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Record W4411340484 · doi:10.1210/endrev/bnaf018

The Impact of Estrogen Deficiency on Liver Metabolism: Implications for Hormone Replacement Therapy

2025· article· en· W4411340484 on OpenAlex
Jiawen Dong, Kaitlyn M.J.H. Dennis, Radha Venkatakrishnan, Leanne Hodson, Jeremy Tomlinson

Why this work is in the frame

A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.

fundA Canadian funder is recorded on the work.
no affNo Canadian affiliation: this work is invisible to an affiliation-only frame.
No Canadian affiliation. An affiliation-only frame, the usual design, would never have seen this work. It is one of the works that make the case for inverting the frame.

Bibliographic record

VenueEndocrine Reviews · 2025
Typearticle
Languageen
FieldMedicine
TopicLiver Disease Diagnosis and Treatment
Canadian institutionsnot available
FundersNIHR Oxford Biomedical Research CentreTasmanian Department of HealthMedical Research Council CanadaBritish Heart FoundationNational Institute for Health and Care Research
KeywordsEstrogenHormone replacement therapy (female-to-male)MedicineMenopauseEndocrinologyInsulin resistanceInternal medicineLiver diseaseSteatosisAdipose tissueChronic liver diseaseHormoneNonalcoholic fatty liver diseaseDiseaseFatty liverDiabetes mellitusTestosterone (patch)Cirrhosis

Abstract

fetched live from OpenAlex

Metabolic dysfunction-associated steatotic liver disease (MASLD; previously nonalcoholic fatty liver disease) is the most common chronic liver condition globally. It affects 1 in 3 individuals and is associated with increased liver and cardiovascular mortality. MASLD is a sexually dimorphic condition, and in women the prevalence and severity of MASLD rises significantly following menopause. Preclinical data shows that lack of estrogen promotes multisystem metabolic dysfunction that is characteristic of MASLD. This not only includes hepatic lipid accumulation, insulin resistance, and fibrosis but also extra-hepatic metabolic processes in adipose and skeletal muscle. There are currently no available MASLD treatments tailored to women. The uptake of estrogen-based menopausal hormone replacement therapy (HRT) has seen a dramatic increase in recent years. Despite the changing attitudes toward HRT and the strong evidence base implicating estrogen deficiency in the development of MASLD, the impact of HRT on MASLD in postmenopausal women is poorly studied. In this review, we discuss the burden of MASLD in women, the effect of estrogen deficiency on the processes that drive MASLD development and progression, and the potential sex-specific therapeutic strategies that may prevent or limit MASLD development after menopause.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Not applicable · Consensus signal: none
GenreCandidate signal: Review · Consensus signal: none
Teacher disagreement score0.750
Threshold uncertainty score0.281

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.001
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

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.

Opus teacher head0.052
GPT teacher head0.396
Teacher spread0.345 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it