US researchers found that hormone replacement therapies (HRT) commonly prescribed to treat symptoms of menopause were linked to slightly faster loss of brain tissue in areas important for thinking and memory in women aged 65 and over. However, it is possible that any links with increased risk of dementia were only relevant to those women who were already experiencing symptoms when they started on HRT said the researchers.
The research comes from two studies reporting findings from a substudy of the National Institutes of Health’s (NIH’s) landmark Women’s Health Initiative (WHI) hormone therapy clinical trials called the Women’s Health Initiative Memory Study and that appear as companion papers in the 13 January issue of Neurology.
Previous research showed that HRT comprising conjugated equine estrogens (CEEs, used extensively in HRT), with or without progestin, made it more likely that older women on these treatments would have more difficulty with thinking and memory, and experience cognitive impairment or dementia.
These drugs also increase the risk of stroke, so it was assumed that the impact on thinking and memory came from brain lesions due to loss of blood flow that occurs with strokes, including the “silent” strokes. However, these studies showed that the number of brain lesions were not significantly higher among women on HRT, but the volume of brain tissue in those parts of the brain that are important for thinking and memory were shrinking faster than normal in women on HRT.
In the first study, lead investigator Dr Laura Coker of Wake Forest University Baptist Medical Center, and colleagues found that HRT was not linked to an increase in silent strokes or small vascular lesions in the brain.
In the second study, lead author Dr Susan Resnick, of the NIH’s National Institute on Aging, and colleagues found that women who took HRT had slightly smaller volumes of brain tissue in two areas that are important for thinking and memory: the frontal lobe and the hippocampus. A shrinking hippocampus is also thought to be a risk factor for dementia.
For the first study, Coker said they asked themselves what was likely to be the mechanism that linked HRT and the negative impact on thinking and memory.
“We thought it was silent cerebrovascular disease,” said Coker in a press statement.
“So we designed a study to obtain MRI scans of women’s brains to look for increased volumes of brain lesions among those participants who had taken hormone therapy, compared to those who had not,” added Coker, who said they were surprised when they did not get the result they expected: there was no link between HRT and brain lesion increase.
She and her team examined over 1,400 women aged from 71 to 89 who had been taking part in the WHI hormone therapy studies for an average of four to six years.
For the second study, Resnick and colleagues studied data on the same WHI women that Coker and her team examined. They suggest one explanation for the increased risk of dementia in older women who had been on HRT in the WHI study was the possibility that the HRT had a “negative effect on brain structures important in maintaining normal memory functioning”.
But Resnick added that the negative effect was much higher in women who may already have been experiencing problems with thinking and memory before they started on HRT, suggesting that the hormone therapy may have accelerated a disease that had already started rather than kicked it off.
Doctors are advised to prescribe HRT only if needed to treat symptoms of the menopause, and patients should take the lowest dose for the shortest time needed to gain relief. Symptoms of menopause usually affect women between the ages of 48 and 55, and it is not recommended to treat women over 65 with HRT because the benefits aren’t worth the risks.
The findings of Resnick and her colleagues suggest that older women who are already experiencing problems with thinking and memory when they start HRT are the ones who are most at risk in terms of potential effect on the brain and cognitive skills. But, their findings also suggest that women who aren’t experiencing such difficulties before they start HRT are also less likely to experience adverse effects on their brains.
In the next stage of their investigations, the researchers will be looking at whether the effect on brain volume continues during follow up, and they will also be looking at younger women who took HRT nearer the menopause to see if they show the same or different pattern of effects on thinking, memory and brain structure, said Coker.
The WHI is a 15-year program of studies looking at causes of death, disability and poor quality of life in postmenopausal women. The program is funded by grants from the National Heart, Lung, and Blood Institute of the NIH. The sub-study on memory is also supported by Wyeth Pharmaceuticals, Inc.
As well as Wake Forest, 15 other universities are involved. The whole WHI program comprises a total participant base of over 161,000 women aged from 50 to 79 at 40 clinical centers throughout the US, and is thought to be the largest clinical trial ever to take place in the US.
“Postmenopausal hormone therapy and subclinical cerebrovascular disease: The WHIMS-MRI Study.”
L. H. Coker, P. E. Hogan, N. R. Bryan, L. H. Kuller, K. L. Margolis, K. Bettermann, R. B. Wallace, Z. Lao, R. Freeman, M. L. Stefanick, S. A. Shumaker For the Women’s Health Initiative Memory Study.
Neurology January 13 2009, Volume 72, Issue 2, pp 125-134.
“Postmenopausal hormone therapy and regional brain volumes: The WHIMS-MRI Study.”
S. M. Resnick, M. A. Espeland, S. A. Jaramillo, C. Hirsch, M. L. Stefanick, A. M. Murray, J. Ockene, C. Davatzikos For the Women’s Health Initiative Memory Study.
Neurology January 13 2009, Volume 72, Issue 2, pp 135-142.
Sources: Wake Forest University Baptist Medical Center, journal abstract.
Written by: Catharine Paddock, PhD