Vaginal Testosterone for Recurrent Urinary Tract Infections

(PIVoT Trial)

Overseen By Alison Polland, MD

Age: 18+

Sex: Female

Trial Phase: Phase 4

Sponsor: Maimonides Medical Center

Must not be taking: Antibiotics, Vaginal estrogen

Disqualifiers: Current UTI, STI, Urinary retention, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

Duration: 9 months

100 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether a vaginal testosterone cream can reduce urinary tract infections (UTIs) in postmenopausal women. Researchers aim to determine if this cream is more effective than a placebo (a harmless substance with no therapeutic effect) in lowering UTI rates and improving vaginal health. Postmenopausal women who have experienced frequent UTIs are ideal candidates, particularly if they cannot or prefer not to use estrogen creams. Participants will use either the testosterone cream or a placebo cream for nine months. As a Phase 4 trial, this study involves an FDA-approved treatment and seeks to understand its benefits for a broader patient population.

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've used antibiotics or vaginal probiotics in the last 4 weeks. If you're on oral estrogen therapy, you can still join the study.

What is the safety track record for Vaginal Testosterone Cream?

Research has shown that vaginal testosterone cream may benefit postmenopausal women, particularly those undergoing certain breast cancer treatments. It can alleviate issues such as vaginal dryness and discomfort. While its effect on urinary tract infections (UTIs) remains under investigation, testosterone creams are generally well-tolerated. Past studies have not identified major side effects from their use, suggesting that vaginal testosterone cream could be a safe option for many women. However, individual reactions can vary, so discussing any concerns with a healthcare provider is important. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Unlike the standard antibiotics typically used to prevent recurrent urinary tract infections (UTIs), vaginal testosterone cream offers a novel approach by potentially strengthening the vaginal mucosa and restoring healthy flora. This treatment is unique because it harnesses the hormone testosterone in a topical form, targeting local tissues directly rather than systemically. Researchers are excited about this treatment because it could reduce the frequency of UTIs without contributing to antibiotic resistance, a growing concern with current standard treatments.

What evidence suggests that vaginal testosterone cream might be an effective treatment for recurrent urinary tract infections?

Research has shown that vaginal testosterone cream might help balance vaginal pH and ease symptoms like dryness and pain during sex. Early results suggest it could also address menopause-related issues, possibly lowering the risk of urinary tract infections (UTIs). Although the specific effects on UTIs are not fully understood, the cream seems to improve overall vaginal health. In this trial, researchers are testing the vaginal testosterone cream against a placebo to determine its effectiveness in reducing UTIs in postmenopausal women. ^{1 2 6 7 8}

Are You a Good Fit for This Trial?

This trial is for postmenopausal women aged 60-90 with recurrent UTIs, who are not using vaginal estrogen but may be on oral estrogen or have a history of breast/endometrial cancer and taking aromatase inhibitors. Women with prior vaginal surgeries can join, but those with current UTI, recent antibiotic/probiotic use, large post-void residual volume, untreated hematuria or chronic catheter/stent use cannot participate.

Inclusion Criteria

I am currently taking oral estrogen therapy.

I cannot or do not want to use topical estrogen.

I have had 3 or more UTIs in the last year.

Exclusion Criteria

You have unexplained blood in your urine.

I am able to follow the study's requirements and attend all follow-ups.

You currently have a sexually transmitted infection.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either vaginal testosterone cream or placebo cream, applied once each night for two weeks followed by twice-weekly applications for a total duration of nine months

9 months

Initial visit, 4.5 months visit, 9 months visit

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of vaginal flora, pH, and UTI symptoms

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Vaginal Testosterone Cream

Trial Overview The study tests if applying vaginal testosterone cream reduces urinary tract infections in postmenopausal women more effectively than a placebo. It also examines the impact on vaginal pH and flora. Participants will receive either the testosterone cream or placebo through an applicator to apply themselves.

How Is the Trial Designed?

Group I: Vaginal Testosterone Cream Arm Experimental Treatment 1 Intervention

Women enrolled in this arm will receive vaginal testosterone cream to be applied once each night for two weeks followed by twice-weekly applications for a total duration of nine months.

Group II: Vaginal Placebo Cream Arm Placebo Group 1 Intervention

Women enrolled in this arm will receive vaginal placebo cream to be applied once each night for two weeks followed by twice-weekly applications for a total duration of nine months.

Vaginal Testosterone Cream is already approved in United States, European Union for the following indications:

Approved in United States as Vaginal Testosterone Cream for:

• Hypoactive Sexual Desire Disorder (HSDD) in premenopausal women
• Not specifically approved for UTI prevention

Approved in European Union as Vaginal Testosterone Cream for:

• Not specifically approved for UTI prevention

Who Is Running the Clinical Trial?

Maimonides Medical Center

Lead Sponsor

Trials

72

Recruited

15,400+

American Urological Association

Collaborator

Trials

5

Recruited

640+

Published Research Related to This Trial

A systematic review of 11 studies, including 6 randomized control trials with 2,236 participants and 5 observational studies with over 1.2 million participants, found no significant association between testosterone therapy and the risk of venous thromboembolism (VTE).

Despite concerns about the safety of testosterone therapy, the evidence currently available does not support an increased risk of VTE, although the overall certainty of the evidence is low.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Testosterone therapy and venous thromboembolism: A systematic review and meta-analysis. Houghton, DE., Alsawas, M., Barrioneuvo, P., 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]

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 60 healthy adult males, scrotal testosterone transdermal systems caused significantly less topical irritation compared to nonscrotal systems, with only 5% of scrotal users reporting moderate irritation versus 32% for nonscrotal users.

No confirmed cases of allergic contact dermatitis were observed with the scrotal system, while 12% of subjects using nonscrotal systems experienced allergic reactions, indicating that the scrotal system may be a safer option for testosterone delivery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Allergy and topical irritation associated with transdermal testosterone administration: a comparison of scrotal and nonscrotal transdermal systems. Jordan, WP.[2013]

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 systematic review of 13 randomized controlled trials involving 5050 men, testosterone replacement therapy (TRT) did not show an increased risk of venous thromboembolism (VTE) compared to placebo, with a relative risk of 1.03 (95% CI: 0.49-2.14).

Despite the findings suggesting no significant association between TRT and VTE, the wide confidence intervals indicate that a clinically important increased risk cannot be completely ruled out, highlighting the need for further research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Testosterone replacement therapy and the risk of venous thromboembolism: A systematic review and meta-analysis of randomized controlled trials. Ayele, HT., Brunetti, VC., Renoux, C., et al.[2021]

Testosterone replacement therapy (TRT) does not appear to significantly increase the risk of disease progression in men with prostate cancer compared to those not receiving TRT, based on a systematic review of 36 studies involving 2,459 patients.

However, TRT may be harmful for men with advanced prostate cancer, those undergoing active surveillance, and those with high-risk disease after treatment, indicating that caution is needed in these populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Testosterone Replacement Therapy in Men with Untreated or Treated Prostate Cancer: Do We Have Enough Evidences? Kim, M., Byun, SS., Hong, SK.[2021]

Vaginal estrogen therapy has been shown to improve symptoms of overactive bladder (OAB) in postmenopausal women, although its effectiveness may vary when combined with other treatments.

Vaginal hormone therapy, including estrogen and prasterone (DHEA), is effective for treating recurrent urinary tract infections (UTIs) but has inconclusive results for stress urinary incontinence (SUI) and interstitial cystitis/bladder pain syndrome (ICS/BPS).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vaginal Hormone Therapy for Conditions of the Lower Urinary Tract. Nemirovsky, A., Villela, NA., Yuan, JC., 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]

Testosterone replacement therapy (TRT) shows promise for treating hypogonadism in older men, but significant safety concerns remain unresolved due to a lack of large-scale randomized trials comparing untreated hypogonadism with long-term TRT use.

Meta-analyses have identified key adverse events associated with TRT, including polycythemia, increased prostate-related events, and a slight reduction in HDL cholesterol, but the overall safety and utility of TRT continue to be debated in the medical community.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Review of health risks of low testosterone and testosterone administration. Jia, H., Sullivan, CT., McCoy, SC., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04807894

Prevention of Recurrent UTI Using Vaginal Testosterone ... It is anticipated that vaginal testosterone cream will reduce the incidence of urinary tract infections in postmenopausal women when compared to placebo. It is ...

2. academic.oup.com academic.oup.com/jsm/article/20/Supplement_1/qdad060.002/7164753

(002) The Effects of Vaginal Testosterone versus Placebo on ... Initial data demonstrates improvement in vaginal pH and VHI after 9 months of treatment with VT. Improvement in sexual function scores were also ...

3. trialfinder.panfoundation.org trialfinder.panfoundation.org/en-US/trial/listing/538775

Prevention of Recurrent UTI Using Vaginal Testosterone ... Outcome measures. Primary outcome measures. To assess whether topical vaginal testosterone cream is more effective than placebo in reducing ...

4. auajournals.org auajournals.org/doi/10.1097/JU.0000000000003251.08

PD11-08 THE EFFECT OF VAGINAL TESTOSTERONE ON ... CONCLUSIONS: Interim analysis showed greater long term improvement in VHI scores with VT as compared to placebo, while FSFI improved in both ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8058921/

Update in Female Hormonal Therapy: What the Urologist ... Recurrent UTIs are very common in postmenopausal women. The use of vaginal estrogen therapy is both safe and efficacious in lowering UTI risk. Vaginal estrogen ...

6. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK557479/

Recurrent Urinary Tract Infections - StatPearls - NCBI Bookshelf Estrogen vaginal cream: The topical treatment reduces recurrent UTIs in ... recurrent UTIs in several studies with safety data and minimal adverse effects.

7. ctv.veeva.com ctv.veeva.com/study/preference-of-women-with-recurrent-urinary-tract-infection-for-vaginal-estradiol-tablet-vs-cream

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

8. solace.health solace.health/articles/utis-after-menopause-a-preventable-crisis-for-women

UTIs After Menopause: A Preventable Crisis For Women Vaginal estrogen therapy cuts UTI risk by more than 50% and is remarkably safe. Applied directly where needed as a cream, tablet, or ring, this ...