In a nested case-control study examining patients in general practices in the United Kingdom that included 15710 cases of stroke and almost 60000 randomly selected, matched control subjects from women aged 50 to79 years, transdermal estradiol was not associated with an increased risk of stroke, whereas oral estro- gens significantly increased stroke risk.272 Importantly, dose effects, even from transdermal use, were seen in this popu- lation, because low-dose products that contained 50 g of estrogen did not increase stroke risk (rate ratio, 0.81; 95% CI, 0.62 1.05) compared with no use, but high-dose patches that contained >50 g did increase risk (rate ratio, 1.89; 95% CI, 1.15 3.11). Until randomized blinded studies are performed that demonstrate the safety of transdermal therapy, this treat- ment is not recommended for stroke prevention on the basis of available evidence, although this treatment is approved for relief of menopausal symptoms. Postmenopausal HT: Summary and Gaps An increased risk of stroke is associated with the tested forms of HT, which include CEE/medroxyprogesterone in standard formulations. A recent analysis and review of 9 random- ized controlled trials,273 a review of HT trials by Henderson and a Cochrane review that included 23 stud- all reached the conclusion that HT, in the formulations prescribed in prior studies, does not reduce stroke risk and may increase the risk of stroke. There are insufficient data to assess the risk of long-term HT use initiated in perimeno- pausal women or postmenopausal women <50 years of age; however, the data on this subject are often conflicting, and information regarding risk with newer HT regimens contin- ues to emerge. There is no benefit of raloxifene or tamoxifen for stroke prevention, and raloxifene may increase the risk of fatal stroke. Tibolone is also associated with an increased risk of stroke. 