Estrogênio possui propriedades claramente neurotóxicas
Estrogênio sem oposição da progesterona é tóxico sob diversos pontos de vista
[Imagem: kino-teatr.ru]
O simples uso de um estrógeno teve como efeito a destruição de 60% dos neurônios de uma determinada região do cérebro [A]. Claramente, uma neurotoxicidade de parte desse hormônio que cumpre um papel no estresse, o estrogênio.
O estudo acima foi realizado em animais, mas quando bem examinado, se mostra irrefutável quanto à toxicidade do estrogênio.
Os mesmos cientistas [A] testaram substâncias na tentativa de proteger os neurônios da ação nefasta do estrogênio. Observaram que o tratamento crônico com a vitamina E tem efeito protetor e que esse mesmo tratamento preveniu a instalação de cornificação persistente da vagina e ovário policístico, problemas que foram resultado da suplementação com aquele mesmo estrógeno.
O estudo é canadense, dos anos 1990 e, é in vivo, mas pelo que se saiba, não repercutiu nos protocolos médicos voltados para uma saga pela “reposição do estrogênio” nas mulheres menpausadas...
Segundo G Dinkov, que divulgou o estudo, a dose da vitamina E usada no experimento, traduzida no correspondente a humanos [HED] gira em torno de 200 UI, do mix de tocoferóis.
Outro estudo do mesmo grupo canadense de pesquisas [C], foi mais longe, mostrou a mesma destruição neuronal e também a seletividade do estrógeno naquele ataque neurotóxico.
E concluiu que “as evidências indicam que o efeito neurotóxico seletivo do estradiol nos neurônios hipotalâmicos beta-endorfínicos contribuem para a senescência reprodutiva, sugerindo que esteroides podem participar da disrrupção de funções biológicas” [C].
E um novo estudo [D] mostrou o estradiol não apenas destruindo neurônios mas engendrando, diretamente a síndrome do ovário policístico [D].
Neste caso, a persistente supressão dos opióides pelo estrogênio provocou um padrão mais inibido do LH no plasma “diante do qual os ovários respondem tornando-se anovulatórios ou policísticos” [D]. E concluem que aquela ação neurotóxica do estradiol pode contribuir para um sem número de desordens reprodutivas em humanos e animais [D].
A senescência do aparelho reprodutor feminino tem a ver com estrogênio em excesso [sem oposição da progesterona]. É o que conclui outro estudo [E], que defende a prevenção daqueles efeitos neuroendócrinos do estradiol – que podem levar a ciclos anovulatórios - com tratamento com antioxidantes. Em outro estudo [A] os autores defenderam o uso da vitamina E e sabemos, por R. Peat, que a progesterona e a recuperação da normalidade tireoidiana seriam ainda mais estratégicos.
Outros estudos também mostram que não é tanto a idade quanto a exposição repetida ao estradiol o que determina a senescência do aparelho reprodutivo da mulher [F].
Mas o fato é que a ação nefasta dos estrógenos, amplamente usados em mulheres menopausadas fica sob questão com pesquisas como essas.
Inequivocamente, elas revelam a neurotoxicidade do estrogênio, levantando o alerta sobre a contribuição do estrogênio, como tóxico neuronal, na gênese de doenças como Alzheimer ou demência.
GM Fontes. Brasília, 19-2-24
As informações aqui presentes não pretendem servir para uso diagnóstico, prescrição médica, tratamento, prevenção ou mitigação de qualquer doença humana. Não pretendem substituir a consulta ao profissional médico ou servir como recomendação para qualquer plano de tratamento. Trata-se de informações com fins estritamente educativos.
Referências _________
[A] DESJARDINS G C BEAUDET A SCHIPPER H M, 1992. Vitamin E protects hypothalamic beta-endorphin neurons from estradiol neurotoxicity. Endocrinology. 1992 Nov;131(5):2482-4. doi: 10.1210/endo.131.5.1425446. PMID: 1425446
DOI: 10.1210/endo.131.5.1425446 “Estradiol valerate (EV) treatment has been shown to result in the destruction of 60% of beta-endorphin neurons in the hypothalamic arcuate nucleus. Evidence suggests that the mechanism of EV-induced neurotoxicity involves the conversion of estradiol to catechol estrogen and subsequent oxidation to free radicals in local peroxidase-positive astrocytes. In this study, we examined whether treatment with the antioxidant, vitamin E, protects beta-endorphin neurons from the neurotoxic action of estradiol. Our results demonstrate that chronic vitamin E treatment prevents the decrement in hypothalamic beta-endorphin concentrations resulting from arcuate beta-endorphin cell loss, suggesting that the latter is mediated by free radicals. Vitamin E treatment also prevented the onset of persistent vaginal cornification and polycystic ovarian condition which have been shown to result from the EV-induced hypothalamic pathology”.
[B] https://raypeatforum.com/community/threads/estrogen-is-neurotoxic.5474/#post-245520
[C] DESJARDINS G C BRAWER J R, 1993. Estradiol is selectively neurotoxic to hypothalamic beta-endorphin neurons. Endocrinology. 1993 Jan;132(1):86-93. doi: 10.1210/endo.132.1.8093438. PMID: 8093438 DOI: 10.1210/endo.132.1.8093438 “The neurotoxic effects of estradiol on hypothalamic arcuate neurons were examined in a model of chronic estrogenization induced by means of a single injection of estradiol valerate (EV). Eight weeks after EV treatment, a 60% decrease in the total number of beta-endorphin-immunoreactive neurons was detected in the arcuate nucleus. In contrast, the numbers of neurotensin-, somatostatin-, and tyrosine hydroxylase-immunoreactive neurons were unchanged, suggesting that the effects of estradiol were selective for beta-endorphin neurons. Further evidence for the selectivity of estradiol's actions was provided by RIAs indicating decreases in hypothalamic beta-endorphin concentrations, but not in Metenkephalin or neuropeptide-Y concentrations. Cell counts performed in Nissl-stained material using unbiased stereological methods revealed a reduction in the total number of neurons in the EV-treated group compared to that in the controls. The estimated number of neurons lost (approximately 3500) corresponded precisely with the total number of beta-endorphin neurons lost (approximately 3600), as estimated using quantitative immunocytochemistry. These results confirm the selectivity of estradiol's effect on the beta-endorphin cell population and demonstrate that the observed decrease in beta-endorphin immunoreactivity reflects actual cell loss. The evidence indicates that the selective neurotoxic effect of estradiol on hypothalamic beta-endorphin neurons contributes to reproductive senescence, suggesting that steroids may participate in disruption of the biological functions that they normally facilitate”.
[D] BRAWER J R BEAUDET A DESJARDINS G C, 1993. Pathologic effect of estradiol on the hypothalamus. Biol Reprod. 1993 Oct;49(4):647-52. doi: 10.1095/biolreprod49.4.647. PMID: 8218628 DOI: 10.1095/biolreprod49.4.647 “Estradiol provides physiological signals to the brain throughout life that are indispensable for the development and regulation of reproductive function. In addition to its multiple physiological actions, we have shown that estradiol is also selectively cytotoxic to beta-endorphin neurons in the hypothalamic arcuate nucleus. The mechanism underlying this neurotoxic action appears to involve the conversion of estradiol to catechol estrogen and subsequent oxidation to o-semiquinone free radicals. The estradiol-induced loss of beta-endorphin neurons engenders a compensatory increment in mu opioid binding in the medial preoptic area rendering this region supersensitive to residual beta-endorphin or to other endogenous opioids. The consequent persistent opioid inhibition results in a cascade of neuroendocrine deficits that are ultimately expressed as a chronically attenuated plasma LH pattern to which the ovaries respond by becoming anovulatory and polycystic. This neurotoxic action of estradiol may contribute to a number of reproductive disorders in humans and in animals in which aberrant hypothalamic function is a major component”.
[E] DESJARDINS G C BEAUDET A MEANEY M J 1995. Estrogen-induced hypothalamic beta-endorphin neuron loss: a possible model of hypothalamic aging. Exp Gerontol. 1995 May-Aug;30(3-4):253-67. doi: 10.1016/0531-5565(94)00040-a. PMID: 7556506
DOI: 10.1016/0531-5565(94)00040-a “Over the course of normal aging, all female mammals with regular cycles display an irreversible arrest of cyclicity at mid-life. Males, in contrast, exhibit gametogenesis until death. Although it is widely accepted that exposure to estradiol throughout life contributes to reproductive aging, a unified hypothesis of the role of estradiol in reproductive senescence has yet to emerge. Recent evidence derived from a rodent model of chronic estradiol-mediated accelerated reproductive senescence now suggests such a hypothesis. It has been shown that chronic estradiol exposure results in the destruction of greater than 60% of all beta-endorphin neurons in the arcuate nucleus while leaving other neuronal populations spared. This loss of opioid neurons is prevented by treatment with antioxidants indicating that it results from estradiol-induced formation of free radicals. Furthermore, we have shown that this beta-endorphin cell loss is followed by a compensatory upregulation of mu opioid receptors in the vicinity of LHRH cell bodies. The increment in mu opioid receptors presumably renders the opioid target cells supersensitive to either residual beta-endorphin or other endogenous mu ligands, such as met-enkephalin, thus resulting in chronic opioid suppression of the pattern of LHRH release, and subsequently that of LH. Indeed, prevention of the neuroendocrine effects of estradiol by antioxidant treatment also prevents the cascade of neuroendocrine aberrations resulting in anovulatory acyclicity. The loss of beta-endorphin neurons along with the paradoxical opioid supersensitivity which ensues, provides a unifying framework in which to interpret the diverse features that characterize the reproductively senescent female”.
[F] HUNG A J STANBURY M G CHANABROUGH M, 2003. Estrogen, synaptic plasticity and hypothalamic reproductive aging. Exp Gerontol. 2003 Jan-Feb;38(1-2):53-9. doi: 10.1016/s0531-5565(02)00183-3. PMID: 12543261 DOI: 10.1016/s0531-5565(02)00183-3 “Unlike primates who undergo ovarian failure and loss of sex steroids at the end of reproduction, aging rodents undergo constant vaginal estrus followed by constant diestrus and finally anestrus, which indicates the absence of responsive ovarian follicles. The latter state is analogous to menopause in women. The timing of the appearance of constant estrus is determined by many factors including estrogen exposure in the brain during development and the number of times that the animal gets pregnant. The chief site of this reproductive aging in rat brains is the arcuate nucleus of the hypothalamus. The transition from normal cycles to constant estrus parallels the females' gradually decreased ability to respond to administered estradiol with a cycle of inhibition followed by disinhibition of gonadotrophin-releasing hormone. Evidence has accumulated indicating this to be due to a loss of the rat's ability to respond to markedly elevated estradiol with the usual arcuate nucleus neuro-glial plasticity that supports the estrogen-induced gonadotrophin surge (EIGS). Just as male rats are not capable of an EIGS, aged females loose this ability through repeated EIGS. Experiments indicate that in male rats the hypothalamic synaptology that develops as a result of exposure to testicular androgens in the perinatal period (brain sexual differentiation) is a result of conversion of testosterone from the testes to estrogen in the brain and is therefore due to early estrogen exposure. Aging females appear to reach a synaptology similar to males and constant estrus as a result of repeated exposure to ovarian estrogens during their reproductive careers. The relative role of aging and hormonal factors remains unclear. Morphological evidence is presented that indicates the above effects of estrogen involve changes in hypothalamic arcuate nucleus neurons and glia, including changes in the organization of perikaryal membranes as well as arcuate nucleus synaptology and the load of peroxidase in the astroglia. A possible role for free radicals (reactive oxygen species) in hypothalamic reproductive aging has been proposed. Such a mechanism is supported by evidence that the anti-oxidant vitamin E delays the onset of constant estrus and the accumulation of glial peroxidase in aging female rats. However, since the synaptology and peroxidase load in constant estrus females is independent of the age at which the constant estrus occurs, it appears that the role of (repeated) estradiol exposure is more deterministic of hypothalamic failure than is aging, per se”.
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