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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines whether vaginal estrogen therapy, specifically Vaginal Estradiol Tablets, can prevent frequent urinary tract infections (UTIs) in postmenopausal women. Researchers aim to determine why the treatment benefits some women but not others by studying its effects on bacteria and immune responses in the vagina and bladder. Participants must be postmenopausal for at least a year and have a history of recurring UTIs, defined as at least three infections in the past year or two episodes within six months. As a Phase 4 trial, this research seeks to understand how this FDA-approved and effective treatment can benefit more patients.

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 is the safety track record for vaginal estrogen therapy?

Research has shown that vaginal estrogen is safe to use. Studies have found that it does not increase the risk of heart disease or cancer, supporting its safety. Specifically, past patients demonstrated that vaginal estrogen can help reduce urinary tract infections in postmenopausal women.

Some women might experience mild side effects like vaginal dryness or itching, but these are usually not serious. Most people tolerate the treatment well. Overall, vaginal estrogen is considered a safe option for preventing urinary tract infections in postmenopausal women. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Most treatments for urinary tract infections (UTIs) involve antibiotics, which can lead to resistance and disrupt the natural balance of bacteria in the body. Vaginal estradiol tablets offer a unique approach by using estrogen therapy to strengthen the vaginal lining and restore healthy bacteria, which can help prevent UTIs from recurring. Researchers are excited about this treatment because it targets the root cause of frequent UTIs in postmenopausal women by addressing hormonal changes, rather than just treating the symptoms with antibiotics. This method could provide a more sustainable and preventive solution to UTIs compared to traditional antibiotic use.

What is the effectiveness track record for vaginal estrogen therapy in preventing urinary tract infections?

Research has shown that vaginal estrogen can help reduce urinary tract infections (UTIs) in postmenopausal women. One study found that after starting this treatment, 55.3% of women had one or fewer infections over the next year, and 31.4% had no infections at all. This indicates that many women experienced fewer UTIs with the therapy. Additionally, vaginal estrogen has been linked to lower chances of serious issues like severe infections (sepsis) and death. These findings suggest that vaginal estrogen could be a promising way to prevent repeated UTIs in postmenopausal women. ^{2 6 7 8 9}

Who Is on the Research Team?

Victoria Handa, MD MHS

Principal Investigator

Johns Hopkins University

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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]

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 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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37178856/

Efficacy of vaginal estrogen for recurrent urinary tract ... During the 12 months after the index prescription, 55.3% of patients experienced ≤1 urinary tract infections, and 31.4% experienced no urinary tract infections.

2. ajog.org ajog.org/article/S0002-9378(23)00309-5/abstract

Efficacy of vaginal estrogen for recurrent urinary tract ... This study aimed to assess the association between vaginal estrogen prescription and the frequency of urinary tract infections over the following year.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05723601

Preference of Women With Recurrent Urinary Tract ... Vaginally applied estrogen has been shown to decrease the incidence of Recurrent Urinary Tract Infection (rUTI) in post-menopausal women.

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1551714425000874

Periurethral versus intravaginal application of vaginal ... Results from this trial will provide evidence regarding the effectiveness of intravaginal versus periurethral estradiol application for UTI prevention.

5. medscape.com medscape.com/viewarticle/sharp-drop-sepsis-mortality-when-older-women-use-vaginal-2025a1000a8n

Vaginal Estrogen Boosts Outcomes for Older Women ... Those who use have significantly lower rates of sepsis (19.4% vs 10.6%) and mortality (1.54% vs 0.42%), according to new data presented at the American ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6538478/

Vaginal estrogen use and chronic disease risk in ... Vaginal estrogen use was not associated with a higher risk of cardiovascular disease or cancer. Our findings lend support to the safety of vaginal estrogen use.

7. mayoclinic.org mayoclinic.org/drugs-supplements/estradiol-vaginal-route/description/drg-20075648

Estradiol (vaginal route) - Side effects & dosage Estradiol vaginal gel, insert, and ring are used to treat changes in and around the vagina (such as vaginal dryness, itching, and burning) ...

8. sciencedirect.com sciencedirect.com/science/article/pii/S0378512224002238

Efficacy and safety of an ultra-low-dose 0.005 % estriol ... Ultra-low-dose 0.005 % estriol vaginal gel is safe and effective in preventing recurrent urinary tract infections in postmenopausal women with genitourinary ...

9. acog.org acog.org/clinical/clinical-guidance/clinical-consensus/articles/2021/12/treatment-of-urogenital-symptoms-in-individuals-with-a-history-of-estrogen-dependent-breast-cancer

Treatment of Urogenital Symptoms in Individuals With a ... This document has been updated to review the safety and efficacy of newer hormonal treatment options as well as nonhormonal modalities.