Understanding the Role of Estrogen in Alzheimer’s Disease Prevention

Is there a “window of opportunity” for hormone replacement therapy?

Incidence rates of Alzheimer’s disease are expected to more than double by 2050 as baby boomers age – a substantial increase that is expected to create a devastating global burden. Today, no treatments can prevent or “cure” Alzheimer’s. But because Alzheimer’s is primarily a disease of the elderly, interventions that prevent or delay disease onset would have a significant impact on reducing the burden of this debilitating disorder.

Estrogen hormone therapy in some circumstances may help protect the brains of postmenopausal women from decline, although findings have been inconsistent and controversial. But further studies have suggested that the time in a woman’s life at which the therapy is applied may be critical. Based on the results of a number of studies, several researchers have postulated that hormone therapy during a critical midlife period or “window of opportunity” in a woman’s life could provide protection.

For years, hormone replacement therapy has been used to ease some of the side effects of menopause, such as hot flashes and mood swings. But a large clinical trial from the Women’s Health Initiative (WHI) in 2002 linked hormone replacement to a greater range of health risks than previously realized, including increased risk of stroke and at least in some settings, increased risk of heart disease and breast cancer. These findings caused a high percentage of women to discontinue use of hormone therapy and drastically reduced the number of doctors prescribing it. But more recent analysis of the WHI data has suggested that a timing link may exist for some outcomes. For example, there are possible cardiac benefits from hormone therapy, but only in younger postmenopausal women.

The Stanford Center on Longevity teamed with the Stanford Center for Neuroscience in Women’s Health to look further into this complex relationship and move the understanding of this important issue forward. The workshop, supported jointly by the National Institute on Aging and the Center on Longevity, convened a group of the top experts in the field for three days in January 2010. For two days, these experts presented and reviewed the newest science available. Using the Center on Longevity’s Consensus Conference model on the third day, the experts focused on reaching agreement on key issues and defining next steps.They agreed to form a multi-university team with a goal of indentifying the profile of women most at risk for Alzheimer’s disease and determining the window of opportunity when treatment is most likely to have protective effects. This team will examine the basic biology, the genetic factors, and the best ways to have the greatest public health impact on protecting midlife women from Alzheimer’s as they age.


Natalie Rasgon (Chair)
Stanford University

Roberta Diaz Brinton (Co-Chair)
University of Southern California

Victor Henderson (Co-Chair)
Stanford University

Ken Smith (Conference Organizer)
Stanford Center on Longevity

John C.S. Breitner
University of Washington

Margaret Dyer-Chamberlain
Stanford Center on Longevity

Mark A. Espeland
Wake Forest University School of Medicine

Cheryl Frye
The University at Albany-SUNY

Robert Gibbs
University of Pittsburgh

Francine Grodstein
Harvard Medical School

Howard N. Hodis
University of Southern California

Eef Hogervorst
Loughborough University

Jay R. Kaplan
Wake Forest University School of Medicine

Wendy Mack
University of Southern California

Pauline M. Maki
University of Illinois at Chicago

Marilyn M. Miller
National Institute on Aging

Teresa Milner
Weill Cornell Medical College

John H. Morrison
Mount Sinai School of Medicine

Chris Peacock
Stanford Center on Longevity

Walter A. Rocca
Mayo Clinic College of Medicine

Peter J. Schmidt
National Institute on Mental Health

James W. Simpkins
University of North Texas

Kristine Yaffe
University of California, San Francisco