Older postmenopausal women who take combination hormone replacement therapy are twice as likely to develop dementia as peers who do not take hormones, according to an article in the May 28th issue of the Journal of the American Medical Association. The researchers also found that combination therapy had no benefit in decreasing risk for mild cognitive impairment.

"Because of possible harm in some areas and lack of a demonstrated benefit in others, we have concluded that combination hormone therapy should not be prescribed at this time for older, postmenopausal women to maintain or improve cognitive function," said Judith A. Salerno, M.D., M.S., of the National Institutes of Health.

In the current work, a substudy of the Women’s Health Initiative, a major, multicenter trial, the risk for dementia was assessed in women age 65 years or older who used Prempro ?, a particular product containing estrogen and progestin, for a 5-year period. The memory substudy was funded by the manufacturer of the combination product, while the larger study has been funded by the National Institutes of Health.

In evaluating the findings, it is important to note that all component substudies of the Initiative that involved use of combination hormone replacement therapy discontinued use of the medication in July 2002 when researchers realized that therapy was associated with increased risk for breast cancer, heart disease, stroke, and thromboembolic events and that these risks outweighed benefits for decreased bone density/hip fractures and colorectal cancer.

Sally A. Shumaker, Ph.D., lead author of the current study, and her colleagues also emphasized in their public announcement that the data should be viewed in perspective. Although the increased risk of dementia is significant when calculated over a large population of women, the risk to any individual older woman is actually
relatively small.

The risk for development of dementia among women who took the combination product was twice that of women who took a placebo, a risk of 45 women per 10,000 in the hormone therapy group versus 22 women per 10,000 in the placebo group. In actuality, 61 women of a total of 4,500 were diagnosed with dementia during the study, with 66 percent of the cases occurring in women taking combination therapy.

Most of the diagnoses were classified as probable Alzheimer’s disease, with vascular dementia the second most common diagnosis. Of the 40 affected women in the combination therapy group, 50 percent (20 cases) were diagnosed with Alzheimer’s disease. The percentage of probable Alzheimer’s disease as a diagnosis was similar for the placebo group (12 of 21 cases, 57 percent).

There was no significant difference in the risk of mild cognitive impairment alone for the two groups of women.

Enrollment criteria included baseline screening tests for dementia, and then the women were randomized to the combination product or a look-alike placebo. Cognitive status was evaluated annually, and any woman who showed suggestions of decline was fully evaluated.

The researchers looked at several other factors that might influence cognitive status, including socioeconomic status, educational attainment, history of prior estrogen or progestin use, and use of cholesterol-lowering medications or aspirin or another nonsteroidal anti-inflammatory drug. These factors were not significantly different between the therapy group and the placebo group and did not account for the differences in rates of cognitive decline, according to the researchers.

For more information, physicians can check the Menopausal Hormone
Therapy Information page (http://www.nih.gov/PHTindex.htm) on the website of the National Institutes of Health.