Abstract Details

Title Impacts of Menopausal Hormone Therapy on Alzheimer's Disease Biomarkers: A Systematic Review

Topic Aging, Dementia, and Behavioral Neurology

Presentation(s) S15 - Diagnostics, Mechanics, and Mortality of Alzheimer's Disease and Related Dementias (1:48 PM-2:00 PM)

Poster/Presentation
Number 005

Objective To determine how menopausal hormone therapy (MHT) influences validated biomarkers of Alzheimer’s disease (AD) in peri- and postmenopausal women, considering formulation, timing and genotype.

Background Sex-specific vulnerability to AD has been increasingly discussed, with menopause representing a critical neuroendocrine transition. Estrogen and progesterone modulate synaptic plasticity, glucose metabolism, and amyloid and tau homeostasis, yet the clinical impact of their decline and replacement remains controversial. AD biomarkers, such as amyloid, tau, and neuroimaging measures, offer an objective approach to assess MHT’s mechanistic effects beyond cognitive endpoints.

Design/Methods A systematic review was conducted following PRISMA guidelines and registered in PROSPERO (CRD420251149404). Searches of PubMed, Embase, Web of Science, and Cochrane Library through September 2025 identified interventional and observational studies evaluating MHT and AD biomarkers in women after natural menopause. Eligible biomarkers included cerebrospinal fluid (CSF) Aß42, total tau, phosphorylated tau, plasma markers, and amyloid-, tau-, or FDG-PET imaging. Study quality was assessed using RoB-2 and ROBINS-I tools, and evidence certainty was rated with GRADE.

Results From 2480 records, 1429 abstracts were screened, 24 full texts reviewed and 14 studies met inclusion criteria. Early or continuous estradiol-based MHT, especially transdermal 17ß-estradiol, was associated with lower CSF and plasma p-tau181, and preserved glucose metabolism in AD-vulnerable cortical regions. Neuroimaging studies showed decreased amyloid deposition and sustained metabolic benefits years after discontinuation. In contrast, oral conjugated equine estrogens and combined estrogen-progestin regimens were linked to neutral or unfavorable patterns, mainly when initiated over five years after menopause.

Conclusions MHT’s impact on AD biomarkers depends on timing, formulation and composition. Early transdermal estradiol appears to support neuroprotective biomarker profiles, whereas delayed or combined therapies may negate these effects. Harmonized biomarker protocols and genotype-stratified trials are needed to establish optimal therapeutic windows for neuroprotection in women.

Authors/Disclosures
Amanda C. Rodrigues, MS PRESENTER	Miss Rodrigues has nothing to disclose.
Carolina B. Moura, MD (Hospital Universitário Antonio Pedro)	Dr. Moura has nothing to disclose.
Filipe G. Valerio	Mr. Valerio has nothing to disclose.
Gabriel C. Tudella	Mr. Tudella has nothing to disclose.
Anderson Matheus P da Silva, Sr., PhD	Prof. P da Silva has nothing to disclose.
Carlos Eduardo Monforte de Oliveira	Mr. Monforte de Oliveira has nothing to disclose.
Diogo Haddad Santos, MD (Moema)	Dr. Haddad Santos has nothing to disclose.

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