Vaginal Estrogen for Urinary Tract Infections

(TAPER Trial)

No longer 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests vaginal estrogen cream (Estradiol Cream) to prevent urinary tract infections (UTIs) in postmenopausal women who frequently experience them. Researchers aim to determine if applying a small amount of the cream near the urethra is as effective as the usual method of using more cream inside the vagina. Postmenopausal women with multiple UTIs in the past year might be suitable candidates for this study. As a Phase 2 trial, the research focuses on evaluating the treatment's effectiveness in an initial, smaller group of participants.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that vaginal estrogen is generally safe. Studies have found no increased risk of heart disease or cancer for those using it. This is encouraging for anyone considering it to help with urinary tract infections (UTIs). The estradiol cream used in this trial effectively reduced UTIs in postmenopausal women.

For those concerned about side effects, the evidence is reassuring. The estradiol cream does not appear to cause serious health issues. However, like any treatment, mild side effects might occur. It's important to weigh these against the benefits. Always consult a doctor to determine if it's suitable. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for urinary tract infections?

Most treatments for urinary tract infections (UTIs) traditionally involve antibiotics, which can lead to resistance issues. Researchers are excited about using estradiol cream because it offers a hormone-based approach, which is different from the usual antibiotic treatments. Specifically, applying estradiol cream either around the urethra or intravaginally may help strengthen the vaginal and urinary tract tissues, potentially reducing UTI recurrence by creating a less favorable environment for bacteria. This hormone therapy could provide a non-antibiotic option for preventing UTIs, which is particularly beneficial for those who experience frequent infections and are concerned about antibiotic resistance.

What evidence suggests that this trial's treatments could be effective for recurrent urinary tract infections?

Research has shown that vaginal estrogen can help lower the risk of repeated urinary tract infections (rUTIs) in postmenopausal women. In one study with 167 women, 67.7% experienced improvements or their symptoms completely disappeared when using vaginal estrogen. Estrogen helps restore the natural balance and health of the vaginal area, which can prevent infections. In this trial, participants will be assigned to one of two treatment arms: one group will receive intravaginal estrogen application, a method studied more extensively, while the other group will receive periurethral estrogen application. Researchers aim to determine if applying estrogen around the urethra (the opening where urine exits) can work just as well with less cream. However, no evidence currently shows that this new method is as effective as the traditional one. ^{6 7 8 9 10}

Who Is on the Research Team?

Stephanie W Zuo, MD

Principal Investigator

University of Pittsburgh Medical Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

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 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 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]

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]

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 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]

Citations

1.

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.

2.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/40169076

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.

3.

clinicaltrials.gov

clinicaltrials.gov/study/NCT05472779

Periurethral vs Intravaginal Estrogen for Prevention of ...

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 ...

4.

withpower.com

withpower.com/trial/phase-2-urinary-tract-infections-9-2022-311fd

Vaginal Estrogen for Urinary Tract Infections (TAPER Trial)

In a study of 167 postmenopausal women with recurrent urinary tract infections (rUTIs), 67.7% experienced improvement or resolution of symptoms with vaginal ...

5.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC7737516/

Vaginal estrogen therapy is associated with decreased ...

Vaginal estrogen therapy has been shown to decrease the risk of recurrent urinary tract infections in postmenopausal women, but the mechanism of action has not ...

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.

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.

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.

mayoclinic.org

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

Estradiol (vaginal route) - Side effects & dosage

Adults—10 micrograms (mcg) or one insert into the vagina once a day for 2 weeks, followed by one insert 2 times a week. Children—Use is not recommended. For ...

10.

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.