By LEE BOWMAN, Scripps Howard News Service

Published: May 27, 2003, 01:01:00 PM PDT

(SH) - Older women taking the most common combination of hormone replacement therapy had twice the rate of dementia, including Alzheimer's disease, than women who were not taking the drug, according to a study published Wednesday. The study also found that the combination therapy did not protect against the development of mild cognitive impairment or memory decline less severe than dementia.

The results, published in The Journal of the American Medical Association, are part of a series of reports coming out of the Women's Health Initiative that looked at the effects of the estrogen plus progestin therapy on a variety of health conditions that seem to get worse after menopause.

Doctors halted all experiments with combination therapy last summer after researchers concluded that increased risk of breast cancer, heart disease, stroke and blood clots among the participating women outweighed benefits of reduced risk for hip fracture and colorectal cancer.

"Because of the potential harm and lack of benefit found, we recommend that older post-menopausal women not take the combination hormone therapy to prevent dementia," said Sally Shumaker, a professor of public health sciences at Wake Forest University Baptist Medical Center in Winston-Salem, N.C., and principal investigator for the study, carried out at 39 sites around the country.

Experts stress that the combination therapy only has been evaluated in women over age 65 and that the relative risks and benefits of short-term use of the drug by younger women for relief of some symptoms of menopause remain uncertain.

The researchers said that while the increased risk of dementia calculated over a larger population of women is significant, the risk to any particular woman is still relatively small. Of 10,000 older women who might take the treatment, there would be an additional 23 cases of dementia per year.

"This is not good news, but a woman in her 50s suffering from hot flashes should realize that the women in this group that showed a slight worsening of cognitive function were over age 65," said Dr. Steven Goldstein, a gynecologist and professor of medicine at New York University and leading expert on menopause and estrogen therapy.

Wyeth Pharmaceuticals, which makes Prempro, estimates that about 1.2 million women are still taking the tablets, down from about 3.4 million before the government-sponsored studies were stopped last year.

The treatment also is available in patches and creams, and experts aren't sure if those delivery methods carry the same risks as the tablets.

The recent study included 4,532 postmenopausal women 65 and older who were followed for an average of four years before the study was halted. The women continue to be monitored. Almost half the women received a daily tablet of the combination estrogen plus progestin, marketed as Prempro, and the rest of the women received a pill with no active ingredients.

Cognitive status was evaluated annually and women who showed signs of memory decline were examined in greater depth. A total of 61 cases of dementia were diagnosed among all the women in the study. Sixty-six percent of those cases occurred among the women taking the combination therapy.

Scientists who had long thought that hormone supplements might forestall many effects of aging still aren't sure why the therapy instead seems to boost the risk of dementia, but Shumaker and her colleagues speculate that increased strokes and blood clots might be at least part of the explanation.

The researchers are continuing with a second study to assess the brain effects of estrogen-only therapy among a group of 3,000 women who have had a hysterectomy. Estrogen alone for women with their uterus intact is not recommended, since it has been shown to increase the risk of uterine cancer.