Postmenopausal HT Early observational evidence suggested a potential benefit of HT on cerebrovascular disease248 ; however, even as early as 2002, evidence was emerging that HT may have detrimental effects. A review of 29 observational studies found no clear evidence that HT use benefited stroke risk in postmenopausal Subsequent randomized clinical trials for both the primary and secondary prevention of stroke in women ran- domized to HT have been universally negative (Table 9). Two large clinical trials examined women with established vascular disease: the Heart and Estrogen/Progestin Replacement Study (HERS) and Women s Estrogen for Stroke Trial (WEST).250,251 Stroke events (including any stroke and IS) were similar for women allocated to an estrogen or to placebo. Findings from the WHI HT trials were reported soon after those from HERS and WEST. The multicenter WHI random- ized women into groups according to use of conjugated equine estrogen (CEE) and medroxyprogesterone or CEE alone, based on hysterectomy status.253 256 These women, unlike those in previous randomized trials, did not have documented vascular disease (no self-reported history of acute MI, stroke, or TIA in the previous 6 months); however, they were considerably older than women in previous observational trials, with a mean age of 63 years. Additional analyses of the WHI focused on specific subgroups of women to determine those at particularly high risk; the subgroups were outlined in previousAHA guidelines.19 The risk of stroke with CEE was limited to IS (HR, 1.55; 95% CI, 1.19 2.01) and not hemorrhagic stroke (HR, 0.64; 95% CI, 0.35 1.18). There was no difference based on stroke pathogenic subtype, severity, or mortality. Women with no prior history of CVD were at higher risk (HR, 1.73; 95% CI, 1.28 2.33) than women with a prior history (HR, 1.01; 95% CI, 0.58 1.75). 