U.K. — Researchers followed the participants for an average of 13.3 years and identified 3,948 cases of dementia during that period. Of those cases, 1,993 were Alzheimer's disease and 1,955 were unspecified or non-Alzheimer's dementia. Women diagnosed with dementia had a mean baseline age of 65, while those without dementia had a mean baseline age of 60. In both groups, most women experienced natural menopause at a mean age of 50.

Anne-Marie Minihane, PhD, of the University of East Anglia, led the study. She said that in addition to living longer, the reason behind the higher female prevalence is thought to be related to the effects of menopause on brain metabolism and the impact of the main genetic risk factor APOE4 being greater in women. She added that while hormone replacement therapy has long been prescribed primarily to relieve menopausal symptoms such as hot flushes and night sweats, this work suggests it may also play a role in long-term cognitive health for some women.

Aimee Spector, Professor, commented on the implications of the timing data. She said this supports the 'window of opportunity' hypothesis, suggesting that HRT use during the menopause transition phase, where symptoms are typically more problematic, is important. Susan Kohlhaas, Executive Director of Research and Partnerships, noted the need for further investigation.

Kohlhaas said this study alone isn’t enough to tell us whether HRT should be used to reduce dementia risk, but it provides further evidence that the timing of HRT and a woman’s hormonal history may matter. She added that research is now needed to establish whether hormone replacement therapy itself is responsible for these differences in dementia risk and to understand which forms of hormone replacement therapy may have an effect.

Why It Matters

Women account for nearly two-thirds of Alzheimer's disease cases, making the relationship between menopause and cognitive health an area of study. Hormone replacement therapy use among postmenopausal women in the U.S. declined from 1999 to 2020. This decline followed a report from the Women's Health Initiative Memory Study in 2003, which stated that estrogen-plus-progestin formulations increased probable dementia risk in women ages 65 or older.

What's New

Later reporting provided additional context on the study's funding and broader implications. The study was funded by the Biotechnology and Biological Sciences Research Council. Amanda Collis, Executive Director for Research Strategy and Programmes, stated that the study provides valuable new insights into how menopause and the timing of hormone replacement therapy may influence dementia risk in women. David Llewellyn, Professor, described the results as a significant step forward, noting that researchers have been able to identify which women are most likely to benefit and when. Susan Kohlhaas emphasized that research is needed to establish whether hormone replacement therapy itself is responsible for these differences in dementia risk and to understand which forms may have an effect. Historical reference material included a publication in the International Journal of Middle East Studies titled Judith E. Tucker, Women in Nineteenth-Century Egypt, Cambridge Middle East Library (Cambridge: Cambridge University Press, 1985). Pp. 251. - Earl L. Sullivan, Women in Egyptian Pub.

How Sources Differ

Sources presented different levels of detail regarding hormone replacement therapy. The Alzheimer's & Dementia journal article reported that hormone replacement therapy use was associated with a lower risk of Alzheimer's disease with a hazard ratio of 0.84 (95% CI 0.77-0.92, P<0.001). The journal also reported that women carrying the APOE4 gene who used hormone replacement therapy had a hazard ratio of 0.87 (95% CI 0.80-0.95) for dementia risk.

Additionally, the journal noted that hormone replacement therapy use was not associated with a lower risk of non-Alzheimer's dementia (HR 0.95, 95% CI 0.87-1.04, P=0.28). The article detailed that starting hormone replacement therapy between ages 46 and 50 was associated with a hazard ratio of 0.87 (95% CI 0.80-0.95, P=0.002) for dementia risk, while starting between ages 51 and 56 was associated with a hazard ratio of 0.77 (95% CI 0.70-0.86, P<0.001). Women who underwent surgical menopause and used hormone replacement therapy had a hazard ratio of 0.74 (95% CI 0.65-0.84) for dementia risk compared to non-users. The Alzheimer's & Dementia journal article also reported that hormone replacement therapy use was associated with a lower risk of all-cause dementia with a hazard ratio of 0.90 (95% CI 0.84-0.96).