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Yet More Bad News About Hormone Therapy, This Time for Cognitive Function

In a previous report from the randomized Women's Health Initiative Memory Study (WHIMS), combined hormone therapy (conjugated equine estrogen [CEE] plus progestin) was associated with an increased risk for dementia and cognitive decline, compared with placebo (Journal Watch Jun 13 2003). Now, the WHIMS researchers present analogous findings for 2947 women with prior hysterectomy (age range, 65-79) who received CEE alone or placebo.

Mean follow-up was about 5 years. CEE-alone recipients showed a nonsignificant increase in risk for dementia compared with controls; the increase became statistically significant when data from the CEE-alone and CEE-plus-progestin arms of the study were combined. Findings were similar, although not statistically significant, for mild cognitive impairment (MCI). CEE-alone recipients did have a significant increase in risk for the combined endpoint of probable dementia and MCI. Finally, a small but significant decline was found in global cognitive function in CEE-alone recipients.

Comment: Yet another purported benefit of postmenopausal hormone therapy -- positive effects on cognitive function -- appears to have been refuted by the WHI results. An editorialist notes that other hormone preparations, different dosages, different routes of administration, longer follow-up protocols, and subgroup analyses still could show some benefit of hormone therapy on cognitive function, but such studies are unlikely to be done at this point. In any case, the use of usual dosages of CEE, with or without progestin, to improve cognitive function cannot be recommended.

— Thomas L. Schwenk, MD

Published in Journal Watch General Medicine July 16, 2004

Citation(s):

Shumaker SA et al. Conjugated equine estrogens and incidence of probable dementia and mild cognitive impairment in postmenopausal women: Women's Health Initiative Memory Study. JAMA 2004 Jun 23/30; 291:2947-58.

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Espeland MA et al. Conjugated equine estrogens and global cognitive function in postmenopausal women: Women's Health Initiative Memory Study. JAMA 2004 Jun 23/30; 291:2959-68.

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Schneider LS. Estrogen and dementia: Insights from the Women's Health Initiative Memory Study. JAMA 2004 Jun 23/30; 291:3005-7.

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• Medline abstract (Free)