haidut

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Finally! Some common sense is emerging from the medical profession. For one, it points the finger straight at estrogen as a possible cause of autism. And not just estradiol, which the medical profession considers the only estrogen of note, but all 3 of them (estrone, estradiol, estriol). So, all the talk about estrone/estriol being weak and benign flies out the window. At least as far as fetal health is concerned. Also, this is one of only maybe 2 or 3 studies that I have seen over the last 17 years that cautioned against thinking of estrogen as a "female" hormone. As the study said, estrogen has many roles and one of them is masculinizing the brains of male fetuses. I would have also added "a major stress hormone" to the list of roles, but I suspect even a renowned public figure such as Prof. Baron-Cohen is concerned about keeping his job, and as such avoids making such shocking statements :):
Anyways, the cat is out of the bag - (prenatal) stress causes autism. Why? Well, at this point, we have studies linking high serotonin, low allopregnanolone, low GABA, endocrine disruptors (BPA, BPS, etc), endotoxin (LPS), high adrenaline, etc during pregnancy to the development of autism in the child. If you look at this list of possible autism causes, they are ALL basically symptoms of chronic maternal stress and/or low metabolism. As such, we it seems plausible to say that autism is simply the neurological manifestation of maternal stress inhibiting oxidative metabolism. The study authors even propose a mechanism through which estrogen causes may cause autism - disruption of the GABA system in the brain. More specifically, estrogen acts as a functional GABA antagonist, which matches quite well with the other studies mentioned above that found decreases allopregnanolone levels (and thus lower GABA activity) in autistic children. This suggests that autism is a form of chronic brain excitotoxicity driven by deficiency of GABA signalling. And if chronic stress alone was not enough, the potent environmental (xeno) estrogens such as BPA, BPS, soy isoflavones, resveratrol, birth control (BC) pills, etc are all adding to the estrogenic burden. As a matter of fact, about one third of women of reproductive age use BC pills on an ongoing basis, with usage often spanning decades. No wonder autism rates keep increasing, we are all bathing in estrogen!
There is some good news. It just so happens that progesterone addresses most of the possible causes listed above - i.e. inhibits TPH and thus serotonin synthesis, increases allopregnanolone levels, blocks the effects of BPA/BPS on estrogen and thyroid receptors and likely accelerates the elimination of such disruptors, binds/deactivates endotoxin and blocks TLR4, opposes adrenaline by increasing noradrenaline and of course it has a systemic pro-metabolic effects. Considering the rapidly rising rates/risk of (pre)eclampsia for all women, using supplemental progesterone is probably one of the most protective/beneficial things a mother-to-be can do. There should be no reason a doctor would deny progesterone to a pregnant woman, but some may try to push the synthetic progestins instead of bioidentical progesterone. Those progestins are poison! Most of them are estrogenic and androgenic, and despite their activity on the progesterone receptor cannot be compared to bioidentical progesterone. So, if a woman is talking to her doctor about progesterone I would be VERY careful that he/she does not do a bait-and-switch and prescribe a synthetic progestin instead by claiming that it is the "same as progesterone, only better".

Foetal oestrogens and autism | Molecular Psychiatry
https://medicalxpress.com/news/2019-07-high-estrogen-womb-linked-autism.html
Boys who develop autism 'may have been exposed to higher levels of female hormones in the womb'

"...Boys who develop autism may have been exposed to higher levels of ‘female’ hormones in the womb, suggests a new study. Cambridge University researchers found high levels of oestrogen had a bigger impact than the male hormone testosterone. The research team concluded that “oestrogenic excess is a characteristic of autism” in a paper published in the journal Molecular Psychiatry. Three out of four oestrogens analysed in the study were linked with autism – with oestradiol levels being the “most significant predictor”.

High levels of prenatal oestradiol contribute to a greater degree to autism likelihood than other prenatal sex steroids, including testosterone. “We conclude that prenatal oestrogenic excess is a characteristic of autism and may interact with genetic predisposition to affect neurodevelopment.” He warned the findings should not be used to screen for autism, adding: “We are interested in understanding autism, not preventing it."

"...Study co-author Alex Tsompanidis, a PhD student, said: “These elevated hormones could be coming from the mother, the baby or the placenta. “Our next step should be to study all these possible sources and how they interact during pregnancy.” He said despite oestrogen being thought of as a ‘feminising hormone’, in the womb it also has effects on brain growth and even ‘masculinises’ the brain in many mammals."

“This study reports the first evidence that elevated levels of prenatal amniotic oestradiol, oestriol and oestrone are each associated with autism, with oestradiol levels being the most significant predictor of autism likelihood in univariate logistic regression models. “We found that oestradiol had the strongest positive effect size on autism likelihood, followed by oestrone, oestriol and progesterone."

Oestrogen signalling could thus be a significant modulator of neuronal inhibition, particularly during early brain development and the critical period of cortical plasticity, which is heavily reliant on the GABAergic system. “We could not test whether prenatal oestrogens were associated with autism likelihood in females as there were too few diagnosed women in the HBC in this time window. We plan to test this by expanding the time window. Thus, at present, our findings only generalise to males."
 

haidut

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Btw, apparently estrogen's role as a stress hormone is well known among endocrinologists and I will be posting some additional threads on that soon. Why is this not more widely publicized and relayed to pregnant women is quite a mystery to me. My guess is that the pharma industry is trying to subvert the findings of the WHI study and bring estrogen back as therapy, even in pregnant women. Quite a few "opinions" have been written lately raising doubt about the WHI findings, and sales of estrogen have been rising over the last 5 years after an initial sharp drop around 2010 when the main WHI findings were announced.
 

lampofred

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If you look at Table 2, the study shows that progesterone is also elevated (but less than estrogen) in autistic children.

Vitamin D deficiency might be the cause behind that. I read a study a few weeks ago saying that supplementing vitamin D decreases estrogen strongly, decreases progesterone moderately, and increases testosterone, which aligns with the results of the study.

I think it is definitely plausible that the drastic decline in sunlight exposure and increase in blue light exposure via screens (which has the opposite of effect of sunlight exposure, making your body think it's winter instead of summer) is playing a role in the drastic increase in autism incidence in recent decades.

Going to email the authors and ask them if they measured Vitamin D levels.
 
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haidut

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If you look at Table 2, the study shows that progesterone is also elevated (but less than estrogen) in autistic children.

Vitamin D deficiency might be the cause behind that. I read a study a few weeks ago saying that supplementing vitamin D decreases estrogen strongly, decreases progesterone moderately, and increases testosterone, which aligns with the results of the study.

I think it is definitely plausible that the drastic decline in sunlight exposure and increase in blue light exposure via screens (which has the opposite of effect of sunlight exposure, making your body think it's winter instead of summer) is playing a role in the drastic increase in autism incidence in recent decades.

Going to email the authors and ask them if they measured Vitamin D levels.

Yeah, I saw that progesterone is also associated but if you read the actual study they make no secret of the fact they think estrogen is the most likely culprit. If you hear from them on vitamin D please post here. I wonder if we can find charts showing increase in vitamin D deficiency rates over the last few decades and whether those overlap well with the increasing autism rates...
 

Terma

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I would expect it to depend on the duration of the estrogen surge:
https://sci-hub.tw/10.1016/s0006-3223(03)00236-1
BDNF mRNA levels in the dentate gyrus and the medial prefrontal cortex were decreased during estrus, when estradiol levels are highest. Acute estradiol treatment decreased hippocampal BDNF mRNA in acutely OVX rats, but neither acute nor chronic estradiol had effect in chronically OVX rats. Estradiol pretreatment reduced the 5-HT2A receptor-mediated cortical upregulation in BDNF mRNA and did not effect the stress-induced down-regulation of BDNF mRNA in the dentate gyrus.
In male rats, restraint stress suppresses BDNF mRNA in the hippocampal DG and up-regulates it in the neocortex, in part through activation of 5-HT2A receptors (Vaidya et al 1997, 1999). Consistently, an acute increase in brain 5-HT suppresses BDNF mRNA in the DG while increasing it in the cortex (Zetterstrom et al 1999).
Chronic (2 weeks) estradiol treatment did not affect BDNF mRNA expression in the acute OVX rats. Others have reported that a longer (5 to 25 weeks) estradiol treatment of acute or short-term OVX rats increases BDNF mRNA in the hippocampus (Singh et al 1995; Berchtold et al 2001) and the olfactory bulb and decreases it in the cingulate cortex (Jezierski and Sohrabji 2000). Several studies now suggest that the short- and long-term estradiol treatments have opposite effects on BDNF regulation and likely underlie different adaptive neuronal changes and behavioral responses. Short-term (1 to 2 days) estradiol administration or its pulsatile surge during the estrous cycle down-regulates BDNFhttps://raypeatforum.com/community/tags/estradiol/ mRNA and protein in the hippocampus (this study; Gibbs 1998; Murphy et al 1998b), while long-term (more then 5 weeks) treatment results in increased BDNF mRNA (Singh et al 1995; Berchtold et al 2001). The duration of the estradiol treatment also affects differentially other aspects of neuronal excitability, plasticity, and behavior. The ini-tial estradiol-induced suppression of the inhibitory input onto the CA1 principal cells in the hippocampus is restored over a couple of days (Rudick and Woolley 2001). In aged rats, short-term estradiol treatment increases the DG granular cell dendritic spine density, whereas long-term treatment results in a decrease (Miranda et al 1999). The performance in some memory tests in rats could be worsened with short-term estradiol administration and improved with chronic treatment (Luine et al 1998; Galea et al 2001a).
In aged rats, the increase in the dendritic spine density with the short-term estradiol treatment was lost with the long-term treatment (Miranda et al 1999). This finding is in parallel to a recent double blind, placebo-controlled multicenter trial in Alzheimer’s disease patients, where the initial beneficial effects of estradiol replacement were reversed with long-term treat- ment (Mulnard et al 2000).
https://sci-hub.tw/10.1016/s0006-3223(03)00236-1
And then you have to factor in its effects on the cholinergic system.

[Edit: I removed the paragraph here because one of my interpretation errors will end up confusing everyone; another day; the point is that estrogen is meant to be pulsed]
 
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Ponce

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It’s strange that progesterone is potentially be causing autism when we know that it’s the only indispensable hormone for maintaining pregnancy. So certainly, the authors of the study may have forget an important factor in increase progesterone, or they may have simply distorted the result that shows that progesterone neonatal can increase probabilities to induce autism in the new-born child. Especially when we know the name of the great teacher who did the study
 

Yggr

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In this context of pregnancy, what does masculinizing the brain mean? Personally I find it hard to decipher why estrogen does this. What is a masculinized brain?
 

Aries

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In this context of pregnancy, what does masculinizing the brain mean? Personally I find it hard to decipher why estrogen does this. What is a masculinized brain?
The evidence is from animal studies and the proposed mechanism is mast cell activation by estrogen.

For
On Estrogenic Masculinization of the Human Brain and Behavior - PubMed
Against
Is Human Brain Masculinization Estrogen Receptor-Mediated? Reply to Luoto and Rantala - PubMed
Rats
Mast Cells in the Developing Brain Determine Adult Sexual Behavior - PubMed
 
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