Clinical Briefs-By Louis Kuritzky, MD

Estrogen Replacement Therapy for the Treatment of Mild to Moderate Alzheimer’s Disease

Since women live longer than men, and Alzheimer’s disease (AD) risk increases with advanced age, the problem occurs with twice the frequency in women. Whether estrogen replacement therapy (ERT) has an effect on AD has been an issue of some debate, and though initial impressions have been positive, the literature has not been definitive. Mulnard and colleagues selected 120 women with mild to moderate AD who had also recently undergone hysterectomy, thus eliminating concern for induction of endometrial hyperplasia by ERT. These women received either 0.625 mg or 1.25 mg estrogen daily for 12 months, or placebo.

Several tools were used for measuring outcome, including the Clinical Global Impression of Change scale (CGIC), the Clinical Dementia Rating Scale (CDR), the Ham Depression Scale, and the Multiple Effect Adjective Checklist. Multiple measurement tools for memory were also included.

There were no measurable persistent effects of ERT on any of the measured parameters, though there was a transient Mini Mental Status Examination improvement. Mulnard et al conclude that ERT therapy does not prevent progression of or improve the status of AD, and comment that the adoption of ERT for AD prior to randomized trials demonstrating its benefit is reason for concern.

Mulnard RA, et al. JAMA 2000;283: 1007-1015.