Effect of estrogen therapy and sex on brain structures in aging : importance of lifelong endogenous and exogenous estrogen exposure
Bibliographic record
Abstract
Recently, new findings allow us to suggest that lifelong exposure to endogenous estrogens could be a reliable predictor of the effect of exogenous estrogens on cognition and the brain. Thus explaining why women do not arrive at menopause with an equivalent susceptibility to the effects of estrogen therapy (ET) In the current thesis, studies have been designed to investigate the effect of estrogens on the brain from a new perspective by introducing new measures. Firstly, we developed a questionnaire about indices of lifelong estrogen exposure and assessed the reliability of these self-reported indices over a four year interval. Secondly, we recruited postmenopausal women and men to investigate the effects of estrogens on the brain using magnetic resonance imaging. Volumetric analyses of the hippocampus and amygdala and global automated analysis using voxel-based morphometry (VBM) were performed to assess whether current ET use as well as estrogen exposure throughout life can predict cerebral structural changes. The results demonstrate that most lifelong estrogen exposure indices were reliable with age at menopause and age at HT initiation leading to the weaker correlations. An age effect on the recall of these indices was also observed. The neuroimaging results revealed that women using ET had larger HC volumes compared to past HT users, never users and men. Moreover, we found a negative relationship between ET duration and HC volume among ET users. We confirmed these results with the VBM analysis. These results support the notion that there is a treatment duration-dependent neuroprotective role of estrogen on HC volume in aging that point toward a window of opportunity. Analysing the whole brain using VBM also demonstrated that there are sex differences and that the estrogen effects are not specific to the HC since we found that ET users compared to never users have greater grey matter concentration in the nucleus accumbens and that this effect was modulated by age at menarche and age at menopause. Overall, these results strongly suggest that lifelong endogenous and exogenous estrogen exposures have modulatory neuroprotective effect on the aging brain.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".