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Original Investigation
June 12, 2000

Postmenopausal Estrogen and Estrogen-Progestin Use and 2-Year Rate of Cognitive Change in a Cohort of Older Japanese American Women: The Kame Project

Author Affiliations

From the Departments of Epidemiology (Dr Rice), Medicine (Drs Rice, McCormick, and Larson), Psychosocial and Community Health (Dr McCurry), Environmental Health (Dr Gibbons), and Neurology (Dr Bowen), University of Washington, Seattle; and the Department of Epidemiology and Biostatistics, University of South Florida, Tampa (Dr Graves).

Arch Intern Med. 2000;160(11):1641-1649. doi:10.1001/archinte.160.11.1641

Background  The relation between estrogen and cognition among postmenopausal women remains controversial. Also uncertain is whether the proposed association varies between women taking unopposed estrogen and those taking estrogen combined with progestin.

Objective  To determine whether unopposed estrogen and combined estrogen-progestin use were associated with the rate of cognitive change in a cohort of older, Japanese American, postmenopausal women.

Methods  A prospective observational study in a population-based cohort of older Japanese Americans (aged ≥65 years) living in King County, Washington. Cognitive performance was measured in 837 women at baseline (1992-1994) and 2-year follow-up (1994-1997) examinations using the 100-point Cognitive Abilities Screening Instrument (CASI). Least squares means general linear models were used to estimate the 2-year rate of cognitive change according to categories of postmenopausal estrogen use.

Results  Approximately half of this cohort (n=455) had never used estrogen at any time since menopause, 186 were past users, 132 were current unopposed estrogen users, and 64 were current estrogen-progestin users. The majority of current estrogen users were taking conjugated estrogens, and all women receiving combined therapy were taking medroxyprogesterone acetate. After adjusting for age, education, language spoken at the interview, surgical menopause, and baseline CASI score, women who had never used postmenopausal estrogen improved slightly on the CASI scale (mean adjusted change, 0.79; SEM, 0.19). This change was significantly greater for current unopposed estrogen users (mean adjusted change, 1.68; SEM, 0.36; P=.04) and significantly worse for current estrogen-progestin users (mean adjusted change, −0.41; SEM, 0.50; P=.02) compared with never users. The improvement observed in past users (mean adjusted change, 1.12; SEM, 0.29) was intermediate between the changes for never users and current unopposed estrogen users and not significantly greater than that for never users (P=.35).

Conclusions  Our findings support a modest beneficial association between current unopposed estrogen use and the rate of cognitive change. We also observed a modest detrimental association between current estrogen-progestin use and the rate of cognitive change. The clinical significance of these modest differences, however, is uncertain. Data from large, long-term randomized trials are required before applying this information to the clinical setting.