Vaginal Estrogen for Urinary Tract Infections

(TAPER Trial)

Recruiting at 4 trial locations

Overseen By Stephanie W Zuo, MD, MSc

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: Mary Ackenbom

Must be taking: Vaginal estrogen

Must not be taking: Oral estrogen, Antibiotics

Disqualifiers: Vaginal stenosis, Catheter use, 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: 6 months

114 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires that you stop using any vaginal or oral estrogen products and daily antibiotics before participating. If you are using these, you will need to discontinue them to be eligible for the study.

What data supports the effectiveness of the drug Estradiol Cream for preventing urinary tract infections in postmenopausal women?

Research shows that using vaginal estrogen, like Estradiol Cream, can help prevent recurrent urinary tract infections in postmenopausal women. A meta-analysis found that estrogen treatment significantly reduced the risk of infections compared to a placebo, especially when applied vaginally. ^{1 2 3 4 5}

Is vaginal estrogen cream safe for humans?

Vaginal estrogen cream has been studied for use in postmenopausal women to prevent urinary tract infections, and it is generally considered safe for this purpose. However, the research is mostly based on small studies, so while it is commonly used, it's always best to discuss any concerns with your doctor. ^{1 2 3 4 6}

How does the drug Estradiol Cream differ from other treatments for urinary tract infections?

Estradiol Cream is unique because it is a vaginal estrogen treatment specifically used to prevent recurrent urinary tract infections in postmenopausal women by addressing estrogen deficiency, which can alter vaginal flora and increase infection risk. Unlike systemic estrogen treatments, it is applied directly to the vaginal area, which is considered more effective for this purpose. ^{1 2 3 4 7}

What is the purpose of this trial?

Due to rising antibiotic resistance, there has been a focus on non-antibiotic prophylactic measures for postmenopausal patients with recurrent urinary tract infections (rUTI), one of which is the safe and efficacious option of vaginal estrogen therapy. Standard application of vaginal estrogen cream entails intravaginal application of the cream twice a week, but some providers counsel patients with rUTI to apply a small, pea-sized amount to the periurethral area. This ideally reduces the amount of vaginal estrogen used while attaining a similar effect. However, to date, there is no data to prove that the periurethral technique of application is similar or non-inferior to intravaginal application in preventing UTI.

Research Team

Stephanie W Zuo, MD

Principal Investigator

University of Pittsburgh Medical Center

Eligibility Criteria

This trial is for postmenopausal women who've had at least 2 UTIs in the last 6 months or 3 in a year, and are recommended vaginal estrogen to prevent more UTIs. They shouldn't be currently using any estrogen products, have significant vaginal narrowing, bladder stones, risk of estrogen-dependent cancer, or conditions preventing them from applying the cream themselves.

Inclusion Criteria

I am postmenopausal, meeting the age or lab criteria if I had a hysterectomy.

I have had 2 or more UTIs in 6 months or 3 or more in a year.

I stopped using vaginal estrogen over 3 months ago.

Exclusion Criteria

Inability to use vaginal applicator and without caregiver who can administer (eg. provider-managed pessary use, significant arthritis)

I am currently using vaginal or oral estrogen products.

I am unable to give my own consent for medical procedures.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either periurethral or intravaginal application of estradiol cream twice a week for 6 months

6 months

Regular visits for monitoring and assessment

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Estradiol Cream

Trial Overview The study compares two ways of using estradiol cream to prevent recurrent urinary tract infections: periurethral (around the urethra) versus intravaginal application. It aims to determine if applying less cream around the urethra is as effective as the standard intravaginal method.

Participant Groups

Group I: Periurethral Estrogen Application Experimental Treatment 1 Intervention

Periurethral application of 0.5 gram estradiol cream at bedtime twice a week for 6 months

Group II: Intravaginal Estrogen Application Active Control 1 Intervention

Intravaginal application of 1 gram estradiol cream at bedtime twice a week for 6 months

Who Is Running the Clinical Trial?

Mary Ackenbom

Lead Sponsor

Trials

1

Recruited

110+

Stephanie Wang Zuo

Lead Sponsor

Trials

1

Recruited

110+

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]

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 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]

In a double-blind, randomized trial involving 72 postmenopausal women over 60 years old, oral oestriol (3 mg per day) did not show a significant advantage over placebo in preventing recurrent urinary tract infections.

Both oestriol and placebo improved urinary symptoms, suggesting that while oestriol may not be effective for this specific purpose, it could still provide some symptomatic relief.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low dose oestrogen prophylaxis for recurrent urinary tract infections in elderly women. Cardozo, L., Benness, C., Abbott, D.[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. Chile pubmed.ncbi.nlm.nih.gov

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

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. England pubmed.ncbi.nlm.nih.gov

Low dose oestrogen prophylaxis for recurrent urinary tract infections in elderly women. [2022]

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

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