Alzheimer's Disease Education and Referral Center

Hormone therapy linked to brain shrinkage

May 12, 2009

Two recent imaging studies shed light on how menopausal hormone therapy (MHT) may affect the brains of older women. Previous studies showed that MHT increased the likelihood that older women would have difficulty with thinking skills and memory and develop dementia or cognitive impairment.

In the first study, researchers with the Women’s Health Initiative Memory Study-MRI (WHIMS-MRI), an ancillary study of the Women’s Health Initiative (WHI) hormone therapy clinical trials, took MRI brain scans of approximately 1,400 women 79 to 89 years of age 1 to 4 years after the WHI hormone trials ended. They found that women who had taken MHT had smaller brain volumes in two brain areas than women who had taken a placebo. Brain volume was lower in the frontal lobe and in the hippocampus, areas involved in thinking and memory skills. Loss of volume in the hippocampus is a risk factor for dementia.

“Our findings suggest one possible explanation for the increased risk for dementia in older women who had previously taken MHT in the WHIMS,” said lead author Dr. Susan Resnick of the NIA’s Intramural Research Program. “The findings also suggest that hormone therapy in older postmenopausal 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 MHT, suggesting that the therapy may have accelerated a neurodegenerative disease process that had already begun.”

Dr. Resnick emphasized that the women in this study were randomly assigned to MHT later in life than the usual period of treatment around the time of the menopausal transition. It remains unclear whether earlier MHT given only during the period of most intense menopausal symptoms is associated with poorer cognition.

In the second study, researchers analyzing the MRI scans found that MHT was not linked to an increase in volumes of small vascular lesions in the brain that are often the first sign of cerebrovascular disease. Lead author Dr. Laura Coker of Wake Forest University noted that the negative effects of MHT on cognitive skills may not be related primarily to vascular disease but to neurodegeneration, which is supported by the first study’s findings of brain atrophy. 


Resnick, S.M., et al. Postmenopausal hormone therapy and regional brain volumes: the WHIMS-MRI Study. Neurology. 2009 Jan 13. 72(2):135-42.

Coker, L.H., et al. Postmenopausal hormone therapy and subclinical cerebrovascular disease: the WHIMS-MRI Study. Neurology. 2009 Jan 13. 72(2):125-34.

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