Potential Role for Estrogen Replacement in the Treatment of Alzheimer’s Dementia

In light of evidence that estrogen replacement therapy (ERT) might affect cholinergic function, we examined possible effects of ERT on clinical and cognitive responses to the cholinesterase inhibitor tacrine in women with Alzheimer’s disease (AD). In a previously reported 30-week, randomized, double-blind, placebo-controlled, multicenter clinical trial, 14.5% of 318 women with evaluable data had been receiving ERT prior to randomization. Patients were randomly assigned to receive placebo or one of three ascending dosages of tacrine (maximum dosages of 80 mg/day, 120 mg/day, or 160 mg/day). Women completing the trial receiving ERT and tacrine improved more than women not receiving ERT who were randomized to tacrine or to placebo as assessed by cognitive (p<0.01), clinical (p = 0.02), caregiver (p = 0.006), and mental status (p = 0.07) ratings. Using an intent-to-treat analysis, they improved significantly on cognitive ratings (p = 0.01). These results provide evidence that prior and continuing ERT may enhance response to tacrine in women with AD. Randomized trials are needed.