• Posted January 3, 2023

Could Estrogen Help Ease the Delirium That Can Come With UTIs?

Older women with urinary tract infections (UTIs) often experience delirium along with them, and researchers may have found a solution.

Estrogen, often given as part of hormone replacement therapy after menopause, may prevent these mental changes, according to researchers from Cedars-Sinai Medical Center in Los Angeles, who studied the condition in mice.

"There has been a resurgence of interest in hormone replacement therapy, and this study, which builds on our previous work, shows that it may be a tool to mitigate delirium," said senior author Dr. Shouri Lahiri, director of the Neurosciences Critical Care Unit and Neurocritical Care Research at Cedars-Sinai. "I think it is a major step toward a clinical trial of estrogen in human patients with UTIs."

Lahiri's team had previously linked delirium and an immune-regulating protein called interleukin 6 (IL-6).

When someone has a UTI or another medical issue, such as a lung injury, IL-6 can travel through the blood to the brain, causing symptoms such as disorientation and confusion.

Estrogen is known to suppress IL-6, which led this team to design experiments to test its effects on UTI-induced delirium.

Delirium is a lack of awareness of one's surroundings and is well known in the medical community.

"Even as a medical student, you know that if an older woman comes to the hospital and she's confused, one of the first things you check is whether the patient has a UTI," Lahiri said in a Cedars-Sinai news release.

To study this, the researchers observed the behavior of pre- and postmenopausal mice who had UTIs. The postmenopausal mice had symptoms of delirium, such as anxiousness and confusion. The other mice did not have these symptoms.

After researchers treated the mice with estrogen, symptoms of delirium were greatly reduced. The behavioral differences were not related to UTI severity, Lahiri said.

The researchers also looked at the direct effects of estrogen on neurons.

"We exposed individual neurons to an IL-6 inflammation cocktail to create UTI-like injury," Lahiri said, calling it "UTI in a dish."

"But 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. It reduces IL-6 levels in the blood and protects the neurons directly,"he said.

Before conducting a clinical trial, researchers would need to identify which patients with UTIs are most likely to experience delirium and at what point estrogen treatment might be most effective. It's not clear how estrogen acts to protect neurons. Results of animal studies often differ in people.

"Currently, it is common practice to treat UTI-induced delirium using antibiotics, even though there are no clinical trials that indicate this practice is effective and it is not supported by clinical practice guidelines," said Dr. Nancy Sicotte, chair of neurology at Cedars-Sinai.

"This work is an important step in determining whether modulating immune response via estrogen replacement or other means is a more effective treatment," she said in the release.

Having an effective treatment for delirium could be of long-term importance, Lahiri said. Delirium is a known risk factor for long-term mental impairments, such as Alzheimer's disease and related dementia.

Results were recently published in the peer-reviewed journal Scientific Reports.

More information

The U.S. Centers for Disease Control and Prevention has more on urinary tract infection.

SOURCE: Cedars-Sinai, news release, Dec. 8, 2022