High Estrogen (Androgen Deficiency) Causes Low Vitamin D; DHT Is Therapeutic

Discussion in 'Scientific Studies' started by haidut, Jan 30, 2018.

  1. haidut

    haidut Member

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    I rarely stumble across studies like this one. Namely, showing in one single experiment both the detrimental effects of estrogen on one of the most important biomarkers of health (vitamin D), and the beneficial effects of a steroid long vilified/demonized by virtually everybody wearing a white coat.
    Low vitamin D levels are rampant in the Western population, with some estimates as high as 80% of people over the age of 25. While supplementation is commonly prescribed, people often find that even very high oral doses of vitamin D do not bring up blood levels. Peat told some people over email that excess fat weight is a factor in making vitamin D supplementation ineffective at raising blood levels. Well, excess fat is a major source of estrogen so the study makes even more sense now.
    The study below found that it is the relative deficiency of androgens that allows estrogen to rule unopposed and raise progesterone receptor (PR) levels, which results in lower vitamin D levels. Restoring androgen levels lowers PR (by opposing estrogen) and quickly improves vitamin D status. This matches well the recent study I posted claiming that androgen deficiency (and thus hypothyroidism) is perhaps the main cause of chronic diseases in males.
    Androgen Deficiency As The Main Cause Of Chronic Disease In Males
    It could very well be that low vitamin D levels are one of the main mechanisms of action through which androgen deficiency begets disease. While there are many ways to oppose excess estrogen, supplementation with progesterone or non-aromatizable steroids like DHT, androsterone, 5a-DHP and even allopregnanolone are among the most effective measures. Anyways, as the study below showed, administering the potent, non-aromatizable androgen DHT to androgen-deficient mice restores vitamin D level back to normal without any additional vitamin D supplementation. The HED for DHT was 0.15mg/kg for 5 days.
    Now, this study used a male mouse model. So, the question is what would work for females. Since progesterone is the main endogenous estrogen antagonist in females and since it also lower PR receptor density, I think progesterone supplementation is the obvious choice for females. Physiological doses of 10mg-15mg should be sufficient but some women with severe estrogen dominance or excess body fat may need higher doses. Speaking of progesterone, it should be useful for males too who do not have access to DHT, and a combination of progesterone + DHT may be even more effective.

    @Travis @Koveras @aguilaroja

    5α-dihydrotestosterone reduces renal Cyp24a1 expression via suppression of progesterone receptor
    "...Interestingly, the estrogen receptor α (Esr1) and progesterone receptor (Pgr) were clearly overexpressed in orchidectomized mice when compared to in sham-operated mice. In orchidectomized mice, DHT treatment significantly decreased Esr1 (Fig. 1C) or Pgr (Fig. 1D) mRNA levels in the kidney, when compared to in vehicle-treated or DHT-bicalutamide co-treated mice. This suggests that the DHT treatment induced androgen response transcripts and reduced estrogen response transcripts. It is generally accepted that estrogen induces PGR mRNA and protein levels, and there is evidence that ESR1 binds the estrogen receptor response element (ERE) of the PGR gene (Petz et al. 2004). Likewise, Pgr level is controlled by Ar through its competition with activated estrogen receptor on ERE site in the Pgr promoter (Peters et al. 2009)."

    "...To determine whether reduced 24-hydroxylase expression by DHT influences the levels of vitamin D3, we monitored plasma 25-hydroxyvitamin D3 in orchidectomized mice following treatment with DHT with and without bicalutamide for 5 days. We observed a significant increase in 25-hydroxyvitamin D3 in DHT-treated orchidectomized mice, as compared to that in corresponding vehicle-treated mice (Fig. 6A). In addition, co-treatment with bicalutamide almost completely blocked the DHT-stimulated increase in serum 25-hydroxyvitamin D3 (Fig. 6A), indicating that this stimulation must also be mediated by the androgen receptor, and this is linked with the previous results that show DHT regulating the expression of Pgr (Fig. 5E and H) regardless presence of estrogen receptor."

    "...To summarize, our results demonstrate that androgen (DHT) signaling controls 24-hydroxylase degradation by regulating Pgr expression at the transcriptional and translational levels (Fig. 6B). It is also supported by induction of vitamin D-related genes, including Calbindin-9k and Calbindin28k mRNA levels (Fig. 6C and D), suggesting testosterone significantly increased in active vitamin D-response gene. We also observed significant increase in Cyp27b1 mRNA levels in all orchidectomized mice when compared to sham-operated animal (Fig. 6E). This observation is consistent with the notion that an administration of estradiol to males increased Cyp27b1 activity (Pike et al. 1978, Lechner et al. 2006)."

    "...The results presented in our report indicate that androgen deficiency within renal function acts to enhance 24-hydroxylase expression and suppresses the actions of vitamin D, especially under conditions of limited supply of androgens. These findings uncover an important role for androgen in vitamin D homeostasis and suggest that therapeutic modulation of progesterone receptor may be used to treat vitamin D deficiency and related disorders."
     
  2. Dhair

    Dhair Member

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    There is something that I don't understand. Ray Peat always speaks as if low androgens must coincide with high estrogen. I have not found this to be the case, and neither have many men on this forum. Even when my prolactin, cortisol and estrogen were in the low reference range as indicated by labs, my testosterone was still very low. I understand that this still indicates low energy production, but I think things become confusing when we talk about high estrogen and low androgens essentially being the same condition. I have found that this lack of specificity can lead people down the wrong path.
     
  3. OP
    haidut

    haidut Member

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    Well, you have a valid point but the study looked at a very specific situation - i.e. high estrogen + low androgens induced by gonadectomy (a model of andropause). They did not look at how lowering estrogen/cortisol/prolactin would affect vitamin D levels, they tested the other side of the equation - i.e. what raising androgen levels would do. Also, while high estrogen and low androgens do tend to go hand in hand, lowering estrogen/cortisol/prolactin does not always resolve the issue, especially if there is central hypogonadism (i.e LH/FSH/GNRH issue, high TSH, etc). For most aging males though, high estrogen/cortisol and low androgens do go hand in hand and lowering estrogen/cortisol should help. If a younger person with hypogonadism does not benefit from lowering the stress mediators then I would look into those additional factors.
     
  4. Dhair

    Dhair Member

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    For me, LH, FSH, and TSH indicated no problems, so it is some issue in the HPA that cannot be located. I already sent you a PM about this so I won't discuss it further here, but I have been interested in the past couple studies you have posted on this topic precisely because they have to do with treating the problem with androgens directly, which you seem to rarely recommend. Do you think in the next few years that mainstream medicine will begin prescribing androgen therapy for conditions like CVD, MS, metabolic syndrome, etc? The study that you posted suggesting that androgen deficiency may be the case of chronic illness in males seemed really groundbreaking in that respect, especially considering the grear reluctance by most doctors to prescribe T/DHT for ANY purpose, mainly due to potential liability issues...
     
  5. raypeatclips

    raypeatclips Member

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    @haidut What do you think would happen to the other relationship? Where someone that struggles to raise vitamin D levels orally, manages to raise it with topical vitamin D, would DHT rise along with it?

    Edit: I think 3 minutes of forum searching has answered my question. Although I am not sure what would happen in low DHT, having good vitamin D status inhibiting the deactivation, whether it would just maintain a low DHT level?

    Vitamin D Inhibits The Deactivation Of Androgens
     
  6. OP
    haidut

    haidut Member

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    I think we are years away from medicine starting to use androgens or other steroids like progesterone as a mass-prescribed drug. The masses are nothing but testing ground for all kinds of poison. But well-off people already implement this on a daily basis. There are quite a few articles and several official studies showing that the vast majority of male celebrities use some kind of HRT. Unfortunately, they often combine it with HGH, hCG or another carcinogenic chemical so the benefits are compromised. But still, there is a reason why people with money are flocking to steroids and transfusions of blood from young people.
     
  7. OP
    haidut

    haidut Member

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    Vitamin D also potentiates the effects of androgen, as I posted in the main Calcirol thread. Other studies I posted in that thread show that the positive effect of androgens on muscle health depends to a degree on vitamin D. And finally, there is the thread on vitamin D and K potentially being useful as muscle anabolic agents due to their effects of raising osteocalcin. If osteocalcin rises, so does production of T in the gonads. The Wiki page on osteocalcin talks about that and some good references.
     
  8. Wagner83

    Wagner83 Member

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  9. OP
    haidut

    haidut Member

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    This is one of the people who reported very high DHT form using androsterone. I asked all of them to post their results.
     
  10. raypeatclips

    raypeatclips Member

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    Why do you think his vitamin D was so low despite his dht levels?
     
  11. OP
    haidut

    haidut Member

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    Don't know. If cholesterol levels are not optimal and it was really dark like he said, the maybe DHT on its own is not enough to restore vitamin D levels. The study I posted only looked at restoring vitamin D levels after the step labelled as "Previtamin D" on the picture in the Wiki page below.
    Cholecalciferol - Wikipedia

    So, if there is no sunlight and thus low previtamin D then DHT may not do much. The mice in the study were kept under optimal light so they had good UV exposure.
     
  12. Wagner83

    Wagner83 Member

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    Do you think a strong publicity will get it banned much quicker?
     
  13. raypeatclips

    raypeatclips Member

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    Interesting, thank you for the reply and it is refreshing seeing someone saying "don't know" and going through their thoughts, instead of trying to bull**** an answer!
     
  14. OP
    haidut

    haidut Member

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    Androsterone - probably not as it is protected similarly to DHEA by several laws, even though nothing is for sure with the FDA. But I don't have high hopes for 11-keto DHT staying around for long. The studies that guy (who studies 11-keto DHT) publishes already say it is a steroid that athletes would use and calls for developing a doping test for it. Once that happens, and possibly before that, 11-keto DHT is done.
     
  15. Madato

    Madato Member

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    Speaking from my n=1 experience:

    supplementing with 50mg Proviron a day + 3 applications of Andractim/day had my joints in pain in as little as a week, and my muscles looking completely flat.

    It must have driven my e2 too low.

    What amount of DHT do you have in mind for those therapeutic purposes with no ill-effects? (for people not on exogenous testosterone of course, otherwise it’s easy to include DHT in the protocole without low e2 sides)
     
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