Brain Protection in a Patch

Estrogen is a hormone that regulates a woman’s menstrual cycle, protects her bone health, helps to keep her cholesterol in check — and is crucial to fertility.

It may now also protect brain function and decrease the risk of Alzheimer’s disease when given early in menopause.

“This finding has the potential to change the concepts for preventive interventions that drive the Alzheimer’s disease field today,” said one researcher.

Researchers discovered recently that newly post-menopausal women who received estrogen via a skin patch had reduced beta-amyloid deposits — the sticky plaques found in the brains of people with Alzheimer’s disease. Ultimately, these deposits harm neurons, leading to cognitive problems. The Mayo Clinic study appears in this month’s Journal of Alzheimer’s Disease.

In the study, women with APOE e4 — one form of the most common gene associated with late-onset Alzheimer’s disease — had lower levels of amyloid deposits.

“This study showed, for the first time, that the brain amyloid deposition — a hallmark of Alzheimer’s disease — is reduced in newly post-menopausal women who received 17beta-Estradiol patch form of hormone therapy,” said lead author Kejal Kantarci, M.D., a Mayo Clinic radiologist. “Women with APOE e4, who have a greater genetic risk for Alzheimer’s disease, particularly benefited from this therapy.”

Menopause is defined as occurring 12 months after a woman’s last menstrual period and marks the end of the menstrual cycles. In the U.S., the average age of menopause is 51. A rapid decline in estrogen with menopause may be associated with an increased risk of Alzheimer’s disease risk in women.

The Women’s Health Initiative study by the National Institutes of Health reported that menopausal hormone therapy begun by women 65 or older increased the risk of dementia. In contrast, the multi-center Kronos Early Estrogen Prevention Study tested the hypothesis that healthy and younger women would respond to menopausal hormone therapy more favorably.

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The Mayo Clinic study used data from the Kronos study to determine the effects of menopausal hormone therapy shortly after menopause, during the critical window of rapid estrogen depletion — which happens five to 36 months past menopause.

Researchers investigated the brain amyloid deposition in 68 women ages 42 to 59 who participated in the Kronos trial during this critical window. The researchers used positron emission tomography, also known as a PET scan, to look for the brain amyloid deposits three years after the trial ended.

Of the 68 women, 21 received estrogen via a skin patch, 17 received estrogen orally, and 30 received a placebo. Amyloid deposition was lower in women who received the patch, compared to the placebo, and the effect was most apparent in women with the APOE e4 genotype. The oral treatment was not associated with lower amyloid deposition.

The authors are seeking funding to perform amyloid PET imaging at eight more Kronos Early Estrogen Prevention study 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,” said Dr. Kantarci. “It also may have a significant impact on women making the decision to use hormone therapy in the early post-menopausal years.”

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