Endogenous oestrogens predict 4‐year decline in verbal fluency in postmenopausal women: the Rancho Bernardo Study

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Abstract
Summary: Objective  Despite overwhelming biological plausibility, evidence for a protective effect of oestrogen on cognitive function in postmenopausal women is inconsistent. This study examines the association between endogenous oestrogen levels and subsequent 4‐year decline in cognitive function test performance in community‐dwelling older women.Design  Longitudinal cohort study.Participants  Three hundred and forty‐three postmenopausal women (median age 70 years).Measurements  Between 1984 and 1987, serum for measurement of sex hormones was obtained along with relevant covariates. Cognitive function was assessed in 1988–1991 and again in 1992–1996 using the Category Fluency test, the Mini‐Mental Status Exam (MMSE) and Trail Making Test B (Trails B).Results  Women in the highest tertile of oestrone and bioavailable oestradiol had respectively 1·75 (95% CI 1·02, 3·07) and 1·79 (95% CI 1·04, 3·10) higher odds of 4 year decline in Category Fluency, a test of frontal lobe function, compared to those in the lowest tertile, independent of age and education. The 20% of women with highest tertile levels of both oestrone and bioavailable oestradiol had a twofold higher odds of verbal fluency loss (OR = 2·17; 95% CI 1·21, 3·89). Adjustment for testosterone levels or for obesity‐related factors associated with high endogenous oestrogens (higher body mass index, waist girth, and triglycerides and lower high‐density lipoprotein cholesterol) did not alter results. Neither oestrogen was associated with change in MMSE or Trails B scores.Conclusions  Higher endogenous oestrogen levels were associated with a greater decline in verbal fluency in postmenopausal women. This association was not explained by elevated androgens or by obesity or obesity‐related factors.