June 22, 2004
Two large new studies offer compelling evidence that hormone replacement therapy during menopause does not protect older women against Alzheimer's disease and other forms of dementia. In fact, hormone therapy may even slightly raise the risk of Alzheimer's in older women. The results solidify earlier findings and reports citing the possible hazards of hormone therapy.
For years, the female sex hormones estrogen and progestin were given to older women to ease hot flashes, vaginal dryness, and other symptoms of menopause. Doctors were hopeful that the hormones, alone or in combination, would strengthen bones, ward off heart disease, and even protect the brain against the ravages of Alzheimer's disease and premature forgetfulness.
In the past several years, however, findings from the Women's Health Initiative, a rigorous long-term study of more than 25,000 older women, and other reports have raised serious questions about the safety of such treatment. Women who took supplemental estrogen and progestin were found to have a slight but significantly increased risk of heart attacks, strokes, and breast cancer. Those who took estrogen alone, an option open to women who have had a hysterectomy, also had an increased risk of strokes.
The latest reports, from the Women's Health Initiative Memory Study, or WHIMS, followed a subset of nearly 3,000 women from the Women's Health Initiative to look for signs of Alzheimer's or other forms of mental or memory decline. They ranged in age from 65 to 79, and were taking either estrogen (at a dose of 0.625 mg a day) or a look-alike pill (placebo). The investigators also analyzed earlier results from women who were taking both estrogen plus progestin.
They found that women who were taking estrogen alone did not have a lower incidence of Alzheimer's disease. Nor were they less likely to develop mild cognitive impairment, or MCI, a milder form of memory loss that in some cases presages the onset of Alzheimer's. Similarly, the combination of estrogen and progestin did not reduce the likelihood of developing dementia or MCI among these older women. The authors conclude that, "Use of hormone therapy to prevent dementia or cognitive decline in women 65 years of age or older is not recommended."
Additional research from the WHIMS study found that women aged 65 and older who took hormone replacement therapy had, on average, a greater decline in overall mental function than those who took a dummy-pill (placebo). "We found that women aged 65 years or older assigned to [estrogen] therapy had a slightly but significantly lower average cognitive function compared with women assigned to placebo, as measured during 5 to 7 years of follow-up," the authors write. "These differences appeared to emerge 1 to 2 years after initiation of therapy and persisted throughout the trial." Those women who had the lowest scores on memory and mental function tests at the start of the study tended to fare the worst.
These studies provide further evidence that older women should not choose hormone replacement to protect against Alzheimer's or mental decline. It is possible that different combinations, forms, or doses of these and related hormones may offer women some additional benefits with fewer risks. It is also possible that taking hormone replacement for short periods, just a year or two, during menopause may offer some kind of protection for the brain or other organs. However, more study is needed to answer these and other questions. Women considering hormone replacement therapy should discuss their options with their doctors.
The results appeared in the June 23/30 issue of the Journal of the American Medical Association. For more information on hormone replacement therapy and Alzheimer's disease, visit www.ALZinfo.org.
Sally A. Shumaker; Claudine Legault; Lewis Kuller; et al: for the Women's Health Initiative Memory Study: "Conjugated Equine Estrogens and Incidence of Probable Dementia and Mild Cognitive Impairment in Postmenopausal Women: Women's Health Initiative Memory Study." JAMA. 2004;291:2947-2958.
Mark A. Espeland; Stephen R. Rapp; Sally A. Shumaker; et al: for the Women's Health Initiative Memory Study: "Conjugated Equine Estrogens and Global Cognitive Function in Postmenopausal Women: Women's Health Initiative Memory Study." JAMA. 2004;291:2959-2968.
Lon S. Schneider: Estrogen and Dementia: "Insights From the Women's Health Initiative Memory Study" (editorial). JAMA. 2004;291:3005-3007.