The risk of stroke in postmenopausal women receiving hormonal therapy.

Stroke affects one in five women and is the third leading cause of death in the United States. The incidence increases with age, and the number of females experiencing a stroke is similar to the number of men, unlike in coronary disease, where the number of females suffering from the disease is lower before menopause and then slowly becomes equal to the number of men. There are multiple risk factors for stroke, but the most significant ones influencing the relationship between hormones and stroke are obesity, hypertension and smoking. There have been multiple studies looking at the relationship between hormones and stroke. Among observational studies, 21 have shown no effect, while six have shown a decreased risk and four studies, an increased risk. It is clear that the risk of stroke with hormones is only for ischemic and not hemorrhagic stroke. Among randomized trials, the Women's Health Initiative data, because of the study's size, have provided the greatest weight in meta-analytic reviews. Overall, an increase of 20-40% has been found, and, because of various confounding factors, it has been difficult to determine whether this is statistically significant, although several studies have confirmed this for all postmenopausal women treated. However, in younger women, aged 50-59 years, there is little evidence that the risk is significantly increased, and the overall background prevalence is low: 6-8/10 000 women/year. Recent studies have suggested the risk is not increased significantly with transdermal therapy and with lower doses, although use of progestogen does not appear to influence the risk assessment. There is lack of consistent data on whether early age of initiation of therapy affects the risk. Because this risk may pertain to younger postmenopausal women, and there is a very small risk of stroke reported for young women taking oral contraceptives, it is suggested that the small risk in younger women is through an inflammatory/thrombosis mechanism in susceptible women, rather than one of atherosclerosis, as with coronary disease. Nevertheless, in younger postmenopausal women, with a lower baseline prevalence rate, even if there is a 40% increased risk, the attributable risk would result in 1-2 additional cases/10 000 women/year, which would be considered a very rare event.