Hormone therapy linked to brain shrinkage: studies

TORONTO—Hormone therapy to treat hot flashes and other symptoms of menopause has been linked to brain shrinkage in women aged 65 and older, a pair of studies has found.
The studies, published in today’s issue of “Neurology,” used MRI scans to analyze the brains of more than 1,400 women aged 71-89.

The women previously had taken part in a Women’s Health Initiative (WHI) clinical trial that compared health effects among those taking hormone therapy versus those on a dummy pill.
A WHI sub-study, which looked at memory and was dubbed WHIMS, showed hormone therapies using estrogen alone or combined with progestin increased the risk for developing dementia and for cognitive decline in women 65-plus.
The two new studies—called WHIMS-MRI—investigated what effect hormone therapy might have had on brain size and whether lesions from any strokes were more extensive in those who had topped up their hormones.
Susan Resnick, a senior investigator at the U.S. National Institute on Aging and lead author of the paper that looked at brain size, said her group’s findings suggest a possible explanation for the increased risk for dementia in older women given hormones as part of the WHI study.
The study found that specific areas of the brain critical for memory storage, memory retrieval, and thinking—the hippocampus and frontal lobe—were smaller in these women compared with those given a placebo.
As well, overall brain size was slightly lower.
On average, the hippocampus was 1.7 percent smaller, the frontal lobe was reduced by about one percent, and total brain volume was down about 0.5 percent, the researchers found.
However, Resnick stressed these effects were most pronounced in those women who already had some memory problems even before starting 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,” Resnick said from Baltimore, adding the women may have been vulnerable.
“It suggests that what the hormone therapy may be doing is accelerating a neurodegenerative disease process that had actually already begun.”
The WHI study involved 15,730 postmenopausal women with an intact uterus, aged 50-79 at enrolment, who randomly were assigned to take estrogen plus progestin or a dummy pill.
The study was halted in 2002, before completion, due to increased rates of breast cancer, heart attacks, strokes, and blood clots among women taking the hormones.
An estrogen-alone arm of the study of women who had undergone hysterectomy was stopped in 2004 over concerns the hormone taken by itself boosted the risk of stroke and blood clots.
Armed with those findings, researchers for the second MRI study thought it must be brain lesions from silent, or asymptomatic, strokes that were causing cognitive problems linked to hormone therapy.
Lead author Laura Coker, a cognitive scientist at Wake Forest University School of Medicine, said it’s common for signs of neuron-killing strokes to show up on MRI scans up to 10 years prior to a person experiencing symptoms.
“So we looked at these lesion volumes and we did not find what we expected to find,” Coker said from Winston-Salem, N.C. “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 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 duration possible.
Women age 65 and older should not begin hormone therapy at all because the risks outweigh possible benefits.
Dr. Christine Derzko, an expert in gynecology and endocrinology at the University of Toronto, said there are many questions about hormone therapy still unanswered, but these two studies help increase knowledge about the drugs’ effects.
“I think it’s really a great relief,” said Derzko, who was not involved in the research. “These papers are lining up right on the right side of our recommendations. . . . If you’re older, this is probably something you should not be taking.
“But this should not, in any way, dissuade a younger women who needs to take hormones for legitimate reasons from taking them,” she stressed.