Estrogen patch reduces hallmark sign of Alzheimer's disease in postmenopausal women

By John Murphy, MDLinx
Published July 15, 2016

Key Takeaways

An estrogen skin patch reduced amyloid-beta deposits—an indication of Alzheimer’s disease—in newly postmenopausal women, reported a July 13, 2016 study in the Journal of Alzheimer’s Disease. If this finding is validated, it could be a game-changing treatment for preventing Alzheimer’s disease, the researchers predicted.

“This study showed, for the first time, that the brain amyloid deposition—a hallmark of Alzheimer’s disease—is reduced in newly postmenopausal women who received the 17β-Estradiol patch form of hormone therapy,” said lead author Kejal Kantarci, MD, MSc, Professor of Radiology at the Mayo Clinic, in Rochester, MN.

“Women with APOE ε4, who have a greater genetic risk for Alzheimer’s disease, particularly benefited from this therapy,” Dr. Kantarci added.

Previous studies of hormone therapy for Alzheimer’s disease have led to controversial results. In the Women’s Health Initiative Memory Study (WHIMS), hormone therapy increased the risk of dementia; however, the subjects in this study were women in late menopause—65 years old and older.

In this new study, researchers investigated whether estrogen could preserve neurological function and decrease the risk of dementia when given to women during a “window of opportunity” in early menopause—5 to 36 months after their final menstrual period. To do so, Mayo Clinic researchers used data from the Kronos Early Estrogen Prevention Study (KEEPS), a multi-center trial that tested whether hormone treatment could slow the progression of atherosclerosis in newly postmenopausal women, ages 42 to 59. (It couldn’t.)

In the KEEPS trial, subjects were randomized to one of three treatments: oral estrogen therapy, estrogen transdermal patch, or placebo pills and a placebo patch. Treatment continued for four years. Three years after treatment stopped and the trial had ended, the Mayo Clinic researchers performed positron emission tomography (PET) to scan for amyloid-beta deposits in a subset of 68 participants who had been enrolled in the KEEPS trial at the Mayo Clinic.

After the researchers adjusted for age, women treated with the transdermal patch had lower measures of amyloid-beta deposits compared with those in the placebo group. However, women treated with oral estrogen therapy did not show fewer amyloid deposits.

The transdermal patch particularly lowered amyloid-beta levels in women with the APOE ε4 genotype. "Women who are APOE ε4 carriers are at a higher risk for Alzheimer’s disease-related pathology and may benefit most from preventive interventions at an early age,” the authors wrote.

Given these results, the Mayo Clinic investigators are now seeking funding to perform PET imaging for beta-amyloid at eight more KEEPS trial sites around the U.S.

“If our results are confirmed in the larger group of women, this finding has the potential to change the concepts for preventive interventions that drive the Alzheimer’s disease field today,” Dr. Kantarci said. “It also may have a significant impact on women making the decision to use hormone therapy in the early postmenopausal years.”

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