Estrogen Replacement Therapy for Treatment of Mild to Moderate Alzheimer Disease: A Randomized Controlled Trial

It seems that women are at greater risk of developing Alzheimer’s disease than are men, and, because they also live longer, about twice as many women have the disorder. An abrupt fall in estrogen production in the postmenopausal years might increase vulnerability to Alzheimer’s disease. There is considerable evidence that estrogen may improve cognitive function and mood in patients with Alzheimer’s disease. This randomized, placebo-controlled, double-blind trial enrolled 120 women with mild to moderate Alzheimer’s disease who received conjugated equine estrogens (Premarin, Wyeth-Ayerst Labs, Philadelphia, PA) in a daily dose of 0.625 or 1.25 mg or a placebo. After 12 months, there was a 3-month single-blind placebo washout phase for all women. All participants had undergone hysterectomy. The primary outcome measure was the score on the Alzheimer’s Disease Cooperative Study (ADCS) version of the Clinical Global Impression of Change (CGIC) scale (semistructured interview). The Mini-Mental State Examination (MMSE), Clinical Dementia Rating (CDR) Scale, Hamilton Depression Scale, and the revised Multiple Affect Adjective Checklist also were used, along with other measures of verbal learning, attention, and memory.There were no differences between the Premarin recipients, collectively, and women given placebo in the risk of worsening CGIC or MMSE scores. CDR scores favored the placebo recipients. The treatment and placebo groups did not differ significantly in measures of mood, memory, attention, or activities of daily living. One language measure, category fluency, favored the women given placebo. Comparable results were noted when the two dose groups were analyzed separately, except that MMSE scores favored low-dose estrogen. There was no evidence of improved global functioning at any time. A year of Premarin therapy did not slow the progression of Alzheimer’s disease in these women, improve global or functional outcomes, or enhance cognitive function. It remains possible that estrogen might have a role as an adjuvant treatment or delay the onset of disease.JAMA 2000;283:1007–1015