Can Estrogen Help Protect Women Against Dementia?

What to know about new research linking estrogen levels to dementia risk.

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Researchers at the Alzheimer’s Association International Conference (AAIC) in Chicago revealed some interesting research for women approaching menopause.

New research has found a link between dementia and estrogen levels — the more estrogen a woman receives from pregnancy, for example, the less the risk of diseases like Alzheimer’s.

Additionally, there’s new evidence that hormone replacement therapy (HRT) may affect cognition in some subgroups of women.

“I think it’s very interesting,” said Dr. Verna R. Porter, director of programs for dementia, Alzheimer’s disease, and neurocognitive disorders at Pacific Neuroscience Institute at Providence Saint John’s Health Center in California.

What did the study find?

The recent findings reported at the AAIC in July included a large-scale epidemiological investigation in the United States by researchers, including Paola Gilsanz, ScD, staff scientist at Kaiser Permanente Northern California Division of Research in Oakland, California, and Rachel Whitmer, PhD, a professor at UC Davis.

The team looked at women’s first menstrual period, the number of children they had, and when they started menopause to see what link there may be to dementia risk.

The researchers found that women in the study with three or more children had a 12 percent lower risk of dementia compared to those with only one child.

Also, women who reported having their first menstrual period at 16 or older had a 31 percent greater risk of developing dementia than those who reported having their first period at 13.

And, there was a 28 percent greater dementia risk for women experiencing menopause at 45 or younger compared to women who started after age 45.

How HRT could also affect dementia risk

Another study reported at the conference, from researchers at the Wisconsin Alzheimer’s Disease Research Center and other institutions, found no negative cognitive effect in women who had started hormone therapy between ages 50 and 54.

However, those who started hormone therapy between ages 65 and 79 did show reductions in global cognition, working memory, and executive functioning.

Women on hormone therapy with type 2 diabetes also demonstrated a higher risk of cognitive impairment compared to women without diabetes on hormone therapy and women with diabetes who were given a placebo.

“It may be that it’s critical when you give it,” said Porter regarding determining success or failure of hormone replacement therapy (HRT), and adding that risk factors like diabetes may also provide some context in whether to prescribe HRT.

These findings join previous research which found that estrogen and progestin therapy actually increased the risk for dementia in postmenopausal women 65 years and older.

Porter said the question remains whether estrogen is directly affecting cognitive function or if it’s something else.

She said that women experience an increase in certain immune cells during pregnancy, promoting regulatory T cells.

Alzheimer’s patients have fewer regulatory T cells, which promotes inflammation. Could the T cell increase during pregnancy be involved with the lower dementia risk?

“I think one of the main possibilities that is being postulated based on all these different studies [is] it’s not that it’s female sex hormones on their own,” said Porter.

Instead, it may be that these hormones have additional effects on other factors that influence cognition, said Porter.

What women should think about with hormone therapy

Porter said based on the new findings, there may be some cognitive benefit of hormone replacement therapy when given at the right time.

This could mean giving HRT during the transition into menopause, as long as women don’t have risk factors for dementia, like bad cardiovascular health.

But any decisions about HRT should be based on gynecological history, including menopausal symptoms like hot flashes — not just potential cognitive benefit.

She said it should be something where many factors are taken into account.

“This new information is one important piece of the puzzle,” said Porter.

Dr. William R. Shankle, The Judy & Richard Voltmer endowed chair in memory and cognitive disorders at Pickup Family Neurosciences Institute at Hoag in California, recommends that women get a second opinion if their doctor says to not take estrogen because it’s bad for you.

However, there are certain circumstances when estrogen replacement therapy (ERT) can’t be prescribed, including for women with estrogen-sensitive breast cancer.

“If you are approaching menopause, are in menopause, or have completed it within the past five years, get a gynecologist who is knowledgeable about ERT so you can decide whether to take it,” said Shankle. “If you have not taken ERT and [are] more than five years past menopause, the current science indicates that ERT is not helpful and may increase risk of dementia due to [Alzheimer’s disease] or other causes.”

Dr. Russell Swerdlow, director of the University of Kansas Alzheimer’s Disease Center, said there are still no firm answers on the question of whether estrogen can help prevent dementia.

“This [research] adds to the list of reported associations between female hormones, such as estrogen, and cognitive performance,” said Swerdlow. “Associations such as these have spurred interest into the question of whether hormone replacement can benefit cognition.”

Swerdlow pointed out currently “the aggregate of results is not promising” but said that continuing research may eventually help clarify the benefits and risks.

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