CHICAGO - HORMONE replacement therapy may cause brain shrinkage in women 65 and older, explaining why the drugs increase problems with memory and thinking in older women, US researchers said on Monday.

Researchers had thought hormone replacement therapy (HRT), which is known to increase the risk of strokes, might be causing undetected brain injuries or 'silent strokes' that would explain the higher risk of memory trouble.

Not so, said Dr Laura Coker of Wake Forest University Baptist Medical Center in North Carolina, who worked on one of two related studies in the journal Neurology.

'We hypothesized that we'd see increased silent disease, meaning small strokes, silent strokes and early vascular changes on brain MRI (magnetic resonance imaging) scans. We didn't find that,' Dr Coker said in a telephone interview.

For many years, doctors had thought hormone therapy could protect women from chronic diseases, especially heart disease.

But use of HRT plunged after the 2002 Women's Health Initiative study found that HRT could raise the risk of breast and ovarian cancer, strokes and other serious conditions.

Both brain studies draw from the Women's Health Initiative Memory study, which looked at the effects of HRT on brain function in women over 65. In 2003, that study showed estrogen with or without added progestin increased the risk for dementia. Coker and colleagues wanted to know why.

They checked 1,400 women aged 71 to 89 who had taken hormone therapy for an average of four to six years, using MRI scans to look for what might be causing the memory trouble.

'We saw very little difference in the volume of brain lesions in women who had taken estrogen compared with women who took a placebo,' Dr Coker said in a telephone interview.

'This is not what we expected to find,' she said.

The answer came in a companion study led by Dr Susan Resnick of the National Institute on Aging, which found 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 are involved with memory and thinking.

'Our findings suggest that hormone therapy in older post-menopausal women has a negative effect on brain structures important in maintaining normal memory functioning,' Dr Resnick said in a statement.

The finding was most pronounced in women who already had some signs of mental decline before they began HRT.

Dr Coker said the next step is to do a follow-up MRI study on the women to see if the brain volume changes are lasting.

And the researchers also plan to check women in the original Women's Health Initiative study who were too young at the time to take part in the memory study.

Many experts have said HRT is probably safer for women just beginning menopause, which starts at an average age of 51 but usually begins causing symptoms years earlier.

Most doctors now advise that women use the lowest dose possible of HRT for the shortest possible amount of time to manage the symptoms of menopause. -- REUTERS