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Early postmenopausal hormone therapy may prevent cognitive impairment later in life

Bagger, Yu Z. MD; Tankó, László B. MD, PhD; Alexandersen, Peter MD; Qin, Gerong MD; Christiansen, Claus MD, PhDfor the PERF Study Group


Objective: Estrogen deficiency has been implicated as a risk factor for cognitive impairment in elderly women, yet the role of hormone therapy (HT) to prevent this event remains controversial. The aim of this study was to investigate the impact of administration of HT for 2 to 3 years in the early postmenopausal years on the risk of cognitive impairment 5 to 15 years later.

Design: We followed a group of 343 women who had received HT in randomized, placebo-controlled trials and were reexamined 5, 11, or 15 years after completion of therapy. Of these women, 261 received either HT or placebo for 2 to 3 years during the trials with no further hormone treatment until follow-up, and the remaining 82 women reported either prolonged or current use of HT at reexamination. Outcome of the study was cognitive function assessed by the short Blessed test that includes tests of orientation, concentration, and memory function on a scale of 0 to 28 (score ≥6 indicates cognitive impairment).

Results: The mean age of participants at follow-up was 65 ± 3 years. There was no difference in the mean cognitive scores between ever HT users and never users. For women who received 2 to 3 years of HT, the risk of cognitive impairment (cognitive score ≥6) was decreased by 64% (odds ratio [OR]: 0.36, 95% CI: 0.15-0.90; P = 0.03). A similar OR was found in long-term/current HT users. Adjustment for age, alcohol intake, current smoking, and education did not alter the results.

Conclusion: The results of the present study suggest that previous short-term HT administered in the early phase of the menopause may provide a long-term protection against cognitive impairment.

The present study is the first to provide evidence for the long-term protective effect of 2 to 3 years of HT administered in the early postmenopausal years against cognitive impairment. The reduction in risk achieved by such therapy was 64% compared with those receiving placebo.

From the Center for Clinical and Basic Research A/S, Ballerup, Denmark.

Received October 19, 2003; revised and accepted March 11, 2004.

Address correspondence to: Yu Z. Bagger, MD, Center for Clinical and Basic Research A/S, Ballerup Byvej 222, DK-2750 Ballerup, Denmark. E-mail:

©2005The North American Menopause Society