Associations between blood sex hormones, cognitive decline and incident dementia in community-dwelling older Australian women: a prospective cohort study

Objective

Whether blood sex hormone concentrations predict cognitive decline and incident dementia in older women is uncertain. The Sex Hormones in Older Women (SHOW) study is a prospective cohort study of Australian women, aged at least 70 years, without cognitive impairment.

Methods

Sex hormones were measured by liquid chromatography–tandem mass spectrometry, and comprehensive cognitive testing was performed at baseline and 3 years later.

Results

Of the 6,358 participants who had sex hormones measured, 4,444 women (median age at baseline 74 years [Q1–Q3 71.7–77.5]) provided data for cognitive analyses. The findings were limited to a decline in executive function and verbal fluency was positively associated with the highest quartiles of estrone (odds ratio [OR] = 1.21, 95% confidence interval [CI] 1.01–1.45, p = 0.04) and dehydroepiandrosterone (DHEA) (OR= 1.21, 95% CI1.01–1.45, p = 0.04), compared with the lowest quartiles. Estrone and DHEA were not associated with any other cognitive decline. Testosterone was not associated with cognitive decline. In an exploratory analysis, cognitive decline was not different in women who had estradiol below the limit of detection (66% of women) compared with women with measurable estradiol. Over a median 4.1 years of follow-up (22,518 person-years), 121 (2.2%) developed dementia; an incident rate of 5.3 per 1,000 person-years. There were no associations between any hormone and incident dementia.

Conclusions

The finding of a greater likelihood of a decline in executive function and verbal fluency in community-dwelling older women with the highest blood concentrations of DHEAand its metabolite estrone need reaffirmation and their clinical significance should be further investigated. These findings do not support use of estrogen or DHEAtherapy to prevent cognitive decline in older women.

Sultana F, Davis SR, Wolfe RS, McNeil JJ, Islam RM. Associations between blood sex hormones, cognitive decline and incident dementia in community-dwelling older Australian women: a prospective cohort study. Climacteric. 2025 Mar 14:1-10. doi: 10.1080/13697137.2025.2470458. Epub ahead of print.