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6.25.2013

Miller School’s UTI Expert Finds Promising Avenues for Research in New Study

A new study further supporting the use of topical vaginal estrogen therapy to prevent recurrent urinary tract infections (UTIs) in postmenopausal women takes “an important step forward” and suggests intriguing new avenues for research on the common bacterial infection that afflicts millions of women every year, according to an editorial in the journal Science Translational Medicine co-authored by the Miller School’s Thomas M. Hooton, M.D.

One of the nation’s leading clinical authorities on UTI, Hooton, professor of clinical medicine and Associate Chief of Staff for the Medical Service at the Miami VA Healthcare System, was invited with Scott J. Hultgren, Ph.D., a basic scientist at Washington University whose work with a mouse model of UTI led to important new insights into the pathophysiology of UTI, to weigh in on the study published June 19 in the prestigious journal of The American Association for the Advancement of Science.

Their editorial, “Estrogen and Recurrent UTI: What Are the Facts?” was published in the same issue.

“Topical vaginal estrogens are often used in postmenopausal women with recurrent UTI, based on studies that show significant benefit in some women,” Hooton explained. “The new study we discuss in our editorial attempts to describe the mechanisms underlying this effect. We summarize what we know about UTI pathogenesis and how this information furthers our knowledge.”

Conducted by researchers at the Karolinska Institute in Stockholm, Sweden, the study, “Estrogen Supports Urothelial Defense Mechanisms,” investigated the influence of supplemental estrogen on urinary tract, or urothelial, cells from menstruating and postmenopausal women before and after a two-week period of estrogen supplementation. The investigators found that estrogen induced the expression of antimicrobial peptides, enhancing the antimicrobial capacity of the urothelium and restricting bacterial multiplication. In addition, estrogen prevented excessive loss of superficial cells during infection, thus maintaining the integrity of the epithelial barrier to infection.

The Swedish investigators also studied UTIs in mice whose ovaries were surgically removed and found that ovariectomy resulted in higher bacterial burdens in the bladder, compared with sham-operated mice, at 24 hours after infection.

In their commentary, Hultgren and Hooton noted that millions of women suffer from recurrent UTI, with suboptimal clinical management strategies and a global emergence of multidrug-resistant bacteria, making it imperative to pursue targeted, alternative, non-antibiotic strategies. They called the translational data from postmenopausal women undergoing estrogen supplementation “a real strength” of the Swedish study, and said “this approach should be used to study the expression of other factors important for mucosal defense in UTI.”

“With all the therapeutic possibilities, the role of estrogen in modulating mucosal defense and microbial invasion pathways merits further study in both animals and people,” they concluded.

Also contributing to the editorial was first author Thomas J. Hannan, D.V.M., Ph.D., research instructor of pathology and immunology at Washington University.

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