The Women's Health Initiative Memory Study: findings and implications for treatment

Abstract

Background: The population of the developed world is ageing; consequently there is an increasing prevalence of age-related neuropsychiatric disorders, such as dementia of any cause and Alzheimer's disease (AD), for which few treatments are available. Observational studies suggested that hormone therapy (HT) might protect postmenopausal women against cognitive decline and AD. However, the results of randomised controlled trials in women age 65 years and older were negative. There has been extensive media coverage of these trials and many doctors are asked whether HT improves or worsens brain function in younger women who are prescribed HT for the treatment of menopausal symptoms.

Recent developments: The Women's Health Initiative Memory Study (WHIMS) was a multicentre, randomised, double-blind, placebo-controlled clinical trial in which a subgroup of women who participated in the Women's Health Initiative study were assessed for the effects of HT on dementia and mild cognitive impairment. There were two study arms, one involving 4532 postmenopausal women who received continuous combined oestrogen (conjugated equine oestrogens [CEE] plus medroxyprogesterone acetate) or placebo, and the other involving 2947 hysterectomised women randomised to continuous unopposed CEE or placebo. All participants were age 65 years or older. CEE with or without medroxyprogesterone acetate, given to women age 65 years and older, does not protect against dementia or cognitive decline, but substantially increases the risk of dementia of any cause and cognitive decline. WHERE NEXT?: WHIMS answered critically important questions about whether HT can protect against dementia in elderly women who start HT some years after menopause. However, several clinically important questions are unanswered, including questions about the generalisability of WHIMS to groups of women for whom HT is an indication-perimenopausal women and those soon after menopause who have menopausal symptoms-and other methods of treatment delivery and treatment regimens.