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Estrogen May Protect Against Delirium

Estrogen May Protect Against Delirium

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Symptoms of delirium can be prevented with the use of estrogen, according to an in-vitro study in mice.

Highlights:
  • Delirium is a state of confusion with changes in behavior like lack of attention
  • Women going through menopause often have urinary tract infections, which can cause delirium //
  • A recent experimental study on mice shows that estrogen can protect menopausal women from having delirium
Women with urinary tract infections (UTIs) may suffer from delirium. In a recent study, researchers working with laboratory mice, have been able to prevent symptoms of the condition with estrogen, which is commonly used for hormone replacement therapy.
Delirium-like states can broadly be defined as acute confusion with behavioral impairments including, inattention, short-term memory impairment, and psychomotor agitation. UTI, along with delirium, is known to contribute to increased mortality, prolonged hospitalizations, and long-term cognitive impairment, particularly in those with pre-existing neurodegenerative pathologies. Advanced age coinciding with the postmenopausal period and lower levels of estrogen is a well-established risk factor for delirium in women, who are significantly more susceptible to developing recurrent UTIs (1 Trusted Source
Beyond Urinary Tract Infections (UTIs) and Delirium: A Systematic Review of UTIs and Neuropsychiatric Disorders.

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).

Estrogen is a steroid hormone associated with the female reproductive organs and is responsible for developing female sexual characteristics. Estrogen is often referred to as estrone, estradiol, and estriol. Of the previously mentioned forms of estrogen, estradiol is the most common form of estrogen hormone for hormone replacement therapy (HRT) in the treatment of symptoms of menopause (2 Trusted Source
Estrogen

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).

Researchers say that 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, and they think it is a major step toward a clinical trial of estrogen in human patients with UTIs.

Delirium and UTIs in Menopausal Women

It is important to look for UTIs in an older woman if she has delirium. In previous studies, researchers found a connection between delirium and an immune-regulating protein called interleukin 6 (IL-6). Events such as lung injury or UTI cause IL-6 to travel through the blood to the brain, causing symptoms such as disorientation and confusion. Estrogen is a known suppressor of IL-6, 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 (3 Trusted Source
17β-estradiol ameliorates delirium-like phenotypes in a murine model of urinary tract infection

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).

When they treated the mice with estrogen, levels of IL-6 in the blood and delirium-like behavior were greatly reduced. The behavioral differences were not related to UTI severity, as bacterial levels in the urine weren’t markedly different between the two groups. The investigators also looked at the direct effects of estrogen on neurons.

Estrogen Helps Reduce Delirium

Researchers exposed individual neurons to an IL-6 inflammation cocktail to create a UTI-like injury. 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 the symptoms of delirium. It reduces IL-6 levels in the blood and protects the neurons directly.

The exact mechanism of how estrogen acts to protect neurons is still questionable. And before conducting a clinical trial, researchers need to identify which patients with UTIs are most likely to experience delirium and at what point estrogen treatment might be the most effective.

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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. This work is an important step in determining whether modulating immune response via estrogen replacement or other means is a more effective treatment.

Effective treatment of delirium could be of long-term importance because it is a known risk factor for long-term cognitive impairments, such as Alzheimer’s disease and related dementias.

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References:
  1. Beyond Urinary Tract Infections (UTIs) and Delirium: A Systematic Review of UTIs and Neuropsychiatric Disorders. - (https://europepmc.org/article/MED/26554322)
  2. Estrogen - (https://www.ncbi.nlm.nih.gov/books/NBK538260/)
  3. 17β-estradiol ameliorates delirium-like phenotypes in a murine model of urinary tract infection - (https://www.nature.com/articles/s41598-022-24247-w)


Source-Medindia


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