Woman holding birth control pills in hand to illustrate to impact of estrogen exposure on stroke risk after the menopause
Credit: Rattankun Thongbun/Getty Images

Post-menopausal women with a higher cumulative exposure to estrogen have reduced risk for stroke compared to those with lower exposure, show results from a China Kadoorie Biobank study.

Taking factors such as reproductive life span (from first menstruation to menopause), use of oral contraceptives, number of births, and length of breastfeeding into account, Peige Song, a researcher at the Zhejiang University School of Medicine in Hangzhou, China, and colleagues found those in the highest quartile for estrogen exposure had a significant reduction in stroke risk compared with those in the lowest quartile.

“Our study suggests that higher estrogen levels due to a number of reproductive factors, including a longer reproductive life span and using hormone therapy or contraceptives, are linked to a lower risk of ischemic stroke and intracerebral hemorrhage,” said Song, lead author of the paper describing the work in the journal Neurology, in a press statement.

“These findings might help with new ideas for stroke prevention, such as considering screenings for people who have a short lifetime exposure to estrogen.”

Every year, more than 795,000 people in the U.S. have a stroke and in 2020 one in six deaths from cardiovascular disease was due to stroke. Estrogen is known to impact cardiovascular disease risk, including stroke, and is largely thought to have a protective effect. This is thought to be one factor contributing to lower numbers of cardiovascular events in women than men before the menopause.

Earlier studies have mostly focused on reproductive lifespan as a measurement of estrogen exposure, but a number of other factors such as use of oral contraceptives or hormone therapy during or after menopause can also impact this measure.

The current study used data collected from 122,939 post-menopausal women aged 40 to 79 years who had not experienced a stroke at the beginning of the study (2004-2008) and who were participating in the China Kadoorie Biobank study.

The researchers assessed estrogen exposure using a combination of reproductive lifespan, endogenous estrogen exposure, and total estrogen exposure. Cases of stroke, ischemic stroke, intracerebral hemorrhage and subarachnoid hemorrhage, were monitored using a disease registry system and health insurance data between 2004 and 2015.

When split into quartiles, the longest reproductive lifespan group was 36 years or more and the shortest was 31 years or less. After adjusting for stroke risk factors such as age, smoking, physical activity and high blood pressure, women with the longest reproductive lifespan had a five percent lower risk of all types of strokes, a five percent lower risk of ischemic stroke and a 13 percent lower risk of intracerebral hemorrhage than those with the shortest reproductive lifespan.

A similar, albeit stronger, trend was seen for endogenous estrogen exposure, and total estrogen exposure, which take into account factors such as pregnancy, oral contraceptive use and breastfeeding, as well as hormone therapy. For example, women in the highest quartile for total estrogen exposure had a 13 percent reduced risk for all stroke types compared with the lowest quartile.

“Estrogen exposure throughout life could potentially be a useful indicator of a person’s risk of different types of strokes following menopause,” said Song. “However, more research is needed on the biological, behavioral, and social factors that may contribute to the link between estrogen exposure and stroke risk across a woman’s lifespan.”

Also of Interest