As mentioned earlier, AD is more likely to develop in women older than 65 years than in their male counterparts,3,4 possibly due to reduced estrogen levels.5 The association between ERT/HRT and the risk for AD remains controversial, although most investigations suggest that ERT/HRT reduces the risk for AD (Figure 1). A recent meta-analysis35 of 14 studies reported an OR of 0.56 (95% CI, 0.46-0.68) for the relative risk for the development of AD. The results of the studies analyzed were heterogeneous, and poor recall of ERT/HRT use may have confounded the results. A major 1998 meta-analysis116 of the effect of ERT/HRT on the risk for the development of AD in postmenopausal women, which examined 8 case-control studies6,108- 114 and 2 prospective cohort studies,26,115 reported a summary OR of 0.71 (95% CI, 0.52-0.98) for the development of dementia among estrogen users. Both prospective cohort studies and 1 case-control study113 reported a significantly lower risk for dementia in women who had ever used estrogen. Of the remaining studies, 3 reported no significant increase among estrogen users,6,110,114 2 reported no difference in risk,112,113 and 2 found no significant increased risk for dementia among estrogen users compared with nonusers.108,109 Because of significant heterogeneity in the findings, which may be attributable to study design, a separate analysis was performed of the 2 study types. The summary OR for the case-control studies was 0.80 (95% CI, 0.56-1.16) for diagnosis of AD; for the prospective studies, the summary OR was 0.48 (95% CI, 0.29-0.81). The 3 studies that investigated the relationship between the duration of estrogen use and protection against dementia found inconsistent results,6,26,115 although in a follow-up investigation of their earlier study, Paganini-Hill and Henderson25 found a decreased risk among long-term users of ERT.