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Estrogen Causes Epilepsy/seizures; Aromatase Inhibitors Are Viable Treatment

Discussion in 'Scientific Studies' started by haidut, May 12, 2016.

  1. haidut

    haidut Member

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    In perhaps what is one of the most striking and open confirmations of Ray's views, this study finally acknowledges what the man has been saying for years. Estrogen is a major cause (and maybe even THE cause) of epilepsy and its associated seizures, and inhibiting estrogen synthesis may be a viable treatment for the condition and other conditions associated with seizures. The study used aromatase inhibitors (AI) but the Peatrian approach of progesterone, vitamin E, vitamin K, vitamin A, emodin, etc may be a much safer and even more effective method considering that substances like progesterone and vitamin E are BOTH estrogen "receptor" antagonists and aromatase inhibitors. So, taking them provides the effects of a drug combination consisting of say fadrozole / letrozole / anastrozole (AI) and fulvestrant (ER antagonist) without most of the side effects these drugs have. Anti-histamine and anti-cholinergic drugs also block estrogen's effects, so cyproheptadine and/or Benadryl might also be an option.
    What is even more interesting is that seizures stimulate estrogen synthesis and establish a positive feedback loop, which is similar to the positive feedback loop observed between estrogen and cortisol.
    Finally, the study open discusses the possibility that stress, with its known effects on aromatase and estrogen synthesis, has a primary role in the develoopment and pathology of epilepsy and seizure disorders in general.
    Btw, it makes me sick to even think that a current commonly prescribe therapy for seizures is...estrogen in the form of birth control pills.

    Acute inhibition of neurosteroid estrogen synthesis suppresses status epilepticus in an animal model

    "...Status epilepticus (SE) is a common neurological emergency for which new treatments are needed. In vitro studies suggest a novel approach to controlling seizures in SE: acute inhibition of estrogen synthesis in the brain. Here, we show in rats that systemic administration of an aromatase (estrogen synthase) inhibitor after seizure onset strongly suppresses both electrographic and behavioral seizures induced by kainic acid (KA). We found that KA-induced SE stimulates synthesis of estradiol (E2) in the hippocampus, a brain region commonly involved in seizures and where E2 is known to acutely promote neural activity. Hippocampal E2 levels were higher in rats experiencing more severe seizures. Consistent with a seizure-promoting effect of hippocampal estrogen synthesis, intra-hippocampal aromatase inhibition also suppressed seizures. These results reveal neurosteroid estrogen synthesis as a previously unknown factor in the escalation of seizures and suggest that acute administration of aromatase inhibitors may be an effective treatment for SE."

    "...These results reveal neurosteroid estrogen synthesis as a previously unknown factor in the progressive escalation of seizures in an animal model of SE and provide the first in vivo evidence of a functional role for neurosteroid estrogens in the hippocampus. We found that systemic administration of an aromatase inhibitor after the onset of KA seizures strongly suppressed electrographic and behavioral seizure activity, in both sexes, without additional interventions. Microdialysis showed that seizures stimulate de novo synthesis of estrogens in the hippocampus and that animals with more severe seizures began with or reached higher levels of E2 in the hippocampus. Because E2 is known to acutely promote hippocampal neural activity, this suggested that E2 synthesized in the hippocampus might be seizure-promoting. Consistent with this, infusion of an aromatase inhibitor specifically into the hippocampus also suppressed both electrographic and behavioral seizures. These results support the idea of a positive feedback loop between seizure activity and neurosteroid estrogens in which seizures stimulate estrogen synthesis in the brain, which then acutely promotes neural activity, contributing to further seizure activity. Breaking this cycle with aromatase inhibitor therapy may be a novel approach to clinical control of SE."

    "...That we detected a range of basal E2 concentrations suggests that factors in addition to seizures may regulate aromatase activity in the hippocampus. For example, studies in the avian brain indicate that stress regulates enzymes involved in E2 metabolism (Soma et al., 2004; Dickens et al., 2011). Given our observation that high basal E2 is associated with more severe seizures in response to KA, understanding how basal E2 levels in the hippocampus are influenced by stress or other experience may have important implications for understanding the role of environmental factors in modulating seizure susceptibility and/or severity."
     
  2. ecstatichamster

    ecstatichamster Member

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    Great find. Thanks!
     
  3. HDD

    HDD Member

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    Thank you for posting this. A family member recently had a seizure premenstrually. I have sent her progesterone and am putting together information for her. Your timely post will now be included.
     
  4. PakPik

    PakPik Member

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    I'm grateful that you share this info, very important for people suffering from chronic seizures/seizure like disorders. This reminds me of Peat's explanation:

    "And the estrogen in a healthy person… when a nerve is stressed, the activation of these enzymes which are normally inactive in a nerve… stress activates the production of a little estrogen which sends out signals to the surrounding cells to cause them to produce pregnenolone, progesterone, allopregnanolone and a whole range of protective nerve steroids...but if you don’t have the energy, you get stuck in producing just the estrogen, which keeps things excited and stressed."Diabetes II And How To Restore And Protect Nerves, KMUD, 2014

    The seizure issue also has a mast cell connection, and unsurprisignly, estrogen is a known mast cell activator, whereas progesterone is a stabilizer:
    "More importantly, mast cells have been implicated in the pathogenesis of seizures. One study using a mouse model showed that the non-allergic mast cell trigger compound 48/80 significantly increased the rate of seizures in mice induced by electric shock, and this effect was eliminated in mast cell-depleted mice"
    http://www.ncbi.nlm.nih.gov/pubmed/22129087/

    "In addition, mast cells are also involved in neuroinflammatory conditions (3). Many such conditions are exacerbated by estrogens (4-7) and/or are associated with a state of progesterone deficiency"
    "The biochemical and ultrastructural findings presented indicate that progesterone can inhibit
    rat mast cell secretion
    . The inhibitory effect of progesterone appears to be unique as it is not apparent with other structurally similar compounds, such as cholesterol. Testosterone also inhibited secretion at similar concentrations, while β-17 estradiol augmented mast cell secretion"
    Progesterone inhibits mast cell secretion. - PubMed - NCBI
     
  5. CoolTweetPete

    CoolTweetPete Member

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    Hmm, I'm trying to think of this as it relates to ketogenic diets that I've heard are good for epileptics. I have a hard time imagining they are eating mostly saturated fats and strictly avoiding PUFA (estrogenic). From epilepsy.com,

    "The ketogenic diet is a special high-fat, low-carbohydrate diet that helps to control seizures in some people with epilepsy. It is prescribed by a physician and carefully monitored by a dietitian. It is stricter than the modified Atkins diet, requiring careful measurements of calories, fluids, and proteins."

    Maybe it has to do with the removal of poor carbohydrate sources like grains.
     
  6. Lilac

    Lilac Member

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    My 86-year-old mother had a horrible winter sickness this year, including migraine with hallucinations. A seizure of some kind seemed to be involved. I finally e-mailed Dr. Peat, and he recommended 1/8 teaspoon of progesterone (while also suspecting hypothyroidism). We had been doing the standard dose every 10 minutes. The bigger dose was even more helpful. Also, the progesterone was the only thing that helped that did not produce side effects. I'd like to add that Peat's advice provided more real relief than about 10—yes, 10—different M.D.'s.
     
  7. charlie

    charlie The Law & Order Admin

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    :rightagain
     
  8. johnwester130

    johnwester130 Member

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    would calcium d-glucurate be a useful solution ?
     
  9. treelady

    treelady Member

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    I've had epilepsy for the last 5 years. I just wanted to add that, in my case anyway, in addition to low progesterone, low thyroid is also involved. So far I'm not cured but T3 has helped.
     
  10. aussiedownunder

    aussiedownunder Member

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    Thank you for this. My sister seems to fit this picture as she developed epilepsy in her forties and has seizures when she is stressed.
     
  11. agnostic

    agnostic Member

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    Here's another great study that was just published on pubmed today showing that an aromatase inhibitor protects against seizures. Interestingly, they also tested finasteride and could show that it attenuated the positive effects:

     
  12. OP
    haidut

    haidut Member

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    Thanks. The negative effects of finasteride are likely due to lowering synthesis of allopregnanolone, which is the endogenous anti-seizure steroids together with progesterone. Allopregnanolone is apparently more important in respect to seizure than progesterone.
     
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