Vaginal Estradiol Treatments for Recurrent Urinary Tract Infections

Overseen by Candace Parker-Autry, MD

Age: 18+

Sex: Female

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 4

Recruiting

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

Prior Safety Data

Trial Summary

What is the purpose of this trial?

Vaginally applied estrogen has been shown to decrease the incidence of Recurrent Urinary Tract Infection (rUTI) in post-menopausal women. However, prior studies have shown the compliance rate for topical estrogen cream is low. The vaginal estradiol tablet has been shown to be preferred by patients being treated for genitourinary syndrome of menopause and has improved compliance. There are no studies looking at the preference of post-menopausal women with rUTI for vaginal estradiol tablet as an alternative to vaginal estradiol cream.

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 data supports the effectiveness of the treatment Estradiol vaginal cream and Estradiol Vaginal Tablet for recurrent urinary tract infections?

Research suggests that vaginal estrogen, like the Estradiol cream and tablet, can help prevent recurrent urinary tract infections in postmenopausal women by improving the health of the vaginal and urinary tract tissues. ^{1 2 3 4 5}

Is vaginal estradiol treatment safe for humans?

Vaginal estradiol treatments, like creams and tablets, are generally considered safe for humans, especially for postmenopausal women. They are used to treat symptoms like dryness and urinary tract infections, with studies showing they have a low risk of serious side effects when used at low doses. ^{1 2 3 6 7}

How does the drug Estradiol vaginal cream or tablet differ from other treatments for recurrent urinary tract infections?

Estradiol vaginal cream and tablets are unique because they deliver estrogen directly to the vaginal area, which helps restore the natural balance and reduce the risk of urinary tract infections in postmenopausal women. This local application is different from systemic estrogen treatments, which affect the whole body and are not recommended for this condition. ^{1 2 3 5 8}

Research Team

Candace Parker-Autry, MD

Principal Investigator

Wake Forest University Health Sciences

Eligibility Criteria

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 have not used vaginal estrogen in the last month.

Trial Timeline

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

Treatment Details

Interventions

• Estradiol vaginal cream (Estrogen)
• Estradiol Vaginal Tablet (Estrogen)

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.

Participant Groups

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+

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]

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]

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]

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]

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]

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

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

4. Poland pubmed.ncbi.nlm.nih.gov

Asymptomatic bacteriuria in postmenopausal women with diabetes mellitus. [2021]

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

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

6. 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]

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

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

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

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