Hormone Replacement Therapy May Shrink Women's Brains

The use of commonly prescribed forms of postmenopausal hormone therapy may slightly accelerate the loss of brain tissue in women aged 65 and older beyond what normally occurs with age, new research suggests.

The findings stem from the Women's Health Initiative Memory Study (WHIMS). Initial results of the WHIMS indicated that treatment with estrogen, with or without progesterone, increased the risk of dementia and overall cognitive decline in women 65 years of age or older.

Imaging studies conducted approximately 8 years after the study began on roughly 1400 of the original participants showed that women who had taken hormone therapy had slightly smaller brain volumes in two critical areas of the brain: the frontal lobe and the hippocampus. Both areas are involved in thinking and memory skills, and loss of volume in the hippocampus is a risk factor for dementia.

The average frontal lobe volume was smaller by an average of 2.37 cubic centimeters in women treated with hormone therapy compared with women treated with placebo. The average volume of the hippocampus was 0.10 cubic centimeters smaller. However, the difference in total brain volume was not statistical significant.

"Our findings suggest one possible explanation for the increased risk for dementia in older women who had previously taken post-menopausal hormone therapy in the Women's Health Initiative Memory Study," said study chief Dr. Susan M. Resnick, at the National Institute on Aging in Baltimore.

"Our findings suggest that hormone therapy in older post-menopausal women has a negative effect on brain structures important in maintaining normal memory functioning. However, this negative effect was most pronounced in women who already may have had some memory problems before using hormone therapy, suggesting that the therapy may have accelerated a neurodegenerative disease process that had already begun," Resnick said.

In a separate analysis, the WHIMS group, led by Dr. Laura H. Coker at Wake Forest University Health Sciences Center in Winston-Salem, North Carolina, found that brain shrinkage is apparently unrelated to an increase in brain lesions.

"The detrimental cognitive effects of hormone therapy reported in WHIMS may be primarily related not to vascular disease but to neurodegeneration," Dr. Coker and associates suggest. These effects may be mediated by triggering the accumulation of amyloid or other toxic compounds or by reduced cerebral blood flow.