option would be to supplement allopregnanolone. However, allopregnanolone is not available OTC or by prescription in any country. In addition, due to the recent successful trials with both bioidentical and synthetic allopregnanolone derivatives, the future of allopregnanolone as a freely available chemical looks rather bleak. In all likelihood, one the FDA approved allopregnanolone or Ganaxolone for any condition, the company behind the trial will petition FDA to start regulating allopregnanolone as a drug. In addition, while allopregnanolone has a great track record as neurosteroid, it has no progesterone effect - i.e. it is not an agonist of the progesterone receptor. Agonism of the progesterone receptor has a multitude of other benefits including opposition to estrogen, prolactin, serotonin, NO and variety of other mediators tat serve to inhibit metabolism. Thus, ideally the substance to be supplemented with should have the properties of allopregnanolone (or easily convert into it) while also having the properties of progesterone through the progesterone receptor. The steroid 5α-DHP is exactly such substance, and for now it seems to not be subject to any clinical trials or legal threats. It is a direct precursor of allopregnanolone and as such should elevate allopregnanolone levels even in people with strongly downregulated 5-AR - i.e. sufferers of the so-called post-finasteride syndrome (PFS), older people or people under severe stress or PUFA loads. Just like progesterone 5α-DHP is capable of reducing estrogen receptor levels inside the cells and knock the estrogen out of the cells. It also inhibits prolactin release, just like progesterone. More importantly, it achieve these benefits in doses 2-3 times lower than progesterone. And last but not least, 5α-DHP is not a metabolic precursor to estrogen, cortisol, and aldosterone like regular progesterone is.
    Furthermore, 5α-DHP (like other 5-AR derived steroids) can serve as raw material for synthesis of potent androgens such DHT, androstanedione, and androsterone. And unlilke other precursors such as DHEA, 5α-DHP does not seem to activate the same negative feedback mechanisms upon its conversion to DHT or other androgens.
    Finally, to top it all off, 5α-DHP does not seem to possess anti-androgenic effects like regular progesterone. This should make it a bit more convenient for supplementation in males who are wary of using progesterone supplements. I think the saturation of the steroid is what removes some if its anti-androgenic effects while preserving the activation of the progesterone receptor.

    Note: The opponents of DMSO on this forum have a reason to celebrate :) Due to its extremely lipophilic nature, 5α-DHP is almost insoluble in solvents like DMSO, ethanol, acetone, etc. The only solvent in which it dissolves in high enough concentrations to make it practically useful is tocopherol, and as such the solvent for this product is mixed tocopherols and MCT.

    The units listed on the label are just for measurement purposes. They do not indicate or suggest optimal dose. Please note that similar to the products sold by companies like BlueSky, this product if for lab/research use only. The product can be ordered from the link below:
    http://www.idealabsdc.com/lab

    *******************************************************************************
    5α-Dihydroprogesterone (5α-DHP) is a metabolite of progesterone through the action of the enzyme 5α-reductase (5-AR). It is an agonist of the progesterone receptor with similar potency to progesterone, and just like progesterone it is an agonist of the GABA receptor. As a result, 5α-DHP has been shown to possess a number of properties ascribed to progesterone, including anti-estrogenic, anti-prolactin, sedative, anxyolitic, anti-depressant, neuprotective, anti-aging, pro-metabolic, pro-thyroid, and anti-proliferative. Unlike progesterone, 5α-DHP is not a metabolic precursor to cortisol, estrogen and androsterone. However, due to its 5-AR derived nature 5α-Dihydroprogesterone (5α-DHP) can serve as a pro-hormone to potent androgens such as DHT, androstanedione, and androsterone through a recently discovered alternative pathway. 5α-DHP is also a direct precursor to allopregnanolone and can elevate its levels even in cases of severely downregulated 5-AR activity due to stress, PUFA overload, or administration of 5-AR like finasteride or dutasteride. Finally, unlike progesterone, 5α-DHP seems to have little or no anti-androgenic effects.

    Drops per container: about 240
    Each drop contains the following ingredients:

    5α-Dihydroprogesterone (5α-DHP): 1 mg

    Other ingredients: mixed tocopherols, MCT
    *******************************************************************************

    References:

    1. Po-hormone for DHT / androgen agonist / progesterone agonist
    5α-Dihydroprogesterone (5α-DHP) Is Androgen/Progesterone Agonist And Pro-hormone For DHT

    2. Anti-estrogen effects
    5α-Dihydroprogesterone (5α-DHP) Is More Effective Than Progesterone As Estrogen Antagonist

    3. Anti-prolactin effects
    5α-Dihydroprogesterone (5α-DHP) Is More Effective Than Progesterone In Lowering Prolactin

    4. GABA agonist and neurosteroid
    5α-Dihydroprogesterone (5α-DHP) - The Primary Progestogen Neurosteroid

    5. Effects on neurodegenerative conditions
    5α-Dihydroprogesterone (5α-DHP) - Potent Role In Neurodegenerative Conditions
     

    Attached Files:

  2. johnwester130

    johnwester130 Member

    Joined:
    Aug 6, 2015
    Messages:
    1,282
    for male.....rats ?

    or female rats ?
     
  3. Dhair

    Dhair Member

    Joined:
    Jul 29, 2015
    Messages:
    472
    Gender:
    Male
    What kind of effects have you noticed after experimenting with it, @haidut ?
    Also, could this be used with 11-keto-DHT?
     
  4. OP
    haidut

    haidut Member

    Joined:
    Mar 18, 2013
    Messages:
    11,162
    Gender:
    Male
    Location:
    USA / Europe
    Both, it seems to work equally well. The HED doses for lowering estrogen and prolactin are rather low - 10mg - 15mg in a single dose should lower estrogen receptor levels by up to 75% and prolactin release by up to 70%.
     
  5. OP
    haidut

    haidut Member

    Joined:
    Mar 18, 2013
    Messages:
    11,162
    Gender:
    Male
    Location:
    USA / Europe
    Just like androsterone - potent anti-depressant. The saturated steroids are really where it seems to be at for improving mood. Also, unlike androsterone which gave me a bit of unrestful sleep, 5α-DHP seems to be great to improve sleep. In higher doses (20mg - 30mg daily) I also noticed androgenic effects like harder muscles and leaner body. It also seems to be rather good for memory and cognition. It is not as sedative as progesterone, so it should be useful for studying but I think that effect is individual as one potent human anesthetic agent (pregnanolone) is a metabolite of 5α-DHP.
    I think it can also be used for flu protection, given the posts about progesterone being protective from both lethality and infectiveness of viruses.
    Is the "Man Flu" a real thing? Science says yes - Cantech Letter

    All in all, quite a versatile steroid.
     
  6. X3CyO

    X3CyO Member

    Joined:
    Sep 19, 2016
    Messages:
    226
    Gender:
    Male
    Location:
    Erf
    Any idea when cypro will be coming out? Wanna order both.
     
  7. OP
    haidut

    haidut Member

    Joined:
    Mar 18, 2013
    Messages:
    11,162
    Gender:
    Male
    Location:
    USA / Europe
    We should have it next week, probably by Wednesday.
     
  8. X3CyO

    X3CyO Member

    Joined:
    Sep 19, 2016
    Messages:
    226
    Gender:
    Male
    Location:
    Erf
    :dancingsmileyman
     
  9. Such_Saturation

    Such_Saturation Member

    Joined:
    Nov 26, 2013
    Messages:
    6,837
    EXTRA SATURATED
     
  10. Dhair

    Dhair Member

    Joined:
    Jul 29, 2015
    Messages:
    472
    Gender:
    Male
    You have a cypro product coming??? Damn that's just what I needed!
     
  11. OP
    haidut

    haidut Member

    Joined:
    Mar 18, 2013
    Messages:
    11,162
    Gender:
    Male
    Location:
    USA / Europe
    Lol, exactly my friend. I thought of you when I stumbled upon 5α-DHP.
    A bottle is on its way to Peat, so hopefully he will give some feedback on how he likes this fully saturated liquid.
     
  12. OP
    haidut

    haidut Member

    Joined:
    Mar 18, 2013
    Messages:
    11,162
    Gender:
    Male
    Location:
    USA / Europe
    Yep, and it will probably replace Ritanserin as it does not seem to generate much interest. We may keep it (ritanserin) as a specialty item.
     
  13. Blossom

    Blossom Member

    Joined:
    Nov 23, 2013
    Messages:
    5,159
    Gender:
    Female
    Would this replace progesterone for female rats or should they stay on their normal progesterone dose and use this as well?
     
  14. BastiFuntasty

    BastiFuntasty Member

    Joined:
    Jun 9, 2015
    Messages:
    220
    Gender:
    Male
    Sounds pretty cool, great work Haidut :thumbup
     
  15. OP
    haidut

    haidut Member

    Joined:
    Mar 18, 2013
    Messages:
    11,162
    Gender:
    Male
    Location:
    USA / Europe
    That was one of the goals - have a progestogen that has all good properties of progesterone (it and allopregnanolone seem to be the actual neurosteroids that give progesterone its good name), in much lower doses, and none of its negatives (i.e. precursor to cortisol and estrogen).
    The human equivalent dose (HED) of 0.3mg/kg was enough to lower estrogen receptor levels by ~75% and prolactin release by ~70%. You'd need about 2mg/kg human dose of progesterone to achieve the same, assuming all of that progesterone gets absorbed and delivered to the cell. As Ray said, the lipophilicity of the compound matters for cell access, and has recommended pentoxifylline over to caffeine for that reason - i.e. it is more fat soluble. This where 5α-DHP shines again - it is much more lipophilic than progesterone. In a solvent like DMSO it would have been an absolute gem but even in tocopherols it should be quite extraordinary.
    So yes, I think it should be able to replace regular progesterone for both women and men who use it.
    Of course, just my 2c and YMMV.
     
  16. X3CyO

    X3CyO Member

    Joined:
    Sep 19, 2016
    Messages:
    226
    Gender:
    Male
    Location:
    Erf
    So whats the catch? Just more calories and nutrients needed? And if so, how much faster is metabolism gonna be?
     
  17. Blossom

    Blossom Member

    Joined:
    Nov 23, 2013
    Messages:
    5,159
    Gender:
    Female
    Awesome. Thank you.
     
  18. TubZy

    TubZy Member

    Joined:
    Sep 30, 2016
    Messages:
    1,600
    Gender:
    Male
    Location:
    USA
    This is right down my alley...ordering now, thank you for no dmso
     
  19. Laurence

    Laurence Member

    Joined:
    Aug 9, 2016
    Messages:
    10
    Gender:
    Male
  20. OP
    haidut

    haidut Member

    Joined:
    Mar 18, 2013
    Messages:
    11,162
    Gender:
    Male
    Location:
    USA / Europe
Loading...