New results from the Women’s Health Initiative Memory Study of Magnetic Resonance Imaging (WHIMS-MRI)

January 2009

Findings Summary

Between April, 2005 and January, 2006, approximately 1,400 women from 14 sites of the Women’s Health Initiative Memory Study volunteered to receive a brain MRI scan. The Women’s Health Initiative Memory Study (WHIMS) is an ancillary study looking at the role of hormone therapy on cognition and memory in a subset of women enrolled in WHI. This was the most comprehensive examination ever conducted on how postmenopausal hormone therapy affects the structure of women’s brains. The primary results from this study are published in the January 13, 2009 issue of Neurology, the medical journal of the American Academy of Neurology.
The Women’s Health Initiative has shown previously that hormone therapy may increase the chances that women aged 65 years or older may have difficulty with thinking skills and memory and experience dementia or cognitive impairment. Because these drugs are also known to increase women’s risk for strokes, it had been assumed that these drugs adversely affected women’s memory by increasing the rates of “silent strokes” and brain lesions, which are changes in tissue that occur when blood flow to an area of the brain is reduced or blocked. Instead, investigators found that the volumes of brain lesions were not markedly increased among women who had been prescribed hormone therapy, but that the total volumes of brain tissue in regions critical to memory were slightly smaller.
Loss of brain tissue normally occurs with age. It appears that hormone therapy may slightly increase the rate that this occurs in some older women in a way that is separate from the occurrence of strokes. We don’t know, at present, why this occurs. Because of the increased risk of stroke, dementia, and loss of brain tissue that is associated with these drugs, we recommend that health care providers not prescribe postmenopausal hormone therapies to enhance or improve cognitive function in women aged 65 years or older.

Questions and Answers

What is the WHIMS-MRI?
The WHIMS-MRI is a sub-study of the Women’s Health Initiative and the Women’s Health Initiative Memory Study. It is the most comprehensive examination ever conducted on how postmenopausal hormone therapy affects the structure of women’s brains. Between April, 2005 and January, 2006, approximately 1,400 women aged 65 and older underwent magnetic resonance imaging across 14 US academic centers. These women had been enrolled for an average of 4-6 years in the Women’s Health Initiative randomized controlled clinical trials of hormone therapy. In July, 2002 the trial of combination therapy (Premarin® and a progestin: PremPro®) was halted due to an unfavorable risk-to-benefit ratio of its non-cognitive endpoints. In February, 2004 the trial of estrogen-alone therapy (Premarin®) was halted due to an increased risk of stroke, embolic events and the lack of any favorable effect on cardiovascular disease.
The Women’s Health Initiative Memory Study found that women who had been assigned to take these hormone therapies had greater rates of dementia and relatively poorer performance on tests of cognitive function than those women who had been assigned to take placebo. The WHIMS-MRI was designed to see if these adverse affects were associated with greater evidence of ischemia in the brain, such as might be produced from “silent” strokes.
MRI scans were collected 1-3 years after the Women’s Health Initiative trials had ended. Most women had not been using hormone therapies during the period of time when the trials ended and when they received their MRI.
What is cognitive function?
Cognitive function includes brain related abilities like attention, concentration, memory, language, abstract reasoning and calculation.
What is dementia?
When cognitive function declines to the point that it interferes a great deal with day-to-day activities, and other medical conditions have been ruled out, a diagnosis of dementia might be given. Different brain diseases can cause dementia. The most well known is Alzheimer’s disease. Other diseases that block the normal flow of blood in the brain can also cause dementia. What causes these diseases and how they progress is not well understood at this time. However, much research is being done to find treatments that can decrease the effects of these diseases on everyday functioning.
What are brain ischemic lesions?
Ischemic lesions are changes in brain tissue that occur when blood flow to an area of the brain is reduced or blocked. These tend to gradually increase in number as we get older.
What were the main findings from the WHIMS-MRI?
Very little difference was seen in the volume of brain ischemic lesions between women who had taken hormone therapies versus those who had not. Contrary to our original expectations, the hormone therapies did not appear to increase the volume of ischemic lesions in the brain in most women.
Women who had been assigned to take the hormone therapies had slightly smaller brains than those who had been assigned to take placebo. For most women, the amount of brain loss was small and would not be expected to noticeably affect her memory or thinking. Loss of brain tissue is a part of normal aging and does not necessarily signal Alzheimer’s disease.
The WHIMS-MRI also found that the volumes of specific regions of the brain that were critical to memory were also smaller among women who were assigned to take hormone therapy. Women who had lower levels of cognitive function when they enrolled in the Women’s Health Initiative appeared to lose relatively the most brain tissue when assigned to take its hormone therapies.
What are the conclusions from these findings?
The Women’s Health Initiative has shown that hormone therapies involving Premarin® increase the risk of strokes in older women. While relatively rare, these strokes can adversely affect memory and other cognitive functions. The WHIMS-MRI indicates that there may be another way in which these hormone therapies adversely cognition in women aged 65 years or older, which is associated with increased loss of brain tissue that occurs separately from strokes. We don’t know, at present, why this occurs. Because of the increased risk of stroke, dementia, and loss of brain tissue that is associated with these drugs, we recommend that health care providers not prescribe postmenopausal hormone therapies to enhance or improve cognitive function in women aged 65 years or older.