The brain-volume findings, published in the journal Neurology, are the latest from the Women's Health Initiative, a landmark government study of postmenopausal women. Over the last six years, it has firmly established that, contrary to decades of conventional wisdom, the risks of hormone therapy outweigh the benefits.

Today's finding also came with a surprise. Researchers had theorized that supplemental estrogen, with or without the synthetic hormone progestin, caused memory and thinking problems by triggering tiny, symptomless strokes. But the new research, which involved magnetic resonance imaging (MRI) of the brains of 1,400 Women's Health Initiative participants, linked cognitive problems to brain shrinkage - not strokes.

This was a cross-sectional study of women who had participated in two previous randomised control trials. These earlier studies were part of the Women’s Health Initiative Memory Study (WHIMS)

The WHIMS study assessed the effects of certain HRT treatments on cognition and dementia risk in women aged over 65 years. The HRT treatments used were either “conjugated equine oestrogens” (CEE) or a combined treatment of medroxyprogesterone with CEE.

In the first trial women in the trial were randomly assigned to take CEE medication or a placebo pill. In the second trial women took a combined treatment or a placebo pill.

The trial had found that those taking either form of HRT were at increased risk of dementia and negative effects on their cognition and that there was no reduction in risk of mild cognitive impairment. This was particularly evident in women who had low cognitive function prior to the start of the trial. These studies was stopped early because of these adverse events.

Hormone replacement therapy, a regimen of progestin and estrogen given to relieve symptoms of menopause, initially fell from favor in 2002 when the Women's Health Initiative Memory Study was stopped because of concerns that the treatment was putting the women involved at greater risk for stroke and heart problems.

"Older women who took these [hormones] ... they had greater brain atrophy in these brain regions that are critical for the maintenance of memories," said Susan Resnick, a senior investigator at the National Institute on Aging, Laboratory of Personality and Cognition, and the study's primary author.

In this new study, women older than 65 were shown to have an decrease in brain volume if they took the hormone therapy. In the past, such reduction in brain size had been associated with a decline in memory, and Resnick expects those results to replicate when they analyze cognition test scores.

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