Dementia rates increase for older women on HRT

No change yet in FDA-approved uses

Older women taking combination hormone therapy had dementia twice as often as women not taking the therapy, according to a recently published study.

The results of the Women’s Health Initiative Memory study (WHIMS) were published in the May 28 issue of the Journal of the American Medical Association. WHIMS, a substudy of the Women’s Health Initiative program (WHI), was funded by Wyeth Pharmaceuticals. Wyeth produces Prempro, a form of estrogen plus progestin hormone therapy.

Women ages 65 or older at greater risk

WHIMS studied about 4,500 women who were between 65 and 79 years of age. Once they were initially judged not to have dementia, the women were randomly assigned to take one pill per day of Prempro (conjugated equine estrogen, 0.625 mg, plus medroxyprogesterone acetate, 2.5 mg) or a placebo. Researchers evaluated the women’s cognitive status annually, and any of the women who showed signs of decline were evaluated in greater depth.

The findings showed that over a five-year period:

• The risk for dementia among women taking estrogen and progestin was twice that of women taking placebo pills. This represents an increase per year from 22 women per 10,000 at risk of dementia in the placebo group to 45 women per 10,000 in the combination therapy group. Sixty-one cases of dementia were diagnosed among the women participating in the study; 66% of those cases occurred among women on combination therapy, while 34% occurred in women taking placebo.

• Most of the dementia found among women participating in the study was classified as probable Alzheimer’s disease, with vascular dementia ranking second. There were 20 cases of Alzheimer’s disease among the 40 dementia cases in women in the combination therapy group (50% of the cases); in women on placebo, 12 of the 21 cases of dementia (57%) were deemed Alzheimer’s disease.

• There was no significant difference between the groups in the risk of being diagnosed with mild cognitive impairment.

The Alzheimer’s Association in Chicago expressed disappointment with the results. "This clinical trial was prompted by a wide range of observational and laboratory data that suggested HRT [hormone replacement therapy] reduced women’s risk of developing dementia, including Alzheimer’s," said Marilyn Albert, PhD, in a statement. Albert is professor of neurology at Johns Hopkins University School of Medicine in Baltimore and is the chair of the Alzheimer’s Association Medical and Scientific Advisory Council. "No one anticipated this outcome."

Researchers, however, advise practitioners to keep the study results in perspective. The risk of dementia is significant when viewed over a large population of women, but the risk to individual older women is relatively small. In addition, Wyeth points out that the applicability of these findings to the typical current user — a younger, symptomatic woman taking hormone therapy to relieve menopausal symptoms — is unclear. This study evaluated women who were, on average, age 71 at enrollment, a population at higher baseline risk than the average woman entering menopause, who is age 51, the company says. There also is a question regarding whether the timing of therapy initiation relative to the onset of menopause may be an important factor.

No labeling changes yet

Although the latest results from the WHI study indicate an increased incidence of dementia and memory impairment in older women, the U.S. Food and Drug Administration (FDA) announced in late May that there was no need to modify the approved uses of these drug therapies. The FDA says it is reviewing the new information and will determine whether labeling should be updated so women and prescribers are more fully informed about use of these therapies.

The FDA continues to emphasize that combined estrogen and progestin is effective for treating moderate-to-severe symptoms of hot flashes and night sweats and for treatment of moderate-to-severe symptoms of vulvar and vaginal atrophy. When intended for prevention of osteoporosis, approved non-estrogen treatments should be considered. Estrogen, and estrogen with progestin, also have never been approved for prevention of cognitive disorders, such as Alzheimer’s disease or memory loss.

If physicians advise that estrogen- and progestin-containing products are appropriate for their patients, the products should be used at the lowest dose for the shortest duration to reach treatment goals.