Estrogen and Cognition: An Enigma in Postmenopausal Women

JoAnn E. Manson, MD, DrPH


April 05, 2019

This transcript has been edited for clarity.

Hello. This is Dr JoAnn Manson, professor of medicine at Harvard Medical School and Brigham and Women's Hospital in Boston, Massachusetts. I'd like to talk with you about a recent report[1] in the BMJ on postmenopausal hormone therapy and risk for Alzheimer's disease. This was a large case-control study from Finland. My colleague, Dr Pauline Mack, at the University of Illinois in Chicago, and I wrote an accompanying editorial.[2]

This study included more than 80,000 women with a diagnosis of Alzheimer's disease identified from the Finnish national registry. They were compared with a similar number of women without a diagnosis of dementia from the Finnish national population registry, matched for age and region. Information on medication use was obtained from a national drug reimbursement registry in Finland.

What they found is that the use of systemic hormone therapy was associated with a small increase in the risk for Alzheimer's disease—a 10%-20% increase in risk. Women who started hormone therapy before age 60 did not have an increased risk unless they were taking the hormone for at least 10 years. There were no appreciable associations or differences according to the formulation of systemic hormone therapy.

Should these findings change clinical decision-making about hormone therapy use or move the needle in terms of the benefit-risk equation? We think not. There is already a good deal of data from randomized clinical trials that support cognitive safety and lack of adverse effects of hormone therapy when used in early menopause. Even in the Women's Health Initiative trial,[3] among women aged 50-55 at the time of randomization, hormone therapy had a neutral effect on cognition. The KEEPS trial[4] (among women within 3 years of the onset of menopause) and the ELITE trial[5] (within 6 years of menopause onset) showed neutral effects of hormone therapy on cognition.

The observational studies have had mixed and inconsistent results. Some have shown favorable and others unfavorable associations, but observational studies do have potential for confounding and other biases. In this registry study, there was limited information on risk factors. There may have been some differences in cardiovascular risk factors among users and nonusers. Nor was there clear information on the indications for the use of hormone therapy. For example, some women may have been using hormone therapy, especially long-term, because of concerns about memory problems. Because these are prescription medications, women were already in the healthcare system, had frequent interactions with clinicians, and may have been screened more frequently for cognitive decline.

Overall, among women in early menopause who are having bothersome hot flashes, night sweats, disrupted sleep, and impaired quality of life, and no contraindications to hormone therapy, it's likely that the benefits of treatment will outweigh the risks. For women with these symptoms who are not candidates for hormone therapy or who are not interested in treatment, there are nonhormonal options.

Overall, we agree with the national professional guidelines that hormone therapy should not be started or continued for the express purpose of trying to prevent or treat Alzheimer's disease or other forms of dementia. Thank you so much for your attention. This is JoAnn Manson.

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