Adherence to Vaginal Estrogen Therapy in Hypoestrogenic Women With Recurrent Urinary Tract Infections

NCT06353269 | Active Not Recruiting Phase 4 DMC FDA Drug

• 1 other identifier: 4255
• Study Type: interventional
• Target: 111
• Locations: 1 country
• Sites: 1

Brief Summary

• The goal of this clinical trial is to learn about medication adherence to difference types of vaginal estrogen in women with low levels of estrogen (for example, post-menopausal women) who have recurrent urinary tract infections. Medication adherence means whether patients take their medicine as prescribed.
• Another goal of the study is to learn about changes to the skin of the vagina before and after estrogen treatment, using a specialized imaging modality called optical coherence tomography, which is similar to receiving an ultrasound.
• A third goal of the study is to learn about changes to the microbiome (all the bacteria that naturally live in our bodies) before and after treatment with vaginal estrogen. The researchers will be looking specifically at the microbiome in the urine and the vagina. Participants will be assigned by chance (like the flip of a coin) to receive one of three possible vaginal estrogen treatments - cream, tablets, or drug-eluting ring.
• The main study tests and procedures include an initial visit in which the researchers will collect baseline information about participants and have participants complete a series of questionnaires.
• There will then be 3 and 6 month follow-ups in which the researchers will have participants complete additional questionnaires and the researchers also assess whether participants are using the vaginal estrogen treatment that you were prescribed. If a participant is part of the microbiome cohort, they will also be asked to do the following:
• a baseline visit in which urinary and vaginal specimens are collected to assess their baseline microbiome. The vaginal specimen collection will involve a q-tip swab inside the vagina; it is similar to a pap smear.
• Finally, participants will have an imaging modality performed on their vagina called optical coherence tomography, which allows the researchers to assess the thickness of the vaginal walls and the blood vessel density. This imaging modality involves the insertion of a thin probe into the vagina to obtain the images of the vaginal wall.
• These tests will then be repeated at 6 months to assess if vaginal estrogen treatment causes changes to the vagina.

Conditions

Hypoestrogenism; Recurrent Urinary Tract Infection

Keywords

vaginal estrogen

Outcome Measures

Primary Outcomes (1)

• Adherence to vaginal estrogen treatment

  The primary outcome will be the adherence to vaginal estrogen treatment at the 6 month follow-up visit. The 6 month follow-up visit will be the endpoint of the study. The investigators will consider both subjective, patient-reported adherence at 6 months, as well as objective data - tube weight for the estrogen cream, number of tablets left for the estrogen tables, and presence or absence of drug-eluting ring on physical exam for the estrogen ring.

  6 month follow-up visit

Secondary Outcomes (12)

• UTI rates

  the 6 month duration of the study

• validated patient questionnaire - Urinary Distress Inventory Short Form (UDI-6)

  Questionnaires will be collected at the baseline visit, 3 month follow-up and 6 month follow-up

• validated patient questionnaires - UTI Symptoms Assessment Questionnaire (UTISA)

  Questionnaires will be collected at the baseline visit, 3 month follow-up and 6 month follow-up

• validated patient questionnaires - Treatment Satisfaction with Medications Questionnaire (SATMED-Q)

  Questionnaires will be collected at the baseline visit, 3 month follow-up and 6 month follow-up

• validated patient questionnaires - Patient Global Impression of Improvement Questionnaire (PGI-I)

  Questionnaires will be collected at the baseline visit, 3 month follow-up and 6 month follow-up

Study Arms (3)

Estrogen cream

EXPERIMENTAL

Participants in this arm will receive the vaginal estrogen cream (Estrace 0.01%) for treatment. Participants will apply 0.5gm twice per week for the duration of the study.

Drug: Estrace 0.01% Vaginal Cream

Estrogen tablet

EXPERIMENTAL

Participants in this arm will receive the vaginal estrogen tablets (Vagifem) for treatment. Participants will place one tablet (10 mcg) into the vagina twice per week for the duration of the study.

Drug: Vagifem

Estrogen drug-eluting ring

EXPERIMENTAL

Participants in this arm will receive the vaginal estrogen drug-eluting ring (Estring) for treatment. Participants will have the ring placed by a provider at their clinical visit. The ring will be exchanged every 12 weeks.

Drug: Estring Vaginal Product

Interventions

Estring Vaginal Product DRUG

estradiol vaginal ring, exchanged every 12 weeks

Estrogen drug-eluting ring

Vagifem DRUG

vaginal estrogen tablet, used twice per week

Estrogen tablet

Estrace 0.01% Vaginal Cream DRUG

vaginal estrogen cream, used twice per week

Estrogen cream

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• female, at least 18 years old with diagnosis of hypoestrogenism (defined by post-menopausal status of 12 months or more of amenorrhea, history of bilateral salpingo-oophorectomy) AND recurrent UTI as defined by greater than or equal to 3 in 1 year or 2 in 6 months by positive urine culture or clinically suspected UTI)

You may not qualify if:

• Have a known etiology of infections (urologic stones, fistulas, fecal incontinence, catheterization, or poorly controlled diabetes - Hgb A1C cutoff of 8)
• Contraindication to vaginal estrogen (actively treated estrogen-sensitive tumor, allergies to medication formulation, inability to apply or place vaginal estrogen of any modality)
• Suspected mesh complications or voiding problems from pelvic reconstructive surgery
• Short vaginal length (less than 7cm) or poor dexterity or mobility that may prevent use of estrogen ring
• Do not speak English
• For the nested cohort only - patients currently using vaginal estrogen greater than 2x per month
• Deferral criteria:
• Undiagnosed hematuria or vaginal bleeding; however enrollment may proceed after negative workup for malignancy
• Remote history of estrogen-sensitive tumor: enrollment allowed after approval by oncologist or primary care physician

Sponsors & Collaborators

• University of California, Irvine: lead

Study Sites (1)

University of California Irvine Medical Center

Orange, California, 92868, United States

Location

Related Publications (10)

• Foxman B. Epidemiology of urinary tract infections: incidence, morbidity, and economic costs. Am J Med. 2002 Jul 8;113 Suppl 1A:5S-13S. doi: 10.1016/s0002-9343(02)01054-9.

  PMID: 12113866 BACKGROUND

• Tan-Kim J, Shah NM, Do D, Menefee SA. Efficacy of vaginal estrogen for recurrent urinary tract infection prevention in hypoestrogenic women. Am J Obstet Gynecol. 2023 Aug;229(2):143.e1-143.e9. doi: 10.1016/j.ajog.2023.05.002. Epub 2023 May 11.

  PMID: 37178856 BACKGROUND

• Perrotta C, Aznar M, Mejia R, Albert X, Ng CW. Oestrogens for preventing recurrent urinary tract infection in postmenopausal women. Obstet Gynecol. 2008 Sep;112(3):689-90. doi: 10.1097/AOG.0b013e318185f7a5. No abstract available.

  PMID: 18757671 BACKGROUND

• Brubaker L, Carberry C, Nardos R, Carter-Brooks C, Lowder JL. American Urogynecologic Society Best-Practice Statement: Recurrent Urinary Tract Infection in Adult Women. Female Pelvic Med Reconstr Surg. 2018 Sep/Oct;24(5):321-335. doi: 10.1097/SPV.0000000000000550. No abstract available.

  PMID: 29369839 BACKGROUND

• Raz R, Stamm WE. A controlled trial of intravaginal estriol in postmenopausal women with recurrent urinary tract infections. N Engl J Med. 1993 Sep 9;329(11):753-6. doi: 10.1056/NEJM199309093291102.

  PMID: 8350884 BACKGROUND

• Eriksen B. A randomized, open, parallel-group study on the preventive effect of an estradiol-releasing vaginal ring (Estring) on recurrent urinary tract infections in postmenopausal women. Am J Obstet Gynecol. 1999 May;180(5):1072-9. doi: 10.1016/s0002-9378(99)70597-1.

  PMID: 10329858 BACKGROUND

• Portman D, Shulman L, Yeaw J, Zeng S, Uzoigwe C, Maamari R, Iyer NN. One-year treatment persistence with local estrogen therapy in postmenopausal women diagnosed as having vaginal atrophy. Menopause. 2015 Nov;22(11):1197-203. doi: 10.1097/GME.0000000000000465.

  PMID: 25944522 BACKGROUND

• Minkin MJ, Maamari R, Reiter S. Improved compliance and patient satisfaction with estradiol vaginal tablets in postmenopausal women previously treated with another local estrogen therapy. Int J Womens Health. 2013;5:133-9. doi: 10.2147/IJWH.S41897. Epub 2013 Mar 15.

  PMID: 23526171 BACKGROUND

• Weissmann-Brenner A, Bayevsky T, Yoles I. Compliance to vaginal treatment-tablets versus cream: a retrospective 9 years study. Menopause. 2017 Jan;24(1):73-76. doi: 10.1097/GME.0000000000000729.

  PMID: 27648663 BACKGROUND

• Rioux JE, Devlin C, Gelfand MM, Steinberg WM, Hepburn DS. 17beta-estradiol vaginal tablet versus conjugated equine estrogen vaginal cream to relieve menopausal atrophic vaginitis. Menopause. 2000 May-Jun;7(3):156-61. doi: 10.1097/00042192-200007030-00005.

  PMID: 10810960 BACKGROUND

MeSH Terms

Conditions

Urinary Tract Infections

Interventions

Estradiol; Vaginal Creams, Foams, and Jellies

Condition Hierarchy (Ancestors)

Infections; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Dosage Forms; Pharmaceutical Preparations; Feminine Hygiene Products; Equipment and Supplies

Study Officials

• CHARLOTTE TER HAAR, MD

  University of California, Irvine

  PRINCIPAL INVESTIGATOR

• Olivia Chang, MD

  University of California, Irvine

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: HEALTH SERVICES RESEARCH
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Resident Physician

Study Record Dates

• First Submitted: February 28, 2024
• First Posted: April 9, 2024
• Study Start: June 14, 2024
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): September 1, 2027
• Last Updated: January 22, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)