Long-term Effects on Cognitive Trajectories of Postmenopausal Hormone Therapy in Two Age Groups.

Background: Postmenopausal hormone therapy may have long-term effects on cognitive function depending on women's age.

Methods: Postintervention follow-up was conducted with annual cognitive assessments of two randomized controlled clinical trial cohorts, beginning an average of 6-7 years after study medications were terminated: 1,376 women who had enrolled in the Women's Health Initiative when aged 50-54 years and 2,880 who had enrolled when aged 65-79 years. Women had been randomly assigned to 0.625mg/d conjugated equine estrogens (CEE) for those with prior hysterectomy (mean 7.1 years), CEE with 2.5mg/d medroxyprogesterone acetate for those without prior hysterectomy (mean 5.4 years), or matching placebos.

Results: Hormone therapy, when prescribed to women aged 50-54 years, had no significant long-term posttreatment effects on cognitive function and on changes in cognitive function. When prescribed to older women, it was associated with long-term mean (SE) relative decrements (standard deviation units) in global cognitive function of 0.081 (0.029), working memory of 0.070 (0.025), and executive function of 0.054 (0.023), all p < .05. These decrements were relatively stable over time. Findings did not vary depending on the hormone therapy regimen, prior use, or years from last menstrual period. Mean intervention effects were small; however, the largest were comparable in magnitude to those seen during the trial's active intervention phase.

Conclusions: CEE-based hormone therapy delivered near the time of menopause provides neither cognitive benefit nor detriment. If administered in older women, it results in small decrements in several cognitive domains that remain for many years.