Vaginal Estradiol Treatments for Recurrent Urinary Tract Infections

Overseen By Sachin Vyas, PhD

Age: 18+

Sex: Female

Trial Phase: Phase 4

Sponsor: Wake Forest University Health Sciences

Must be taking: Vaginal estrogen

Must not be taking: Prophylactic antibiotics, Systemic HRT

Disqualifiers: Interstitial cystitis, Urothelial cancer, 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

24 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether post-menopausal women with recurrent urinary tract infections (rUTIs) prefer a vaginal estradiol tablet or cream. The goal is to determine which form is easier for women to adhere to, as previous studies have shown that many find creams inconvenient. Participants will use one form for three months and then switch to the other for comparison. Women who have experienced at least three UTIs in the past year and are willing to try vaginal estrogen are suitable candidates for this trial. As a Phase 4 trial, this research aims to understand how the already FDA-approved treatment benefits 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 daily antibiotics or systemic hormone replacement therapy. If you have used vaginal estrogen recently, you must wait for a 1-month period without it before joining.

What is the safety track record for these treatments?

Research has shown that both estradiol vaginal cream and tablets are generally safe for post-menopausal women. Studies have found that using vaginal estrogen can reduce the frequency of urinary tract infections (rUTIs) in these women.

A detailed review found the estradiol vaginal cream effective with few side effects. Applying it directly to the skin likely has fewer systemic effects compared to oral estrogen.

The estradiol vaginal tablet also shows promise. Many patients prefer it, which aids in adherence to the treatment. Like the cream, the tablet is considered safe and has few side effects.

Both treatments alter the vaginal environment to lower infection risk, and current research suggests they are well-tolerated. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about the vaginal estradiol treatments for recurrent urinary tract infections (UTIs) because they offer a targeted approach that may enhance vaginal health and reduce infection rates. Unlike standard antibiotics that treat UTIs by eliminating bacteria, estradiol treatments focus on restoring the natural balance of the vaginal environment, potentially preventing infections from occurring in the first place. The use of estradiol cream and tablets provides flexibility in treatment options, allowing patients to choose a method that best fits their lifestyle while directly addressing hormonal imbalances that can contribute to recurrent UTIs.

What is the effectiveness track record for vaginal estradiol treatments for recurrent urinary tract infections?

This trial will compare two vaginal estradiol treatments for recurrent urinary tract infections. Research has shown that vaginal estrogen treatments can significantly reduce the number of repeat urinary tract infections (rUTIs) in post-menopausal women. Participants in one arm of this trial will start with vaginal estradiol cream. Studies found that about 55.3% of women using the cream had one or no infections over a year, and 31.4% had no infections at all, indicating a strong effect in reducing UTIs. Participants in the other arm will start with vaginal estradiol tablets, which have also been shown to lower the risk of these infections. One study noted a reduction of over 50% in infection rates with the tablets. Both treatments appear effective, offering hope for fewer infections and a better quality of life. ^{1 4 6 7 8}

Who Is on the Research Team?

Candace Parker-Autry, MD

Principal Investigator

Wake Forest University Health Sciences

Are You a Good Fit for This Trial?

This trial is for post-menopausal women aged 20-80, who have had recurrent UTIs and are willing to use vaginal estrogen for prevention. They shouldn't be on daily antibiotics, hormone replacement therapy, or have certain medical conditions like uncontrolled diabetes or active cancers sensitive to estrogen.

Inclusion Criteria

I have had 3 or more UTIs in the past year or 2 in the last 6 months, with at least one confirmed by culture.

I am not on daily antibiotics to prevent infections.

I am willing to use vaginal estrogen to prevent UTIs.

Exclusion Criteria

You cannot keep a vaginal tablet in place because of a severe prolapse or previous colpocleisis surgery.

I can't visit the clinic for follow-ups or to give samples due to transportation problems.

I am currently on hormone replacement therapy.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Phase 1

Participants receive either vaginal estradiol cream or tablet for 3 months

3 months

Monthly phone calls to assess side effects, safety concerns, and symptoms of UTI

Treatment Phase 2

Participants switch to the alternative treatment (cream or tablet) for another 3 months

3 months

Monthly phone calls to assess side effects, safety concerns, and symptoms of UTI

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Estradiol vaginal cream
• Estradiol Vaginal Tablet

Trial Overview The study compares the preference of women with recurrent urinary tract infections (rUTI) between two forms of vaginally applied estrogen: a cream and a tablet. It aims to determine which form increases compliance in using the treatment.

How Is the Trial Designed?

Group I: cream used first and then switch to tablets Active Control 2 Interventions

participants will start with 3 months of cream and then switch to tablets

Group II: tablets used first and switch to cream Active Control 2 Interventions

participants will start with 3 months of tablets and switch to cream

Who Is Running the Clinical Trial?

Wake Forest University Health Sciences

Lead Sponsor

Trials

1,432

Recruited

2,506,000+

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]

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 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]

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]

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]

Menopausal women experience significant urogenital changes due to reduced ovarian steroids, with estrogen therapy effectively alleviating symptoms like atrophic vaginitis and dryness, and reducing urinary tract infections.

Low-dose estrogen therapies, even in minimal amounts, can be absorbed systemically and help preserve bone density and improve lipid profiles, but should be combined with progestogen to mitigate the risk of endometrial cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vaginal hormone therapy for urogenital and menopausal symptoms. Ballagh, SA.[2005]

In a study of 414 postmenopausal women with type II diabetes, the use of 0.5 mg Estriol vaginal cream significantly reduced the prevalence of asymptomatic bacteriuria to 19.4% compared to 68.4% in the control group after 12 months (p < 0.001).

Estriol treatment also led to a decrease in symptomatic urinary tract infections (8.3% in the Estriol group vs. 18.4% in the control group, p < 0.001) and improved vaginal health indicators, while the control group showed no significant changes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Asymptomatic bacteriuria in postmenopausal women with diabetes mellitus. Kasyan, G., Berketova, TY., Rogozin, AK., et al.[2021]

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. auajournals.org auajournals.org/doi/10.1097/UPJ.0000000000000513

A Cost Savings Analysis of Topical Estrogen Therapy in ... For a patient with recurrent infections, topical estrogen therapy reported on average can reduce infections from 5 to 0.5 to 2 times per person ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3202002/

Guidelines for the diagnosis and management of recurrent ... Vaginal estrogen may be an effective prophylaxis measure for UTI in postmenopausal women. A 2007 Cochrane Database systematic review found two randomized ...

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S2405456922001262

Topical and Oral Oestrogen for Recurrent Urinary Tract ... Topical oestrogens are thought to have fewer systemic effects than their oral equivalents and have largely been shown to be safe for usage, despite the apparent ...

8. nejm.org nejm.org/doi/full/10.1056/NEJM199309093291102

A Controlled Trial of Intravaginal Estriol in Postmenopausal ... The intravaginal administration of estriol prevents recurrent urinary tract infections in postmenopausal women, probably by modifying the vaginal flora.