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Postmenopausal hormone therapy has been linked to brain shrinkage in women aged 65 and older, a pair of studies has found.

Researchers used MRI scans to analyze the brains of more than 1,400 women aged 71 to 89 who had taken part in the Women's Health Initiative, a research trial that compared the health status of those taking hormone therapy versus a placebo.

The new studies were published in today's issue of Neurology.

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A WHI sub-study, which looked at memory and was dubbed WHIMS, showed that hormone therapies that used estrogen alone or combined with progestin increased the risk for dementia and cognitive decline in women 65 and older.

Susan Resnick, a senior investigator at the U.S. National Institute on Aging and lead author of the paper on brain volume, said the findings suggest one possible explanation for the increased risk of dementia in older women who had been assigned hormone therapy as part of the study.

The researchers found that specific areas of the brain involved with memory storage, memory retrieval and thinking - the hippocampus and frontal lobe - had smaller volumes in these women compared with those given a placebo. As well, overall brain volume was slightly lower.

On average, the hippocampus was 1.7 per cent smaller, the frontal lobe was reduced about 1 per cent and total brain volume was down about 0.5 per cent, the researchers found.

However, Dr. Resnick stressed, "these negative effects were most evident in the women who may have already had some memory problem before using hormone therapy. So women who had the lowest global cognitive function scores at the time that they enrolled in the WHI were the ones that had a bigger negative effect."

It may be the women were already vulnerable, she said. "It suggests that what the hormone therapy may be doing is accelerating a neurodegenerative disease process that had actually already begun."

The original WHI studies were halted in 2002 and 2004 after researchers found a higher rate of heart attack, strokes and blood clots among women taking the hormones compared with those getting a dummy pill.

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Because of this higher risk for cardiovascular events, researchers originally hypothesized that it was brain lesions from silent, asymptomatic strokes that were behind the diminished memory and thinking ability among some women.

But Laura Coker, lead author of the companion MRI study, found that wasn't the case.

"It's very common for these signs to show on MRI scans up to 10 years prior to [being]symptomatic," said Dr. Coker, a cognitive scientist at Wake Forest University School of Medicine in Winston-Salem, N.C.

"So we looked at these lesion volumes and we did not find what we expected to find. We saw very little difference in the volumes of brain lesions between women who had taken estrogen-based hormone therapy compared to women who had taken a placebo."

Current recommendations say that in women under 65, hormone therapy should be used only if needed to treat menopausal symptoms, and taken at the lowest dose for the shortest time possible to relieve symptoms, which generally appear in women aged 48 to 55.

Women aged 65 and older should not begin hormone therapy at all because the risks outweigh possible benefits.

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Dr. Resnick said the new findings suggest that older women who were already having some cognitive problems at the time they began hormone therapy were most at risk for negative effects on the brain, while women who were healthy when they began taking hormones were less likely to have adverse effects.

The researchers would like to perform brain scans on younger women to see how the drugs may have affected brain structure and cognitive function.

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