# Admin Supplement - Prevention of Alzheimer's disease in women: risks and benefits of hormone therapy

> **NIH NIH RF1** · MAYO CLINIC ROCHESTER · 2020 · $415,612

## Abstract

ABSTRACT
The use of exogenous hormones to treat the neurological symptoms associated with menopause as well as
diseases of aging such as Alzheimer's disease (AD) is controversial. This controversy arose from several
clinical trials including the Women's Health Initiative (WHI) memory study (WHIMS), the WHI study of cognitive
aging (WHISCA), the WHI study of memory in younger women (WHIMSY), Early vs Late Intervention
Treatment with Estrogen (ELITE) where menopausal hormone therapy (HT) either did not prevent dementia, or
increased dementia and adverse cognitive effects. Collectively, these results of these studies suggest that HT
may be effective if used within a critical window around menopause but not in in older women. The type of MT
and route of exposure (i.e. oral conjugated equine estrogen [oCEE] vs. transdermal E2 [tE2]) are also important
and studies such as the Kronos Early Estrogen Prevention Study (KEEPS), a double blind randomized clinical
trial, have investigated effects of these MT on cognitive when given within 3 years of the onset of menopause.
Variation in responses to HT may be related to pharmacokinetics and bioavailability associated with
administering an exogenous estrogen. For example, in the KEEPS cohort, genetic variants of two genes
encoding two different proteins involved in estrogen metabolism and transport i.e. SULTA1 and SLCO1B1
respectively, were associated with severity of menopausal hot flashes. In this supplemental grant, the goal is to
investigate genetic variation in women in the KEEPS continuation study, which aims to investigate the effects
of HT and any correlations to AD, thirteen years after the administration of HT. The genetic analysis will be
expanded to include additional genes involved in estrogen pharmacokinetics, as well as those encoding
proteins involved in estrogen signaling/pharmacodynamic pathways, which may impact response to hormone
therapy in relation to cognition and brain structure and function. The results from this study will lead to a better
understanding of the impact of genetic variation in estrogen pharmacokinetic and pharmacodynamic pathways,
provide insight to the controversy of HT for AD therapy, and lead the way to developing individualized
treatment approaches to AD.

## Key facts

- **NIH application ID:** 10163429
- **Project number:** 3RF1AG057547-01S1
- **Recipient organization:** MAYO CLINIC ROCHESTER
- **Principal Investigator:** CAREY E GLEASON
- **Activity code:** RF1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $415,612
- **Award type:** 3
- **Project period:** 2017-09-15 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10163429

## Citation

> US National Institutes of Health, RePORTER application 10163429, Admin Supplement - Prevention of Alzheimer's disease in women: risks and benefits of hormone therapy (3RF1AG057547-01S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10163429. Licensed CC0.

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