Hormone therapy and stroke: is it all about timing?

Although women have a lower incidence of stroke than men in most age groups, women have an overall increased lifetime risk of stroke. Women also have unique risk factors for stroke, including the menopausal transition, the existence of debilitating vasomotor symptoms for some women, and the issues related to hormonal treatment for those symptoms. Although the initial studies of hormone therapy (HT) use in postmenopausal women suggested significant protection against heart disease, there was no obvious protection against stroke. Randomized trials of HT for secondary prevention showed a lack of benefit for both heart disease and stroke, and the suggestion of some early risk after initiation. However, the Women's Health Initiative (WHI), a primary prevention study of the impact of HT on women aged 50 to 79 years, showed an increased risk of stroke, whether the HT was estrogen alone or estrogen combined with progestin. Therefore, HT is not recommended for stroke prevention, and it appears to cause harm. The reason for this increased stroke risk is not understood, but some have suggested that the initiation of HT closest to the time of menopausal transition should decrease the risk. Although there was a lower risk of heart disease when HT was initiated earlier, the risk appeared to be the same for stroke regardless of the timing. This was shown in both the WHI and the Nurses' Health Study cohorts. Therefore, more research is needed to understand the mechanisms for the increased stroke risk and to identify those who may be at risk because of HT for vasomotor symptoms, atrophic vaginitis, or osteoporosis, the three remaining indications for HT use in women. Trials are under way to assess the intermediate outcomes of HT on subclinical vascular disease in perimenopausal/early postmenopausal women.