Mouse menopause model sheds light on UTIs in post-menopausal women

Researchers from Washington University School of Medicine, St. Louis, show that reservoirs of uropathogenic E. coli within the bladder exist in higher numbers post-menopause than pre-menopause in a mouse model, a finding that could help explain the greater prevalence of urinary tract infections in post-menopausal women. They also found that estrogen supplementation reduced the numbers of such reservoirs dramatically. The research was published online ahead of print in the journal Infection and Immunity.

Urinary tract infections (UTIs) afflict an estimated 13 million American women annually. Post-menopausal women are especially vulnerable to UTIs. The high incidence of UTIs in post-menopausal women has long been thought related to the menopausal fall in estrogen levels.

However, "estrogen therapy to help limit or prevent recurrent or chronic UTIs has not been consistently shown to be effective in reducing the burden of infections in this population," says Indira Mysorekar, a researcher on the study. "Given the increasing incidence of multidrug resistant bugs and the high incidence of UTIs in older women, it is vital that we fully understand the dynamics of estrogen interaction with uropathogenic Escherichia coli, and the course of UTIs, and model these to determine how they might intersect."

Uropathogenic E. coli also damage the bladder, says Mysorekar. "To repair the damage, new cells are produced that turn into specialized cells which make up the new bladder barrier," she says. "In the absence of estrogen," as in post-menopausal women, "this repair process was severely disrupted."

Among other things, abnormally elevated levels of immune system cytokines may damage bladder cells. In the mouse menopause model, "the cytokine levels are very high," she says. However, the researchers found that estrogen supplementation can reduce the levels of cytokines, as well as the infectious reservoirs to levels found pre-menopausally, mitigating the infection and the resulting damage.

The goal of the current research was "to develop a definitive model of UTIs in menopause, to understand both the effect of loss of estrogen on the course of infection, and to determine whether estrogen therapy would be effective," says Mysorekar.

"The long term goal of my lab is to identify the molecular and genetic pathways that govern the estrogenic regulation of normal bladder function, and how it is altered during bladder disease and in menopause," says Mysorekar. "Our findings lay the groundwork for exploring the mechanism of estrogenic action and for testing hormone therapy efficacy in our animal model, and eventually in humans."

UTI symptoms include frequent urination, often accompanied by a burning sensation, cloudy, bad-smelling urine, and pelvic pain. They can be dangerous if they spread to the kidneys.
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Formal publication of the article is scheduled for the March 2013 issue of Infection and Immunity.