Chapter 23 - The role of sex steroids in Alzheimer's disease: Prevention and treatment

Abstract

There is a strong biologic rationale for the use of estrogen-containing hormone therapy (HT) for the prevention and treatment of Alzheimer's disease (AD). For treatment, clinical trial evidence indicates that beginning HT in the presence of dementia due to AD does not improve symptoms or slow progression. There is no evidence of substantial harm in this setting, but the specific issue of HT discontinuation for women with AD has not been addressed. A more important public health concern is HT use by healthy women without dementia. There is no clinical trial evidence that initiating HT after about age 64 improves memory or other cognitive abilities. In addition, for the older postmenopausal woman, the Women's Health Initiative Memory Study (WHIMS) trials provide strong evidence that HT elevates dementia risk within several years of initiation. However, it is controversial whether WHIMS results should be applied to younger women who were not eligible to enroll in WHIMS protocols. Observational studies, in which HT exposures tended to occur in younger women, indicate that HT use might reduce AD risk. However, potential biases in observational studies remain a strong concern. Fortunately, the incidence of AD is very low during the midlife period, when women and their physicians might consider HT for moderate to severe vasomotor symptoms of the menopause. If HT elevates AD risk in this younger age group, the absolute risk of short-term usage is likely to be low.