Estrogen And Stroke Risk

Eighteen years ago this month the National Institutes of Health (NIH) announced that it would sponsor a landmark study to examine women and cardiovascular disease. Known as the Women’s Health Initiative (WHI), the study enrolled more than 161,000 women. By 2004 however, the government had ended two arms of the study involving estrogen after researchers found it posed a small but detrimental risk for stroke to postmenopausal women taking the hormone. The findings caught many members of the scientific community by surprise as estrogen had previously been shown to protect the brain from stroke in animal models.

Stroke, also known as a brain attack, is America’s third leading cause of death. It typically occurs when blood flow to the brain is blocked, usually due to a clogged artery. When a stroke occurs, brain damage can result, especially in the area known as the hippocampus, thought to be the site for memory, memory loss, and learning. Despite the possible link between estrogen and stroke many women continue to take the hormone to manage their menopausal symptoms.

Does Estrogen Replacement Need to Occur Before Menopause to Protect the Brain?

Researchers at the Medical College of Georgia (MCG), along with collaborators at the North China Coal Medical University in Tangshan, China, and the University of Texas Health Sciences Center in San Antonio, have taken the understanding between the hormone and the risk, and advanced scientific understanding. Their new study, using animals, finds that (1) estrogen clearly and strongly protects the hippocampus after stroke, thereby reducing some aspects of stroke-related brain damage; (2) that the hippocampus region of the brain becomes hypersensitive after a stroke if it has gone without sufficient levels of estrogen for long periods of time (and this study is the first to observe this transformation); (3) that long periods of low estrogen makes the hippocampus insensitive to estrogen protective effects, though the tissues of the uterus retain their sensitivity to estrogen; and (4) estrogen significantly inhibits activation of a key membrane enzyme NADPH oxidase, which produces reactive free radical molecules that cause brain damage following stroke.

The study provides support for the theory that there may be a “critical period” for beneficial protective effect of estrogen on the brain e.g. that of estrogen replacement may need to be initiated prior to or at the time of menopause if estrogen is to protect the brain. Additional studies will need to confirm the findings. – APS