Table 3.
Large randomized, double-blind, placebo-controlled trials of hormone therapy in older women without dementia: cognitive outcomesa
| Reference | Age, mean or range |
Menopause typeb |
Number | Duration | Episodic memory |
Other cognitive outcomes |
|---|---|---|---|---|---|---|
| Grady et al. (2002)c | 67 y | Both | 1063 | 4 y | NS | Most NSd |
| Rapp et al. (2003)e | 65–79 y | Natural | 4381 | 4 y | — | NS |
| Espeland et al. (2004)e | 65–79 y | Surgical | 2808 | 5 y | — | NS |
| Viscoli et al. (2005)c | 70 y | Both | 461 | 3 y | NS | NS |
| Almeida et al. (2006) | 74 y | Surgical | 115 | 5 mo | NS | NS |
| Resnick et al. (2006)e | 71 y | Natural | 1416 | 4 y | Variablef | NS |
| Yaffe et al. (2006) | 67 y | Natural | 417 | 2 y | NS | NS |
| Resnick et al (2009)e | 74 y | Surgical | 886 | 6 y | NS | Most NSg |
Trials with sample size of at least 100, mean age of at least 60 years, trial duration of at least 1 month, and an objective measure of cognitive outcome. Active treatment was with conjugated equine estrogens (Grady et al., 2002; Rapp et al., 2003; Espeland et al., 2004; Resnick et al., 2006; Resnick et al., 2009), oral estradiol (Viscoli et al., 2005; Almeida et al., 2006), or very low-dose transdermal estradiol (Yaffe et al., 2006). Some women randomized to an estrogen also received a progestagen (medroxyprogesterone acetate) (Rapp et al., 2003; Resnick et al., 2006).
Surgical menopause based on hysterectomy status.
Participants had coronary heart disease (Grady et al., 2002) or cerebrovascular disease (Viscoli et al., 2005).
Significant difference in verbal fluency favored the placebo group; other cognitive outcomes did not differ.
Women’s Health Initiative Memory Study of women with (Rapp et al., 2003; Resnick et al., 2006) or without (Espeland et al., 2004; Resnick et al., 2009) a uterus. Rapp et al. (2003) and Espeland et al (2004) report global cognition on the Modified Mini-Mental State examination. In the Women’s Health Initiative Study of Cognitive Aging, Resnick et al. (2006, 2009) report more detailed cognitive analyses on subsets of women included in reports of Rapp et al. (2003) and Espeland et al. (2004).
Based on annual rates of change, significant differences on verbal memory favored the placebo group, and significant differences on nonverbal memory favored the hormone group.
Significant differences on a mental rotation task 3 years after treatment randomization favored the placebo group, but thereafter the estrogen group showed greater improvement over time.
NS = non-significant probability p > 0.05