Estrogen & Dementia, No Significant Link (cont.)

Now, the WHIMS scientists have evaluated the cognition and dementia data from the estrogen-alone part of the trial. Some 2,947 women age 65 to 79 at the beginning of the trial received estrogen alone (a daily dose of 0.625 mg of Premarin™) or a placebo. (The women received estrogen alone because they had all had hysterectomies at some time before beginning the study. A progestin is used with estrogen in menopausal hormone therapy in any woman with a uterus to prevent thickening and, sometimes, cancer of the lining of the uterus, the endometrium. Because the uterus is removed in a hysterectomy, there is no need for progestin when women who have had hysterectomies use menopausal hormone therapy.)

Participants were determined to be dementia free before they were enrolled in WHIMS. At the beginning and then annually for the more than 5-year average duration of the trial, WHIMS participants were evaluated to determine if they might have developed dementia or mild cognitive impairment (MCI). All women received the Modified Mini Mental State Exam (3MSE), and those suspected of having dementia also received an extensive clinical evaluation by a specialist physician.

At the end of the study, the risk of dementia in the estrogen-alone group was 49% higher than the risk in women using the placebo. That is, among 10,000 women using conjugated equine estrogens, 37 could be expected to develop dementia, compared to 25 in 10,000 women using the placebo - 12 extra cases of dementia in every 10,000 women using estrogen alone each year. This increased risk was not statistically significant.

Last year WHIMS scientists reported a 105% increase in the risk of dementia in older women using estrogen plus progestin compared to those using a placebo. That means, on average, each year in 10,000 women over age 65 using estrogen plus progestin there might be 45 cases of dementia compared to 22 cases in 10,000 older women on placebo.

Almost half of the dementia cases in the estrogen-alone study - 46% in older women using estrogen alone and 47% of those in older women using the placebo - were Alzheimer's disease (AD). Similarly, in the estrogen plus progestin study, 50% of the cases in older women using estrogen plus progestin and 57% of those in older women using placebo were classified as AD.

A second article on general cognitive function from Mark A. Espeland, PhD, and other WHIMS investigators appears in the same issue of JAMA. It reports that beginning estrogen-alone hormone therapy after age 65 can have a small negative effect on overall cognitive abilities and that this negative effect may be greater in women with existing cognitive problems. The differences in scores on cognitive testing for the estrogen-alone and placebo groups were statistically significant, but the differences were so small that they are not considered clinically relevant by the investigators.

As with the earlier WHI and WHIMS result reports, these increases in risk must be viewed in perspective. Significant increases in risk are important for public health officials who are concerned with large groups in the population, where a small increase could have health implications for millions of people. For an individual woman, however, the increased risk is still quite small.

Further, these findings relate to women age 65 and older taking this particular estrogen-alone hormone therapy. The cognitive risks and benefits for younger women using Premarin™ or other estrogen formulations are unknown. Any younger woman who is considering menopausal hormone therapy because of her menopausal symptoms should talk to her doctor about how the various Women's Health Initiative study findings relate to her own medical history and treatment.

Source: National Institutes of Health press release June 22, 2004


Last Editorial Review: 6/23/2004