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Mayo release touts estrogen patch for reducing Alzheimer’s. But the study looked only at a risk marker.

Alzheimer disease, neuron network with amyloid plaquesROCHESTER, Minn. — Can estrogen preserve brain function and decrease the risk of Alzheimer’s disease when given early in menopause? Newly postmenopausal 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, a Mayo Clinic study published this month in the Journal of Alzheimer’s Disease found. Ultimately, these deposits harm neurons, leading to cognitive problems.

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 Alzheimers disease ─ is reduced in newly  postmenopausal women who received 17beta-Estradiol patch form of hormone therapy,” says lead author Kejal Kantarci, M.D., a Mayo Clinic radiologist. “Women with APOE e4, who have a greater genetic risk for Alzheimers disease, particularly benefited from this therapy.”

MEDIA CONTACT: Susan Barber Lindquist, Mayo Clinic Public Affairs, 507-284-5005,

Menopause is defined as occurring 12 months after a woman’s last menstrual period and marks the end of 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 (NIH) reported that menopausal hormone therapy started in women 65 or older increased the risk of dementia. In contrast, the multicenter Kronos Early Estrogen Prevention Study tested the hypothesis that healthy and younger women would respond to menopausal hormone therapy more favorably.

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 — 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,” Dr. Kantarci says. “It also may have a significant impact on women making the decision to use hormone therapy in the early postmenopausal years.”

Study co-authors are Val Lowe, M.D.; Timothy Lesnick, M.S.; Nirubol Tosakulwong; Kent Bailey, Ph.D.; Julie Fields, Ph.D.; Lynne Shuster, M.D.; Samantha Zuk; Matthew Senjem M.S.Michelle Mielke, Ph.D.Clifford Jack Jr., M.D.; Walter Rocca, M.D.; and Virginia Miller, Ph.D., all of Mayo Clinic; and Carey Gleason, Ph.D., of University of Wisconsin School of Medicine and Public Health.

This study is funded by the Aurora Foundation to the Kronos Longevity Research Institute and NIH. (NS66147, AG029624, AG44170)


About Mayo Clinic
Mayo Clinic is a nonprofit organization committed to clinical practice, education and research, providing expert, whole-person care to everyone who needs healing. For more information, visit and

Estrogen Patch in Newly Postmenopausal Women May Reduce Alzheimer’s Risk

Our Review Summary

skin patchA small pilot study has found that giving recently postmenopausal women estrogen via a patch is associated with reduced depositions of amyloid in the brain (a hallmark of Alzheimer’s disease) relative to women who received estrogen orally or who took a placebo.  Additionally, the study found that the association was strongest among women with a greater genetic risk of Alzheimer’s disease.

The study was carefully done, and the news release offers some useful details about the study’s methods. However, the study included just 68 women, too few to make the patterns found reliable. To its credit, the release quotes the lead author about the need for larger replications. But that begs the question of why the Mayo Clinic seeks to publicize this work at all, particularly with a news release headline that emphasizes disease reduction potential, when the study only looked at amyloid levels, a risk marker. There is very active debate as to whether lowering amyloid will have any impact on actual symptoms or rates of Alzheimer’s disease. A better headline might have been: “Pilot Study Suggests Estrogen Patch in Newly Postmenopausal Women Reduces Amyloid, Marker of Alzheimer’s Risk.” Journalists certainly deserve to know about this study, but they need to keep it in their back pockets until more rigorous clinical studies have been done.


Why This Matters

Whether estrogen replacement therapy is of value to postmenopausal women is contested territory, and researchers, including those in the Kronos Early Estrogen Prevention Study from which this research stems, are trying to explore the contingencies, if any, that distinguish women who could benefit from estrogen supplementation from those who may not.

This study adds to a body of work looking at the “timing hypothesis,” that is, the notion that estrogen has different effects in the heart and brain when given to younger postmenopausal woman compared to women in their 60s or 70s.  Studies of effects on the heart using intermediate disease markers (carotid artery thickness, analogous to heart disease in the way that amyloid deposition is to Alzheimer disease) in lieu of clinical outcomes (heart attacks, cognitive impairment) have been appearing in journals over the past two years. Considered in this context, the research is of interest but needs to be shared with a strong dose of qualifiers.


Does the news release adequately discuss the costs of the intervention?

Not Satisfactory

Costs for hormone therapy are readily available but they are not broached in this release.

Does the news release adequately quantify the benefits of the treatment/test/product/procedure?

Not Satisfactory

Although the news release summarizes the pattern of results—that recently postmenopausal women who received estrogen via a skin patch were found to have “lower” amyloid depositions in their brains relative to those who took estrogen by mouth or who were in the placebo group—that pattern is not explained in any numerical or statistical way.  Is it a strong association?  A weak one?  We have no idea from the release.

According to the published report, the benefits were statistically significant but the sample size was too small to be meaningful. Just 21 of the enrolled women received the patch, 30 received a placebo and 17 received estrogen orally.

Does the news release adequately explain/quantify the harms of the intervention?

Not Satisfactory

Early in the text, the writer notes that one large, older study—the Women’s Health Initiative at NIH—has found an association between use of estrogen and an increased risk of dementia among women 65 or older. The study highlighted here, in contrast, focuses on women five to 36 months past menopause, individuals predominantly in their 50s. The potential long-term effects of estrogen use by these younger women is not mentioned in the release.

Estrogen carries a well-known small increase in risk for breast cancer and blood clots, which could have been briefly acknowledged. In addition, the National Library of Medicine states that estradiol, the form of estrogen used in transdermal patches, “increases the risk that you will develop endometrial cancer (cancer of the lining of the uterus [womb]). The longer you use estradiol, the greater the risk that you will develop endometrial cancer.” Other minor side effects include head ache, breast pain and nausea, among others.

Does the news release seem to grasp the quality of the evidence?

Not Satisfactory

The release offers some specifics about the study design, but it doesn’t highlight the randomized, blinded nature of the study. That said, it describes the study framework:

“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 release includes a comment from the lead study author regarding the need to confirm the findings by replicating the study with larger samples. But even that comment neglects the larger question of whether reducing amyloid has any effect at all on Alzheimer’s symptoms or risk. The overall implication that there’s a causal relationship, strongly inferred in the headline, earns this a not satisfactory rating.

Does the news release commit disease-mongering?


The release doesn’t exaggerate a condition. It states that declines in estrogen associated with menopause “may” be associated with an increased risk of dementia. Unfortunately, that doesn’t give readers a feel for the robustness of the relationship, or for the evidence supporting it.

Does the news release identify funding sources & disclose conflicts of interest?


Funders are identified, and the single scientist in the release is clearly identified as the study’s lead author.

Does the news release compare the new approach with existing alternatives?


The release offers no other approaches available to postmenopausal women for reducing Alzheimer’s disease risk and that’s appropriate in this case. It would be an over-reach to try and name the many other Alzheimer’s disease prevention options being studied.

In addition, the findings address an intermediate endpoint, i.e. amyloid deposition as a disease marker, not the disease itself.

Does the news release establish the availability of the treatment/test/product/procedure?

Not Applicable

It’s common knowledge that numerous estrogen supplements —  including those delivered via patch — are readily available.

Does the news release establish the true novelty of the approach?


The lead author makes a priority claim in the release, which seems to be justified.

Does the news release include unjustifiable, sensational language, including in the quotes of researchers?


Words employed by both the text and the researchers, the latter via quotes, are straightforward.

Total Score: 5 of 9 Satisfactory


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