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Androgen stimulates transcription and replication of XMRV

Discussion in 'XMRV Research and Replication Studies' started by omerbasket, Feb 12, 2010.

  1. Cloud

    Cloud Guest

    I'm really amazed and yet thankful that Dr Judy would respond to emails on clinical questions because it could easily become overwhelming with all the desperate pwc's out here. But since she does seem to be ok with it, I think it would be great to ask her in one email about all of the endocrine contribution to xmrv replication, rather than just one hormone. I would ask how significant a contribution cortisol, androgens, estrogen, progesterone, all of them make on xmrv replication....and if supplementing these hormones for those who need them is a bad idea. Many of us are supplementing these hormones.

    It seems more research is needed to answer these questions adequately because I read that xmrv likes the tissue with the highest sex hormone receptors, then I read that it loves the stress hormones, then I read that it lives predominantly in the immune cells. Seems we have a ways to go with understanding this issue better.....but maybe Dr Judy can clarify this some for us.
  2. Rrrr

    Rrrr Senior Member

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    judy has said many times that cortisol, estrogen and androgens all stimulate xmrv.
  3. Rrrr

    Rrrr Senior Member

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    cloud, if you can craft about 3 questions, in bullet form, i'll send them to her. or you can!

    i want to tell her about my results with spironolactone, so i could send our questions in that email, too. just let me know.

    just let me know.
  4. Cloud

    Cloud Guest

    Cool, thank you Rrr, I would only have 2 questions to add....

    -If cortisol increases xmrv replication, would hydrocortisone supplementation be a concern even if it's treating a deficiency?

    -The same question on Thyroid supplementation (since it pushes the adrenals) as well please.
  5. Rrrr

    Rrrr Senior Member

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    Actually, I was hoping I might convince you to write up ALL the questions that have come up over the past few days (this is my not so sneaky way of saying I can't do it), not just the two new ones you added, but all of them, from you and everyone, so that I could have all the questions in one email, and not have to re-read thru the posts to find out what hte questions are. And I was hoping we could not have more than 3, so as not to overwhelm judy m. Can you do this by chance? If not, maybe someone else can. I know it is only a 10 min task, but I can't do it right now.

    warmly,
    rrrr
  6. Rrrr

    Rrrr Senior Member

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    update: i continue to do better than usual on this med (spironolactone). today i went for a real walk: 15 minutes. unusual for me. i felt like i could even run! (i didn't tho.) then in the p.m. i lifted small wrist weights (5 lbs each) with out feeling like it was taxing. unusual for me.

    and i have not been bedridden in a full week. also unusual for me.

    i don't know if this is all due to the spironolactone or some other variable. there are always at least 5 variables in my life at any given time, things that could be making me better or worse.

    but this improvement seems pretty correlated to the spironolactone.

    i wish someone else would hurry up and try it and see how they do with it!

    i'm now taking 25 mg in the a.m. and that is all.

    rrrr
  7. Tembo

    Tembo Australia

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    Thats just so wonderful Rrrr:) Not having to go to bed for a week must feel like a holiday! I hope it lasts for you. Im booking an appt with my doc and am going to ask her about it.

    I think Clouds idea of one email to Judy is a good but Im afraid I have no brain power for it - its hard enough just remembering how to turn my laptop on somedays. Any else up for the challenge?

    is Judys email address on the WPI website?
  8. Rrrr

    Rrrr Senior Member

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    if no one volunteers, i'll try to do it this week...

    meanwhile, i started a new thread dedicated just to spironolactone. http://www.forums.aboutmecfs.org/sh...helping-me-spironolactone&p=101937#post101937

    with that thread, i hope to convince others to try it and see if they get any good results. keep me posted, tembo! and remember, i do have high androgens and testosterone. so that could be why i am getting good results.

    judy's email is judym@wpinstitute.org

    i'm happy to send her the email, i was just wondering if someone could compile the hormone related questions already stated on this thread... but seems we are all too sick or maxed out.
  9. Rrrr

    Rrrr Senior Member

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    okay, i'm going to start compiling the questions. here is a start:

    Due to the fact that XMRV is stimulated by cortisol, estrogen and androgens:

    1. Is it true that XMRV prefers progesterone to replicate and that is why CFIDS and FMS affects more women than men?

    2. Should people not take any estrogen or progestrone supplements, including post menopausal women? (e.g. estradiol to keep from having hot flashes, progesterone IUD)

    3. If cortisol increases xmrv replication, would meds that directly or indirectly stimulate Cortisol production be good or bad for us, like hydrocortisone supplementation, or licorice root extract? Would these be a concern even if it's treating a deficiency?

    4. The same question on Thyroid supplementation (since it pushes the adrenals) as well please.

    5. wondering if it is NOT a good idea to take supplemental DHEA even though my androgen levels are undetectable?

    6. Can men who are XMRV+ and who have signs of neuro immune disease (CFS/ME) have their progesterone measured to compare their progesterone levels with healthy XMRV- controls?

    7. Why are people with CFS/ME reporting lower than normal cortisol levels, and/or abnormal ACTH stimulation tests? Where does the cortisol go? Does XMRV 'use' it? Or does XMRV impair adrenal gland function through organ (adrenal gland) infection?

    8. What are the base line levels of DHEA and DHEA-S in XMRV+ males and females, compared to healthy controls?

    9. but does xmrv eat your hormones? Or does your body downregulate it for protection?

    10. Can you comment on this quote: "Perhaps its the cyclical change in progesterone levels in females that provokes XMRV replication, whereas in males testosterone levels are mostly static? Or perhaps the relationship is more specific than "androgen stimulates XMRV" - perhaps its a specific type of Androgen, or its dependent on receptor expression which is different between the sexes. Like everything with this disease, hormone relationship to XMRV is likely way more complicated than "we have more or less of this or that androgen"

    11. Can you comment on this quote: "I'm a gradual onset male who got servery worse upon starting testosterone supplementation in hopes of giving me energy. It seemed reasonable at the time. I'm pretty sure that was the trigger to my decline and not anything else. Unfortunately stopping the testosterone hasn't helped which if it caused XMRV to transcribe and replicate." And this quote, "I can say that my doctor put me on hydrocortisone and testosterone last year for several months and I'm more disabled than before, thank you doc... I stopped it all few months ago but I'm not back to where I was, sadly, I'm quite sure the hormones did that"

    12. good scientific summary of xmrv's ability to mimic progesterone found here http://cfidsresearch.blogspot.com/2009/11/modus-operandi-of-xmrv-pt1.html: "So, as a molecular biologist, it leaves me to theorize that if this virus can mimic progesterone, it can create a state that allows the immune system to ignore the virus, very much like it ignores a developing fetus - scary isn't it? Observations reveal that high rates of estrogen, or high rates of testosterone in the absence of progesterone tend to favor the growth of XMRV - progesterone inhibits the formation of DHT. It seems to indicate that succeptibility to ME/CFS is strongly hormone driven, and why ME/CFS and FM are strongly female prevalent." QUESTION: Is this molecular biologist's thinking on track or off track?
  10. gu3vara

    gu3vara Senior Member

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    I can say that my doctor put me on hydrocortisone and testosterone last year for several months and I'm more disabled than before, thank you doc...

    I stopped it all few months ago but I'm not back to where I was, sadly, I'm quite sure the hormones did that
  11. Cloud

    Cloud Guest

    Thank Rrr, good questions, laid out well.

    It seems to me that a person taking hormone supplementation due to deficiencies would only be supporting their system to better fight pathogens such as xmrv because the supplementation brings the hormone levels up to normal. Of course, pushing the levels above normal, would be detrimental. Cortisol for example, is immune supportive at low amounts, but becomes immune suppressive at higher amounts. But then what it does to xmrv may be yet another story. This is a very tricky situation and we do need to know more because I have been down this road before with feeling that corticosteroid supplementation caused a relapse (one of my worst relapses). I also know that I feel so much better and like my system is working better with T3 and cortisol supplementation. What to do? I'm glad you added "even when treating a deficiency" onto #3.
  12. Rrrr

    Rrrr Senior Member

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    I'm going thru the whole thread and the questions list will expand. unfortunately. so check back in on it later, or i'll repost on a new post the new list of questions.
  13. guest

    guest Guest

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    One question I have been asking myself for a long time is, why XMRV causes disease when it has so low replication numbers and can only be found in very few cells?
  14. xrayspex

    xrayspex Senior Member

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    u.s.a.
    re:spironolactone

    I am very intrigued about this substance
    is it hard to get it?

    it seems like since I have stopped getting my moon I dont have as many ups and downs, and when I used to get it my spine turned into a noodle for a couple days, bedridden.
    I used to take a little progesterone for pms but when i tried it again since in menopause it flared up pain so dont use it, tried other bioidentical hormones and they all made me feel like crap
  15. xrayspex

    xrayspex Senior Member

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    hmmm but this doesnt sound good on wikipedia:

    Adverse effects and interactions

    Spironolactone is associated with an increased risk of bleeding from the stomach and duodenum, but a causal relationship between the two has not been established.[3] Because it also affects androgen receptors and other steroid receptors, it can cause gynecomastia, menstrual irregularities and testicular atrophy. Other side-effects include ataxia, erectile dysfunction, drowsiness, and rashes. A carcinogenic effect has been demonstrated in rats, see below. Spironolactone has been shown to be immunosuppressive in the treatment of sarcoidosis.[4]

    Spironolactone often increases serum potassium levels and can cause hyperkalemia, a very serious condition. Therefore, it is recommended that people using this drug avoid potassium supplements and salt substitutes containing potassium.[5] Doctors usually recommend periodic screening of serum potassium levels and some patients may be advised to limit dietary consumption of potassium.


    Research has also shown that spironolactone can interfere with the effectiveness of antidepressant treatment. The drug is actually (among its other receptor interactions) a mineralocorticoid (MR) antagonist, and has been found to reduce the effectiveness of antidepressant drugs in the treatment of major depression, it is presumed by interfering with normalization of the hypothalamic-pituitary-adrenal axis in patients receiving antidepressant therapy.[6]
    [edit] Carcinogenicity

    Studies of spironolactone and the related compound potassium canrenoate (which, like spironolactone, metabolizes to canrenone) in rats for one- to two-year periods show an increase in carcinogenesis in the thyroid gland, testes, liver, breasts, and myelocytic leukocytes. Mammalian cells, depending on the presence of metabolic activation, show mixed results for mutagenicity in vitro.[7] Doses relative to body weight were 10 to 150 mg per kg, which is ten to 500 times higher than normal doses for treating humans. In light of this research, Sandoz has recommended that unnecessary use of spironolactone be avoided.
    [edit]
    ----------------------------
    ---------
    lots of good things listed too.

    sposed to have script? google shows easy to get internet, problem with that, quality assurance?
    http://www.inhousepharmacy.com/transgender/aldactone-t.html
  16. Rrrr

    Rrrr Senior Member

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    well, all i know is that i was on it for years and years, then stopped. got worse. and now i'm back on it and doing better. but good to read all those bad side effects! thanks for posting that!
  17. Cloud

    Cloud Guest

    Most drug information sources will list every possible side effect making it appear the side effects are worse than the symptom one is treating. And many times this is true with Allopathic medicine. But some medication information sources will fine tune the information a little better. For example, the Nursing drug handbooks list every possible side effect, but also details which are more common, and which can be most harmful. PDR's used to laid out the same. This can help with weighing a drugs benefits against the possible hazards.
  18. dannybex

    dannybex Senior Member

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    Seattle
    Same here. Plus, everyone has these hormones, of course some more than others -- especially stress hormones -- but more 'healthy' people have XMRV than folks like us.

    So many questions...will probably take years to answer. :)
  19. liverock

    liverock Senior Member

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  20. ukxmrv

    ukxmrv Senior Member

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    I miss Dr Luckett's updates. Does anyone know what happened to him?

    (see above blogspot CFidsresearch)

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