Up to three times as many women as men develop Alzheimer’s disease. Estrogen is capable of protecting central nervous system function through multiple mechanisms. It protects against neuronal cytotoxicity induced by oxidation, reduces the serum concentration of amyloid P component (the glycoprotein found in Alzheimer’s neurofibrillary tangles), and increases synapses and neuronal growth, especially dendritic spine density. Estrogen protects against the cerebrovascular toxicity exerted by amyloid peptides, and promotes synaptic formation and neuronal growth and survival. Case-control and cohort findings indicate that Alzheimer’s disease and related dementia occur less frequently (perhaps as much as 60% less) in estrogen users, and the effect is greater with increasing dose and duration of use.
Short-term administration of unopposed estrogen to patients with Alzheimer’s disease has been reported to improve cognitive performance, but mostly to have no effect. The administration of combined estrogen and progestin also has failed to demonstrate a beneficial impact (secondary prevention) in Alzheimer’s disease. Use of estrogen has been reported to enhance the beneficial response to tacrine in women with Alzheimer’s disease, but overall, the evidence is consistent with a failure of estrogen to influence preexisting disease.
The cancellation of the estrogen-progestin clinical trial arm of the Women’s Health Initiative (WHI) has made decision-making regarding postmenopausal hormone therapy (HT)—who should take it, in which form, and for how long—more difficult than ever. Complex clinical decisions, however, should never be based exclusively upon a single, solitary fact or one scientific study, no matter how large or rigorously conducted. Clinicians should continue to draw on the large body of knowledge that has been published over the last 20 years to make informed decisions, on a patient-by-patient basis, that translate the accumulated knowledge into effective and appropriate clinical practice.
To aid in this important but admittedly challenging process, this issue of the newsletter of the Council on Hormone Education presents a critical appraisal by Dr. Michelle P.Warren of the WHI data. Included are a review of the findings regarding cardiovascular health, fracture results, and breast and colorectal cancers. Dr. Warren puts the WHI results in context, evaluating them against those of earlier controlled trials and observational studies. We hope you find this information both interesting and useful.