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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.
If a participant is part of the microbiome cohort, they will also be asked to do the following:
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| 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. |
|
| 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Estring Vaginal Product | Drug | estradiol vaginal ring, exchanged every 12 weeks |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| UTI rates | number of culture-proven urinary tract infections | the 6 month duration of the study |
| validated patient questionnaire - Urinary Distress Inventory Short Form (UDI-6) | Urinary Distress Inventory Short Form (UDI-6) - six questions, scored from 0 (not at all) to 3 (greatly), with higher scores indicating more distress from urinary symptoms. |
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Inclusion Criteria:
Exclusion Criteria:
Deferral criteria:
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| Name | Affiliation | Role |
|---|---|---|
| CHARLOTTE TER HAAR, MD | University of California, Irvine | Principal Investigator |
| Olivia Chang, MD | University of California, Irvine | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of California Irvine Medical Center | Orange | California | 92868 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 12113866 | Background | 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. | |
| 37178856 | 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. |
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| Vagifem | Drug | vaginal estrogen tablet, used twice per week |
|
| Estrace 0.01% Vaginal Cream | Drug | vaginal estrogen cream, used twice per week |
|
| 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) | UTI Symptoms Assessment Questionnaire (UTISA) - 15 questions, rated from 0 (did not have/not at all) to 3 (severe/a lot), with higher scores indicating a more symptomatic UTI | 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) | Treatment Satisfaction with Medications Questionnaire (SATMED-Q) - 17 questions, scored from 0 (not at all) to 4 (very much), with higher scores indicating greater satisfaction with medical treatment. | 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) | Patient Global Impression of Improvement Questionnaire (PGI-I) - one-question with scores from 1 (very much better) to 7 (very much worse0, with higher scores indicating a worsening in symptoms after treatment. | Questionnaires will be collected at the baseline visit, 3 month follow-up and 6 month follow-up |
| validated patient questionnaires - Medication Adherence Report Scale (MARS-5) | Medication Adherence Report Scale (MARS-5) - 5 questions, rated from 1 (always) to 5 (never), with a higher score indicating lower medication adherence. | Questionnaires will be collected at the baseline visit, 3 month follow-up and 6 month follow-up |
| optical coherence tomography measurements for nested OCT cohort - vaginal epithelial thickness | changes to vaginal epithelial thickness (VET) before and after treatment as measured by vaginal optical coherence tomography (OCT). | baseline and 6 month follow-up visits |
| optical coherence tomography measurements for nested OCT cohort - blood vessel density | changes to blood vessel density (BVD) before and after treatment as measured by vaginal optical coherence tomography (OCT). | baseline and 6 month follow-up visits |
| Vaginal health index for nested microbiome cohort | vaginal health index (VHI) before and after treatment - The Vaginal Health Index Score is a clinical tool that, by evaluating 5 parameters (vaginal elasticity, vaginal secretions, pH, epithelial mucous membrane, vaginal hydration), allows to obtain a final score defining the degree of atrophy in the genitourinary tract by assigning a single score to each parameter. Total score ranges from 5 to 25, with lower scores corresponding to greater urogenital atrophy | baseline and 6 month follow-up visits |
| Vaginal maturation index for nested microbiome cohort | vaginal maturation index (VMI) before and after treatment - microscopic evaluation of the ratio of vaginal epithelial cells (parabasal, intermediate and superficial) | baseline and 6 month follow-up visits |
| Urologic microbiome results for nested microbiome cohort | Urologic microbiome before and after treatment (Lactobacillus abundance processed by Zymo analysis). | baseline and 6 month follow-up visits |
| Vaginal microbiome results for nested microbiome cohort | Vaginal microbiome before and after treatment (Lactobacillus abundance processed by Zymo analysis). | baseline and 6 month follow-up visits |
| 18757671 | 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. |
| 29369839 | 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. |
| 8350884 | 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. |
| 10329858 | 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. |
| 25944522 | 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. |
| 23526171 | 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. |
| 27648663 | 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. |
| 10810960 | 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. |
| ID | Term |
|---|---|
| D014552 | Urinary Tract Infections |
| ID | Term |
|---|---|
| D007239 | Infections |
| D014570 | Urologic Diseases |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D052801 | Male Urogenital Diseases |
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| ID | Term |
|---|---|
| D004958 | Estradiol |
| D014622 | Vaginal Creams, Foams, and Jellies |
| ID | Term |
|---|---|
| D004963 | Estrenes |
| D004962 | Estranes |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
| D045166 | Estradiol Congeners |
| D012739 | Gonadal Steroid Hormones |
| D042341 | Gonadal Hormones |
| D006728 | Hormones |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |
| D004304 | Dosage Forms |
| D004364 | Pharmaceutical Preparations |
| D053566 | Feminine Hygiene Products |
| D004864 | Equipment and Supplies |
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