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Estrogen May Offer Protection Against Delirium
Delirium is common among women with urinary tract infections (UTIs)—especially those who have experienced menopause. According to a 2019 study in Menopause Review, more than 50% of postmenopausal females develop recurrent UTIs.
Investigators from Cedars-Sinai, working with laboratory mice, have been able to prevent symptoms of UTI-induced delirium with estrogen.
“I think it is a major step toward a clinical trial of estrogen in human patients with UTIs,”
said Shouri Lahiri, MD, director of the Neurosciences Critical Care Unit and Neurocritical Care Research at Cedars-Sinai and senior author of the study published in Journal of Neuroinflammation.
In previous studies, Lahiri’s team found a connection between delirium and a protein called interleukin 6 (IL-6). A UTI causes this protein to travel through the blood to the brain, causing symptoms such as disorientation and confusion. Estrogen is a known suppressor of that protein, so the investigators designed experiments to test its effects on UTI-induced delirium.
The researchers compared pre- and “postmenopausal” mice with UTIs and observed their behavior in several types of specialized environments. They found that the mice in which menopause had been induced exhibited symptoms of delirium, such as anxiousness and confusion, while the others did not.
But after treating the “post-menopausal” mice with estrogen, levels of the damaging protein in the blood and delirium-like behavior were greatly reduced.
The investigators also looked at the direct effects of estrogen on neurons, using what Lahiri called a “UTI in a dish.”
“When we added estrogen to the cocktail, it mitigated the injury. So, we showed that there are at least two ways that estrogen helps reduce symptoms of delirium,” said Lahiri. It protects the neurons directly, as well as reduces IL-6 protein levels in the blood.
“This work is an important step in determining whether modulating immune response via estrogen replacement or other means is a more effective treatment,” said Nancy Sicotte, MD, chair of the Department of Neurology and the Women’s Guild Distinguished Chair in Neurology at Cedars-Sinai.
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