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Estrogen therapy may contribute to delaying Alzheimer’s disease

NASHVILLE, Tenn. — Estrogen therapy in women ages 50 to 63 has been shown to affect the metabolic processes associated with later development of Alzheimer’s disease and may offer an opportunity to prevent or delay the disease, according to a presenter at the American College of Obstetricians and Gynecologists Annual Clinical and Scientific Meeting.

After age and presence of the apolipoprotein E4 genetic allele, female sex is the next greatest risk factor for developing Alzheimer’s disease, a risk that increases further in cases of premature menopause, Marcelle I. Cedars, MD, director of the University of California San Francisco Center for Reproductive Health, told attendees.

“The fact there is no effective treatment and that the prevalence of Alzheimer’s disease will triple by the year 2050 from 5.7 million to 14 million has made primary prevention a primary goal for medical and public health professionals,” she said.

Previous animal studies and basic science research have supported the idea of a benefit of estrogen, as it interrupts the increase of amyloid deposits and suppresses accumulation of the tau protein, both associated with the development of Alzheimer’s disease. However past clinical trials, such as the Women’s Health Initiative Memory Study (WHIMS), have only indicated potential risk, Cedars said. Many of these trials were targeted in women where cognitive function was already diminished, whereas the metabolic processes the lead to Alzheimer’s begin much earlier.

More recently, the concept of a critical window for the use of estrogen and timing of onset of estrogen therapy, she said.

“We are starting to see this concept of timing and when estrogen is introduced in terms of cognitive health,” she said. “While the data are mixed, there have been studies that have suggested that estrogen therapy as short as 2 to 3 years may have long-term benefit decreasing cognitive impairment 5 to 15 years later by up to 60%.”

In addition, the MIRAGE study, indicated there was a benefit shown for women who take estrogen between the ages of 50 and 63, but no benefit after the age of 64, she said.

A prospective randomized control trial of the effect of estrogen therapy delivered in early menopause on Alzheimer’s disease outcomes is not feasible or cost-effective, so clinicians and researchers will have to continue to extrapolate from animal studies, basic science, translational studies and from looking at surrogate markers for Alzheimer’s disease, such as neuroimaging, Cedars said.

“Further investigation must critically look at the timing of estrogen, the type of estrogen and the duration of estrogen exposure that’s required ... to delay or prevent Alzheimer’s,” she said. – by Chris Rosenberg

Reference: Cedars M. “Menopause: Cognition and menopause.” Presented at: American College of Obstetricians and Gynecologists Annual Clinical and Scientific Meeting; May 3-6, 2019; Nashville.

Disclosures: Healio Primary Care Today was unable to determine Cedars’ relevant financial disclosures prior to publication.