Hormone Therapy in Alzheimer Disease Shows Biomarker Signals but Lacks Definitive Evidence: Amanda Rodrigues, MS

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“Our data today is not sufficient to make definitive conclusions and solely for Alzheimer’s disease prevention, hormone therapy is not yet supported.”

Sex-specific vulnerability to Alzheimer Disease (AD) has been increasingly debated, 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 and not fully understood. Biomarkers for the disease such as amyloid, tau, and neuroimaging measures, offer an objective approach to assess menopause hormone therapy’s (MHT) mechanistic effects beyond cognitive endpoints.¹

A study titled “Impacts of Menopausal Hormone Therapy on Alzheimer's Disease Biomarkers: A Systematic Review” aimed to address this controversy by evaluating how MHT influences validated biomarkers of AD in peri- and postmenopausal women, considering formulation, timing and genotype. Led by Amanda Rodrigues, MS, a medical student at Santa Casa de São Paulo School of Medical Sciences in Brazil, the review included interventional and observational studies assessing CSF Aβ42, total tau, phosphorylated tau, plasma biomarkers, and amyloid-, tau-, or FDG-PET imaging. Study quality was assessed using RoB-2 and ROBINS-I, and certainty of evidence was graded using GRADE.¹

Presented at the 2026 American academy of Neurology (AAN) Annual Meeting, held April 18-22 in Chicago, Illinois, findings suggested early or continuous estradiol-based MHT, particularly transdermal 17β-estradiol, was associated with lower CSF and plasma p-tau181, and preserved glucose metabolism in AD-vulnerable cortical regions. Neuroimaging data further indicated reduced amyloid deposition and sustained metabolic effects even after therapy discontinuation. In contrast, oral conjugated equine estrogens and combined estrogen-progestin regimens were associated with neutral or less favorable biomarker profiles, particularly when initiated more than five years after menopause.¹

At the conference, NeurologyLive^® spoke with Rodrigues about her systematic analysis of hormone therapy in AD. She noted that current evidence remains limited and insufficient for firm conclusions, highlighting the need for genotype stratification, standardized biomarker reporting, and better consideration of factors such as BMI, APOE4 status, cortisol, and sleep. Rodrigues also called for expanded research to clarify how hormone-related therapies affect AD biomarkers, particularly in underrepresented populations.

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REFERENCES
1. Rodrigues A, Moura C, Valério F, et al. Impacts of Menopausal Hormone Therapy on Alzheimer's Disease Biomarkers: A Systematic Review. Presented at: 2026 American Academy of Neurology Annual Meeting; April 18-22, 2026; Chicago, Illinois.