Menopausal Hormone Therapy and Cognition

Pauline M. Maki, PhD

There is considerable debate about the effects of menopausal hormone therapy (MHT) on cognition and risk for Alzheimer’s disease (AD). Small randomized trials show benefits of estrogen therapy (ET) on memory performance following oophorectomy. In a 2017 JAMA publication, ET reduced risk of death from AD by 26% in the Women’s Health Initiative (WHI). Similarly, meta-analyses of observational studies showing a 29% reduced risk of AD among women with a history of MHT use, commonly of estrogen alone. Four larger randomized, placebo-controlled trials show neutral effects of MHT on cognitive test performance in early postmenopausal women. A series of randomized trials showed neutral cognitive effects of ET on cognition, even in older women. Evidence harm with MHT comes from data from the Women’s Health Initiative Memory Study (WHIMS) showing a doubling of AD incidence in women aged 65 years and older with combination MHT. Overall, MHT is not recommended for primary prevention of AD or treatment of cognitive dysfunction, but instead is thought to have neutral effects when administered in the early postmenopause. The effects of MHT on cognition in women with bothersome vasomotor symptoms are unknown but evidence links VMS with memory dysfunction, suggesting potential benefit for those women.


Dr. Pauline M. Maki is Professor of Psychiatry, Psychology and Obstetrics & Gynecology and serves as Senior Director of Research at the Center for Research on Women and Gender at the University of Illinois at Chicago. Dr. Maki received her Ph.D. from the University of Minnesota and postdoctoral training at the Johns Hopkins University School of Medicine and the National Institute on Aging. For the past 20 years, she has led a program of NIH-funded research on women, cognition, mood and dementia, with a particular focus on the menopause. She uses multiple methods including clinical trials of hormonal and non-hormonal treatments for vasomotor symptoms, cohort studies of the natural history of cognition and brain function across the menopausal transition, and neuroimaging studies.

Dr. Maki is Past President of the North American Menopause Society (NAMS), Current Trustee of the International Menopause Society, Chair of the Society for Women’s Health Research Interdisciplinary Network on Alzheimer’s Disease, and Immediate Past Head of the Neurocognitive Working Group of the Women’s Interagency HIV Study. She won the 2018 Woman in Science Award from the American Medical Women’s Association and the Thomas B. Clarkson Outstanding Clinical and Basic Science Research Award from the NAMS. She has won a number of NIH awards for her research and service, serves as a research and career mentor to many students and junior faculty, serves on executive committees for several women’s health advisory boards, and is a frequent international and national speaker.