Fig. 4.
The effect of estrogen on the risk of cognitive decline or dementia varies with age at the time of treatment, type of menopause, and stage of menopause (relative risk estimated by an odds ratio or a hazard ratio and 95% confidence intervals, logarithmic scale). Women with ovarian conservation have a reduced long-term risk of cognitive decline or dementia compared to women who underwent bilateral oophorectomy before menopause (most commonly before age 50 years). Treatment with estrogen in the early postmenopausal stage (most commonly at ages 50–60 years) is associated with a reduced long-term risk of cognitive decline or dementia. However, initiation of estrogen treatment in the late postmenopausal stage (ages 65–79 years) is associated with an increased risk of cognitive impairment or dementia. CEE = conjugated equine estrogen; HR = hazard ratio; MPA = medroxyprogesterone acetate; OR = odds ratio; WHI = Women’s Health Initiative Study (Yaffe et al., 1998; Waring et al., 1999; Hogervorst et al., 2000; LeBlanc et al., 2001; Zandi et al., 2002; Shumaker et al., 2003; Shumaker et al., 2004; Rocca et al., 2007) [Modified from W.A. Rocca et al., Neurodegenerative Dis 2010;7:163–166]. aThese three publications were meta-analyses.