O estrogênio cai na menopausa. Será verdadeɁ Você já ouviu falar da estrona [E1]Ɂ [PARTE 1 de 2]
O segredo revelado: não, o estrogênio não cai na menopausa, ele AUMENTA. A chave começa no entendimento do papel da estrona [E1], do estradiol [E2] e do estriol [E3].
[Moléculas de estriol, estradiol e estrona]
[Imagem: studbooks.net]
Para a medicina mainstream, a menopausa é uma época de deficiência de estrogênio. O pós-menopausa seria marcado, na narrativa oficial, pela queda nos estrógenos.
Obcecados em medir o estradiol [E2] plasmático, os especialistas facilmente caem no engodo de que menos estrogênio é a marca da menopausa, já que o estradiol plasmático, de fato, cai. E tocam a “repor” o estrogênio que “falta”.
Essa doutrina já se tornou obsoleta faz tempo. Mas continua de pé em consultórios.
Mas não, não se trata exatamente de uma falta. É puramente um problema de interpretação errada. E, no real, os estrógenos estão subindo na menopausa, e promovendo doenças. Tanto é assim que o quadro clínico da menopausa doentia é, todo ele, a cara do excesso de estrogênio.
Existem, de uma maneira geral, três tipos de estrógenos, o E1 [estrona], o E2 [estradiol] e o E3 [estriol].
Medir a estrona iria mostrar que, na menopausa, o estrogênio ganha uma tendência de crescimento não de queda.
E mais: a estrona [E1], especialmente a estrona-sulfato [E1S] na perspectiva de R. Peat, é um importante biomarcador de desenvolvimento tumoral [de próstata e de mama]. E, no entanto, raramente os doutores medem E1 e E1S.
E não levam em conta que, embora sendo um estrogênio fraco, a estrona se converte facilmente em estradiol [e em estriol] nos tecidos, fazendo com que a ação do estrogênio nos tecidos fique intensa apesar do estradiol estar baixo no plasma...
O estradiol que “falta” no plasma está abundante nos tecidos...
Mas, como explica, G Dinkov, por “alguma razão a indústria médica está obcecada com o estradiol, cujos níveis caem, sim, na menopausa”.
Expliquemos toda essa questão.
Mas antes examinemos a experiência abaixo.
O trabalho científico da Dra Sharon Parish, resumido na nota [A], destaca que a estrona é a maior fonte de estrogênio circulante.
Esse mesmo estudo, destacado por sugestão de G Dinkov, conclui, como foi dito acima, que a forma de medir estrogênio na mulher menopausada está errada e é por isso que a lenda continua pregando que o estrogênio decai na menopausa.
Nas próprias palavras dos cientistas, [A] “a mensagem fundamental das nossas descobertas é a de que estudos checando a associação entre estrógenos e doenças do envelhecimento em mulheres menopausadas devem medir estrona para que seus achados tenham algum significado”. Não deve se ocupar de medir estradiol, cujos valores não são mensuráveis ou apenas confundem.
Também confirmaram que uma mulher menopausada e que apresente mais peso [obesa] apresentará níveis mais elevados de estrógenos. Confirmando a relação adipócitos-aromatase-estrogênio.
Esse estudo examinou esteroides “sexuais” [estrona, estradiol, testosterona] de mais de seis mil mulheres pós-menopausa de ao menos 70 anos de idade. Excluíram mulheres em uso de qualquer esteroide, antiandrógeno, corticoide ou medicação para diabetes. Os cientistas entenderam que maiores níveis de testosterona em tese, diminuiriam risco para certas doenças [um tema para se deixar aqui em suspenso]. Observaram, por outro lado, que os níveis de estradiol [e DHT] eram abaixo da sensibilidade laboratorial.
Em mulheres mais idosas, a estrona se mostrou mais alta [mais ainda nas obesas, como foi mencionado]. E, como observaram testosterona mais alta em algumas mulheres, eles concluíram que “o estudo sugere que testosterona alta pode conferir uma vantagem de sobrevivência, particularmente considerando que entre as idades de 70 a 95 anos, certas mulheres mais velhas apresentavam níveis mais altos de testosterona naquela faixa etária”.
Mulheres mais velhas, níveis mais altos de testosterona, mas também níveis mais altos de estrona e declínio do DHEA, eis os achados importantes do estudo e os autores propõem que se reflita sobre tais descobertas [ A].
Não se pode esquecer, por outro lado – e conforme já destacado por R. Peat e Dinkov – que prolactina é maior na mulher pós-menopausada e seus níveis se correlacionam com a idade.
E que estrogênio é o condutor primário da secreção de prolactina, seguido por serotonina e cortisol. Portanto, aumento de prolactina aponta pra aumento de estrógeno.
Relembremos que o estudo [A] mostrou que mulheres obesas [idosas] apresentam os níveis mais elevados de estrona. Ora, como argumenta Dinkov, estrona [E1] é o estrógeno principalmente produzido por células gordas, adipócitos, ao passo que o estradiol [E2] é principalmente pelos ovários na mulher e testículos no homem.
Logo, a subida da estrona na pós-menopausa – passo a passo com a prolactina – são a precisa indicação que na menopausa os estrógenos não caem, ao contrário, se elevam.
[Continua na PARTE 2 de 2]
GM Fontes, 12-2-24
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] DAVIS, S, 2019. Higher testosterone level may confer ‘survival advantage’ in older women. August 21, 2019. Sex steroid levels, particularly levels of estrone and testosterone, vary widely among older women, with higher levels of testosterone possibly indicating lower risk for disease, according to findings published in The Journal of Clinical Endocrinology & Metabolism. Perspective from Sharon Parish, MD - “Estrone is the major source of circulating estrogen in older women and must be measured in any study seeking to determine the association between estrogens and health outcomes in older women,” Susan Davis, MBBS, FRACP, PhD, FAHMS, a professor in the School of Public Health and Preventive Medicine at Monash University, Australia, told Endocrine Today. “Consistent with previous studies, there are some older women with surprisingly high estrone levels, and this needs to be better understood. This study establishes that women beyond the age of 70 years have similar blood testosterone concentrations to those seen in healthy premenopausal women.”
In a cross-sectional study, Davis and colleagues analyzed sex steroid data from 6,392 women aged at least 70 years participating in ASPREE, a randomized controlled trial assessing the effect of low-dose aspirin vs. placebo on older adults without cardiovascular disease or impaired cognition at recruitment (98% European ancestry; mean BMI, 28 kg/m²). Researchers assessed sex steroids and sex hormone-binding globulin levels using liquid chromatography-tandem mass spectrometry.
“Until now, the available data have been limited by small sample sizes and/or the use of direct immunoassays, which lack sensitivity and specificity for the measurement of testosterone at the concentrations occurring in women, compared with the higher levels seen in men,” the researchers wrote.
Sex steroid levels, particularly levels of estrone and testosterone, vary widely among older women, with higher levels of testosterone possibly indicating lower risk for disease. A reference group to establish sex steroid, age-specific reference ranges (n = 5,326) excluded women using systemic or topical sex steroids, antiandrogen or glucocorticoid therapy or diabetes medications (mean age, 75 years).
Among the reference group population, median estrone level was 181.2 pmol/L, median testosterone level was 0.38 nmol/L, median dehydroepiandrosterone (DHEA) level was 2.6 nmol/L and median SHBG level was 41.6 nmol/L. Estradiol and dihydrotestosterone (DHT) levels were below the sensitivity of the assay method in 66.1% and 72.7% of women, respectively.
“There were a number of outliers for each steroid in each age group,” the researchers wrote. “We examined whether any of the measured variables (BMI, weight, waist circumference, smoking) and any reported medication use predicted extreme outliers for any of the steroids, but could not identify a common explanation for the outliers.”
Researchers found that women aged 80 to 84 years had estrone levels that were on average 9.2% higher vs. women aged 70 to 74 years (P = .001); women aged at least 85 years had estrone levels that were on average 11.7% higher vs. women aged 70 to 74 years (P = .01). When stratified by BMI, excess weight further influenced sex steroid levels, the researchers wrote, noting that older women with obesity had estrone levels that were on average 34.1% higher vs. women with normal weight (P < .001).
Similarly, women aged 80 to 84 years had testosterone levels that were on average 9.3% higher vs. women aged 70 to 74 years; that percentage rose to 11.3% for women aged at least 85 years (P = .02). Older women with overweight and obesity had higher testosterone levels vs. women with normal weight.
Researchers also found that, compared with women aged 70 to 74 years, SHBG levels were on average 5.6% higher among women aged 75 to 79 years, 13.6% higher in women aged 80 to 84 years and 22.7% higher in women aged at least 85 years (P < .001 for all). Obesity, however, was associated with a 27% lower SHBG level (P < .001).
“The increasing proportion of women with unmeasurable [estradiol] in the older groups most likely reflects different effects of age on the enzymatic pathways essential for the biosynthesis of these hormones,” the researchers wrote. “Regardless, a key message from the findings is that studies investigating the association between estrogens and diseases of aging in postmenopausal women must measure [estrone] in order to provide meaningful findings.”
The researchers noted that the high androgen levels observed in some women in the cohort reaffirm the “wide range of normality” within a community-based population and support the representativeness of the study sample.
“The study suggests that higher testosterone may confer a survival advantage, particularly considering that between the ages of 70 to 95 years, older women have higher testosterone levels in this age group,” Davis said. – by Regina Schaffer
For more information:
Susan R. Davis, MBBS, can be reached at the Women’s Health Research Program, Monash University School of Public Health and Preventive Medicine, 553 St. Kilda Road, Melbourne 3004, Australia; email: susan.davis@monach.edu.
Disclosures: The authors report no relevant financial disclosures.
Sharon Parish, MD
This is new information, and it provides a starting point for better understanding the association between sex steroids and some of what we study related to androgens in women.
There is a widely held belief that declining testosterone levels are responsible for changes in sexual function in women as they age. Additionally, there is a lot of discussion about how useful it is to measure testosterone or other androgens to assess or appraise sexual function. What follows is whether measuring androgens confers a predictive value as to whether women will benefit from supplementation, and whether androgen levels are perhaps biomarkers for longevity.
This study provides more complexity, but also more information, about whether this question of whether testosterone decline with age has a relationship to sexual function. What is striking here is that we now have good measurements providing age-specific data, which we did not have before, suggesting that testosterone levels went up and were higher among women as they age.
The authors are not commenting about the relationship between these measurements and global sexual function, so I would like to see how this fits into the schema of what we understand about sexual function. The other interesting finding here is that testosterone and estrone levels go up as DHEA declines. We need to understand how that influences some of the clinical issues related to androgen levels.
Sharon Parish, MD - Professor of Clinical Medicine in Clinical Psychiatry - Weill Cornell Medical College - Disclosures: Parish reports she has served as a consultant for AMAG Pharmaceuticals, Dare Bioscience, JDS Therapeutics, Procter & Gamble, Sprout, Strategic Science & Technologies and Therapeutics MD, served on an advisory board for AMAG Pharmaceuticals and has received writing support from AMAG, Sprout and Therapeutics MD.
Source: Davis SR, et al. J Clin Endocrinol Metab. 2019;doi:10.1210/jc.2019-00743.
Disponível em: https://www.healio.com/news/endocrinology/20190821/higher-testosterone-level-may-confer-survival-advantage-in-older-women
[[B] https://raypeatforum.com/community/threads/test-for-estrogenic-activity-and-prostate-cancer.7886/ e https://raypeatforum.com/community/threads/while-estradiol-falls-estrone-rises-with-age-and-is-much-more-relevant-for-estrogen-driven-diseases.30568/
[C] PASQUALINI J R GELLY C NGUYEN B L, 1989. Importance of estrogen sulfates in breast cancer. Journal of Steroid Biochemistry Volume 34, Issues 1–6, 1989, Pages 155-163 https://doi.org/10.1016/0022-4731(89)90077-0Get rights and content “Estrogen sulfates are quantitatively the most important form of circulating estrogens during the menstrual cycle and in the post-menopausal period. Huge quantities of estrone sulfate and estradiol sulfate are found in the breast tissues of patients with mammary carcinoma. It has been demonstrated that different estrogen-3-sulfates (estrone-3-sulfate, estradiol-3-sulfate, estriol-3-sulfate) can provoke important biological responses in different mammary cancer cell lines: there is a significant increase in progesterone receptor. On the other hand, no significant effect was observed with estrogen-17-sulfates. The reason for the biological response of estrogen-3-sulfates is that these sulfates are hydrolyzed, and no sulfatase activity for C17-sulfates is present in these cell lines.
[3H]Estrone sulfate is converted in a very high percentage to estradiol (E2) in different hormone-dependent mammary cancer cell lines (MCF-7, R-27, T-47D), but very little or no conversion was found in the hormone-independent mammary cancer cell lines (MDA-MB-231, MDA-MB-436). Different anti-estrogens (tamoxifen and derivatives) and another potent anti-estrogen: ICI 164,384, decrease the concentration of estradiol very significantly after incubation of estrone sulfate with the different hormone-dependent mammary cancer cell lines. No significant effect was observed for the uptake and conversion of estrone sulfate in the hormone-independent mammary cancer cell lines. Progesterone provokes an important decrease in the uptake and in estradiol levels after incubation of [3H]estrone sulfate with the MCF-7 cells.
It is concluded that in breast cancer: (1) Estrogen sulfates can play an important role in the biological response of estrogens; (2) Anti-estrogens and progesterone significantly decrease the uptake and estradiol levels in hormone-dependent mammary cancer cell lines; (3) The control of the sulfatase and 17β-hydroxysteroid dehydrogenase activities, which are key steps in the formation of estradiol in the breast, can open new possibilities in the treatment of hormonedependent mammary câncer”. Disponível em: https://www.sciencedirect.com/science/article/abs/pii/0022473189900770
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