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

P>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 center dot 75 (95% CI 1 center dot 02, 3 center dot 07) and 1 center dot 79 (95% CI 1 center dot 04, 3 center dot 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 center dot 17; 95% CI 1 center dot 21, 3 center dot 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.