Hormone Replacement Therapy Linked To Brain Shrinkage In Older Women, Study Finds

Hormone replacement therapy may accelerate brain tissue loss in women older than age 64, increasing the risk for dementia and mental decline, according to a study published Tuesday in Neurology, the Philadelphia Inquirer reports. Researchers conducted MRI scans of the brains of 1,400 women ages 71 to 89 who participated in the Women's Health Initiative, a landmark government study in which postmenopausal women were randomly assigned to take HRT or a placebo. Participants in the new study, who were at least 65 when they joined the WHI, had taken either HRT or a placebo for four to six years.

In the new study, researchers had hypothesized that supplemental estrogen, with or without supplemental progestin, caused memory and thinking deficiencies by triggering small, symptomless strokes. However, the brain scans revealed no differences in the amount of brain scarring, a sign of strokes, in women who had taken HRT and those who had not. Instead, the brain scans showed small but significant losses in volume in the frontal lobe and hippocampus -- two critical areas for thinking and memory -- in women who had taken hormones. Women with the greatest shrinkage of the hippocampus had scored poorly on an initial mental-function test at the time of enrollment in the WHI (McCullough, Philadelphia Inquirer, 1/13). Study author Susan Resnick of the National Institute of Aging said that this finding suggests that HRT "may have accelerated a neurodegenerative disease process that had already begun." Resnick said the study suggests that "hormone therapy in older post-menopausal women has a negative effect on brain structures important in maintaining normal memory functioning" (Reuters, 1/13). Resnick said it is unclear how HRT worsened the process, adding that HRT formulas contain so many chemical components that pinpointing a potentially toxic one is difficult.

James Pickar -- assistant vice president for clinical research at Wyeth Pharmaceuticals, which provided the HRT used in the WHI -- said that the new findings do not change the current advice for menopausal women, which is to take HRT only to relieve transitory symptoms, such as hot flashes, in the lowest effective dose for the shortest amount of time needed. Pickar also noted that a 2007 analysis of WHI data found that participants who took HRT before age 65 were 50% less likely than those who did not to develop Alzheimer's disease or dementia. Laura Coker of Wake Forest University -- who was an author of the new research -- plans to conduct mental tests on women who were about age 50 when they enrolled in the WHI to determine how the timing of HRT might affect cognitive function (Philadelphia Inquirer, 1/13).


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