Vaginal Estrogen for Urinary Tract Infections

(PRUVE Trial)

Overseen By Susan Tuddenham, MD

Age: 18+

Sex: Female

Trial Phase: Phase 4

Sponsor: Johns Hopkins University

Must be taking: Vaginal estrogen

Must not be taking: Antibiotics

Disqualifiers: Antibiotic prophylaxis, Immune compromise, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

50 Participants Needed

Trial Summary

What is the purpose of this trial?

Among postmenopausal women who suffer from recurrent urinary tract infections (UTI), vaginal estrogen therapy prevents UTI recurrences for 50% of sufferers. This research will investigate why some women benefit but others do not, focusing on (a) the effects of vaginal estrogen therapy on the bacteria that inhabit the vagina and bladder, (b) its influence on immune responses in both compartments, and (c) the extent to which those changes are critical to successful UTI prevention. The findings will be a first step in the development of more effective strategies to prevent UTI, one of the most common and costly benign urologic conditions.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are on antibiotics to prevent UTIs or have used vaginal or systemic estrogen in the past 6 months.

What data supports the effectiveness of the drug Vaginal Estradiol Tablets for preventing urinary tract infections?

Research shows that vaginal estrogen, including estradiol, can help prevent recurrent urinary tract infections in postmenopausal women. Studies indicate that using vaginal estrogen is more effective than a placebo, with significant benefits observed in reducing infections. ^{1 2 3 4 5}

Is vaginal estrogen safe for humans?

Research on low-dose vaginal estrogen, such as 17beta-estradiol tablets, suggests it is generally safe for treating conditions like postmenopausal atrophic vaginitis (thinning and inflammation of the vaginal walls). ^{2 3 4 6 7}

How is the drug Vaginal Estradiol Tablets different from other treatments for urinary tract infections?

Vaginal Estradiol Tablets are unique because they deliver estrogen directly to the vaginal area, which can help restore the natural balance of bacteria and reduce the risk of urinary tract infections, especially in postmenopausal women. This local application is different from systemic estrogen treatments, which affect the whole body and are not recommended for this purpose. ^{1 2 4 6 8}

Research Team

Victoria Handa, MD MHS

Principal Investigator

Johns Hopkins University

Eligibility Criteria

This trial is for postmenopausal women aged 55 or older who have had at least 3 UTIs in the past year or 2 within the last 6 months, with one confirmed by urine culture. It's not for those currently on antibiotics to prevent UTIs, those with contraindications to vaginal estrogen, recent antibiotic use, complicated recurrent UTI due to other health issues.

Inclusion Criteria

I am a woman aged 55 or older and have been postmenopausal for at least 1 year.

I have had 3 UTIs in the last year or 2 in the last 6 months, with at least one confirmed by a lab test.

Exclusion Criteria

I cannot use vaginal estrogen due to health risks and haven't used any estrogen treatments in the last 6 months.

I am a woman with frequent UTIs and have conditions like immune issues or use a catheter.

I am a woman currently with a UTI or have taken antibiotics in the last 2 weeks.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive vaginal estrogen therapy to assess its impact on urogenital microbiota and immune responses

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, focusing on UTI recurrence and microbiota changes

12 weeks

Treatment Details

Interventions

• Vaginal Estradiol Tablets

Trial Overview The study tests if vaginal estradiol tablets can prevent recurrent urinary tract infections in postmenopausal women. It examines how this treatment affects vaginal and bladder bacteria and immune responses to understand why it helps some women but not others.

Participant Groups

Group I: Vaginal estrogen therapy Experimental Treatment 1 Intervention

Participants receive Vaginal estrogen therapy.

Who Is Running the Clinical Trial?

Johns Hopkins University

Lead Sponsor

Trials

2,366

Recruited

15,160,000+

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Collaborator

Trials

2,513

Recruited

4,366,000+

University of Maryland

Collaborator

Trials

171

Recruited

325,000+

Findings from Research

In a study of 167 postmenopausal women with recurrent urinary tract infections (rUTIs), 67.7% experienced improvement or resolution of symptoms with vaginal estrogen cream alone, indicating its efficacy as a first-line treatment.

Women with urinary incontinence were found to be 2.3 times more likely to require additional therapies for rUTIs, highlighting the importance of this condition as a risk factor in treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vaginal Estrogen as First-Line Therapy for Recurrent Urinary Tract Infections in Postmenopausal Women and Risk Factors for Needing Additional Therapy. Chang, E., Kent, L., Prieto, I., et al.[2022]

In a study of 45 postmenopausal women, the use of intravaginal estrogen cream significantly reduced the incidence of recurrent urinary tract infections (UTIs) compared to an oral antibiotic treatment, with only 2 out of 27 women in the estrogen group experiencing UTIs versus 12 out of 15 in the antibiotic group.

The estrogen cream not only decreased UTI occurrences but also improved vaginal health indicators, such as the presence of Lactobacilli and vaginal cell maturation, suggesting a beneficial effect on vaginal flora and overall health in postmenopausal women.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Prevention and treatment of recurrent urinary system infection with estrogen cream in postmenopausal women]. Xu, R., Wu, Y., Hu, Y.[2014]

In a study of 5,638 women with hypoestrogenism, prescribing vaginal estrogen led to a significant reduction in urinary tract infections (UTIs), with the frequency dropping from an average of 3.9 to 1.8 infections per year, representing a 51.9% decrease.

Factors such as older age, higher baseline UTI frequency, urinary incontinence, urinary retention, and diabetes were linked to an increased risk of UTIs after starting vaginal estrogen, while surprisingly, women with higher medication adherence had a smaller reduction in UTI frequency, suggesting potential confounding factors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of vaginal estrogen for recurrent urinary tract infection prevention in hypoestrogenic women. Tan-Kim, J., Shah, NM., Do, D., et al.[2023]

A systematic review of seven studies, including four randomized trials, found insufficient evidence to determine if vaginal estrogens effectively reduce the risk of urinary tract infections in postmenopausal women.

The overall certainty of the evidence regarding the effectiveness of vaginal estrogens for preventing urinary infections was rated as very low, indicating that more research is needed to draw definitive conclusions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Are vaginal estrogens effective for preventing urinary tract infection in postmenopausal women? Canales, JP., Castro, V., Rada, G.[2018]

In a study involving 325 postmenopausal women, low-dose 17beta-estradiol vaginal tablets significantly improved symptoms of atrophic vaginitis within just two weeks of treatment.

The treatment was found to be safe, with minimal adverse reactions reported, and no cases of abnormal endometrial thickness or treatment interruptions due to bleeding, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Local estrogen replacement therapy in postmenopausal atrophic vaginitis: efficacy and safety of low dose 17beta-estradiol vaginal tablets. Mainini, G., Scaffa, C., Rotondi, M., et al.[2022]

A review of 8 studies on systemic estrogen therapy for preventing recurrent urinary tract infections (rUTI) in postmenopausal women found that none met all criteria for ideal research, indicating a lack of strong evidence for its efficacy.

Current guidelines recommend vaginal estrogen for rUTI prevention, but the evidence for systemic estrogen is inconclusive and based on studies with significant methodological limitations, highlighting the need for further research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of systemic estrogen for preventing urinary tract infections in postmenopausal women. Fox, KA., Lokken, EM., Reed, SD., et al.[2023]

References

1. United States pubmed.ncbi.nlm.nih.gov

Vaginal Estrogen as First-Line Therapy for Recurrent Urinary Tract Infections in Postmenopausal Women and Risk Factors for Needing Additional Therapy. [2022]

2. China pubmed.ncbi.nlm.nih.gov

[Prevention and treatment of recurrent urinary system infection with estrogen cream in postmenopausal women]. [2014]

3. United States pubmed.ncbi.nlm.nih.gov

Vaginal Estrogen for the Prevention of Recurrent Urinary Tract Infection in Postmenopausal Women: A Randomized Clinical Trial. [2021]

4. United States pubmed.ncbi.nlm.nih.gov

Efficacy of vaginal estrogen for recurrent urinary tract infection prevention in hypoestrogenic women. [2023]

5. England pubmed.ncbi.nlm.nih.gov

A systematic review of estrogens for recurrent urinary tract infections: third report of the hormones and urogenital therapy (HUT) committee. [2019]

6. Chile pubmed.ncbi.nlm.nih.gov

Are vaginal estrogens effective for preventing urinary tract infection in postmenopausal women? [2018]

7. Singapore pubmed.ncbi.nlm.nih.gov

Local estrogen replacement therapy in postmenopausal atrophic vaginitis: efficacy and safety of low dose 17beta-estradiol vaginal tablets. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Evaluation of systemic estrogen for preventing urinary tract infections in postmenopausal women. [2023]