Conjugated equine estrogen (CEE) therapies when initiated among older women have been shown to produce small decrements in global cognitive function. We are interested whether these persist after cessation and extend to specific cognitive domains.
Randomized controlled clinical trial
Fourteen clinical centers of the Women's Health Initiative
2,304 women aged 65-80 years and free of probable dementia at enrollment
0.625 mg/day of CEE, with or without medroxyprogesterone acetate (MPA, 10 mg/day), and matching placebos
Annual administrations of a battery of cognitive tests during and following the trial
General linear models were used to compare on-trial and post-trial mean standardized test scores between treatment groups, with adjustment for baseline risk factors for cognitive impairment.
Assignment to CEE-based therapies was associated with small mean relative decrements in global and several domain-specific cognitive functions on-trial, which largely persisted through up to 4 years post-trial. The strongest statistical evidence was for global cognitive function: 0.07 standard deviation decrements both on-trial (p=0.007) and post-trial (p=0.01). Among domain specific scores, the mean relative decrements were slightly smaller, were less significant, and tended to be larger for CEE-alone therapy.
CEE-based therapies, when initiated after age 65 years, produce a small broad-based decrement in cognitive function that persists after their use is stopped. The differences in cognitive function however are small and would not be detectable or have clinical significance for an individual woman. Differences in effects among cognitive domains suggest that more than one mechanism may be involved.