Lower Urinary Tract SymptomsPhase 4NCT06508944
Efficacy of Vaginal 17β-Estradiol on the Urinary Storage Symptoms in Postmenopausal Women
A Phase 4 study testing vaginal 17 beta-estradiol and Behavioral modifications in people with Lower Urinary Tract Symptoms and Female Genitourinary Disease, run by Mahidol University at 1 site in Thailand.
Trial summary
The goal of this clinical trial is to evaluate whether vaginal 17β-estradiol effectively treats storage symptoms of lower urinary tract symptoms (LUTS) and enhances quality of life. Read more about this study
- Who is it for?
- Any age, women only
- Conditions the study is for
- Lower Urinary Tract Symptoms, Female Genitourinary Disease, Urinary Stress Incontinence
- What is being tested?
- vaginal 17 beta-estradiol and Behavioral modifications
- Type of treatment
- Pill or oral medicine, Lifestyle or therapy programme
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 86 participants
- Where
- 1 siteThailand
- Study dates
- 8 Apr 2024to 31 Oct 2024
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- Women only
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Presenting with storage phase symptom score more than/equal to 1 evaluated by the ICIQ-FLUTS questionnaire in these items
- Item 2a) nocturia and/or
- Item 3a) urgency and/or
- Item 5a) daytime frequency and/or
- Item 9a) UUI and/or
- Item 11a) SUI
Show all 11Show fewer
- Being natural or surgical menopause for more than 1 year
- Absence of urinary tract infection or other identifiable cause
- Not using hormone replacement therapy or any route of estrogen within 4 weeks
- Never undergone onabotulinumtoxinA therapy, percutaneous tibial nerve stimulation (PTNS), or neuromodulation for overactive bladder (OAB) treatment
- Willing to adhere to the research protocol and actively participate in the scheduled follow-up appointments as delineated within the framework of this study
Who cannot join
- Contraindication for estrogen therapy: undiagnosed abnormal vaginal bleeding, previous thromboembolic event, breast cancer, gynecologic/genitourinary malignancy, active liver disease
- Pelvic organ prolapse of anterior compartment stage III and IV
- Immunocompromised patient or taking immunosuppressant drug
- History of antibiotics drug use within the past 7 days
- History of bladder outlet obstruction
- History of using anti-muscarinics, beta3-adrenoceptor agonists, vaginal energy-based devices (laser and radiofrequency) or electromagnetic energy-based therapies within the past 2 weeks
Show all 9Show fewer
- History of documented positive urine culture in the past 6 weeks
- Have an allergic reaction to study's drug
- Any other significant finding that in the opinion of the investigator would increase the risk of having an adverse outcome from participating in this study
Trial locations and contacts
1 site in 1 country.
Thailand1 site
Faculty of Medicine Ramathibodi Hospital, Mahidol University
Ratchathewi, Bangkok, 10400
About this study
Official title: Efficacy of Vaginal 17β-Estradiol on the Urinary Storage Symptoms in Postmenopausal Women: A Randomized Double-Blind, Placebo-Controlled Study
The goal of this clinical trial is to evaluate whether vaginal 17β-estradiol effectively treats storage symptoms of lower urinary tract symptoms (LUTS) and enhances quality of life. The main questions it aims to answer are:
- What is the efficacy of vaginal 17β-estradiol treatment compared to placebo in alleviating storage symptoms of LUTS?
- How does vaginal 17β-estradiol treatment affect the urethral maturation index and vaginal pH compared to placebo?
- What impact does vaginal 17β-estradiol treatment have on overall quality of life and patients' perception of global improvement (PGI)?
Read more
Participants in the trial will undergo the following procedures:
- Screening procedures at the first visit to exclude correctable causes of LUTS and to complete a bladder diary.
- Visit the clinic at 1-2 weeks for a review of the bladder diary and a check-up. Participants will receive the assigned dosage of vaginal 17β-estradiol or placebo: one vaginal tablet daily for two weeks, followed by one vaginal tablet twice a week for 10 weeks.
- The third and fourth visits (at 4 and 12 weeks after treatment) will involve: completion of bladder diaries, questionnaires, vaginal pH testing, collection of urethral maturation index (UMI), observation of intervention's side effects and monitoring of LUTS symptoms.
Read the detailed description
- First Visit and Recruitment
Participants will be recruited from the urogynecology clinic, menopause clinic, and urology clinic using hospital and public advertisement. An information sheet in Thai language will be provided to health care providers in the designated outpatient department (OPD) which can ensure the providers convey the correct study information to potential participant. Participants will only be able to enroll into this study one time.
Informed Consent
Individuals with at least one storage symptom of LUTS presenting to clinics in selected OPD will undergo the informed consent process by principal investigator prior to initiating screening procedures. Consent form in Thai language describing in detail the study procedures will be given to the participant privately in a separate room, and extensive discussion of risks and possible benefits of participation in this study will be provided. Participation will be informed that they may withdraw consent at any time throughout the course of this study.
Screening
After documentation of informed consent, principal investigator will interview the participant and perform vital signs and physical examination. The urinalysis will be performed by urinalysis test strip before the start of the study. Screening procedures are as follows;
- Pelvic exam
- Pelvic floor muscle strength measured as Brink scale
- Pelvic Organ Prolapse Quantification (POP-Q), Stress test
- Gynecologic ultrasonography with post-void residual volumes (PVR)
- Urinalysis by urinalysis test strip
- Bladder diary: consecutive three-day diary which the time of each micturition and the volume voided, fluid intake, incontinence episodes, episodes of urgency and sensation will be recorded, as might be the activities performed during or immediately preceding the involuntary loss of urine.
After screening procedure, the appointment will be made for the next visit, which is one or two weeks after first visit.
Bladder diary
The study will incorporate the use of essential diagnostic tool, namely the bladder diary, to assess and monitor the outcomes. These assessments will be administered under the careful supervision of the study investigators. These diagnostic tests play a pivotal role in our research, serving as indispensable instruments for evaluating the progression and ultimate success of the treatment interventions.
II. Second Visit and Randomization
At one or two weeks after 1st visit, the following study procedure will be performed;
- Bladder diary interpretation
- ICIQ-FLUTS questionnaire
- ICIQ-LUTSqol questionnaire
- Vaginal pH
- Urethral maturation index (UMI)
After evaluating all the data collected during the screening process at the initial visit and combining it with the procedures conducted during the second visit, if the woman does not meet all study inclusion or if the woman has an exclusion criterion, she will not be enrolled into this study. A screening log will be kept of all who were evaluated for participation to document who is and is not enrolled and reason for not enrolling in this study.
Women who meet inclusion criteria will be randomized with block randomization technique and a ratio of treatments of 1:1. The sequence generation will be performed under supervision of a senior statistician at the section of Clinical Epidemiology and Biostatistics in Ramathibodi Hospital. The random sequences will be generated using Stata version 18. This is an automated process with no interfere from the investigators. Upon a subject's successful enrollment in the clinical trial following eligibility assessment, principal investigator or research personnel shall provide participants with a comprehensive Thai guidebook for behavior modification which is designed to ensure the harmonization of knowledge and behaviors among all trial participants. This guidebook was developed and published by The International Urogynecological Association (IUGA) and will be distributed by research assistants.
Trial Treatment: Dosage Form, Regimen, Route of Administration
- 17beta-Estradiol 10 mcg (Femiest® Pharma Munster GMBH, Muenster, Germany (ESTRADIOL HEMIHYDRATE 0.0103 milligram, pH 6.94) 17beta-Estradiol will be administered to group A treatment arm intravaginally. The assigned dosage will be one vaginal tablet daily for two weeks then one vaginal tablet twice a week for 10 weeks. Participants will be carefully monitored for any changes in clinical condition in each follow-up visits using logbook. It is important to clarify that the investigators are not using 17beta-Estradiol (Vagifem®) 25 mcg as the study drug. Although 17beta-Estradiol 25 mcg is frequently mentioned in literature reviews and has been historically used for treating vaginal dryness, this drug is currently not available in Thailand. Therefore, the investigators are using 17beta-Estradiol (Femiest®) 10 mcg as an alternative for our study drug. Notably, 17beta-Estradiol 10 mcg has been shown to provide a therapeutic dose equivalent to that of 17beta-Estradiol 25 mcg for treatment, as stated by the FDA. This decision ensures that participants receive an effective and appropriate dosage while adhering to the availability of medications in our region.
- Placebo
Placebo will be administered to group B treatment arms intravaginally. The assigned dosage will be one vaginal tablet daily for two weeks then one vaginal tablet twice a week for 10 weeks. Participants will be carefully monitored for any changes in clinical condition in each follow-up visits. Placebo is produced by Chulalongkorn University Drug and Health Products Innovation \& Promotion Center, Faculty of Pharmaceutical Sciences, Chulalongkorn University. Details for presentation and packing are as follows;
- Appearance: White, round, biconvex with "E" imprint one side
- Weight: 106 - 110 mg
- Hardness: 4.1 - 4.8 kilopond (kp)
- Thickness: 3.26 - 3.3 mm
- Diameter: 6.02 - 6.03 mm
- Disintegration time: 4 min 58sec - 7min 42sec
- pH: 7.18
Placebo contains
- Agglomerated Lactose
- Microcrystalline cellulose PH 102
- Magnesium stearate
Both subject groups will be counseled on potential signs/symptoms of adverse events and post-marketing experience, such as breast pain, peripheral edema, and postmenopausal bleedings. Due to the vaginal administration and minimal systemic absorption, it is unlikely that any clinically relevant drug interactions will occur with 17beta-Estradiol. However, interactions with other locally applied vaginal treatments will be considered and advised to the patients. If a dose is forgotten, participants will be advised that it should be taken as soon as he/she remembers. A double dose should be avoided.
Random allocation
Each participant in the study will receive a prescription for the research drug, an adequate supply to cover a 12-week treatment duration. This drug will be uniformly packaged within identical containers, featuring a unique alphanumeric code and detailed usage instructions on the label, thereby avoiding the inclusion of the original medication name. The data analysis will be performed by a statistician who will be the sole individual privy to the allocation of drug A or drug B to their respective groups. It is essential to note that the statistician will remain unaware of which of the two is the active drug and which is the placebo. Additionally, an independent statistician will maintain a sealed randomization list as a contingency. Allocation will be as follows;
Group A: 17beta-Estradiol 10 mcg (Femiest® Haupt Pharma Munster GMBH, Muenster, Germany (ESTRADIOL HEMIHYDRATE 0.0103 milligram)
Group B: Placebo
III. Third Visit
At four weeks after 2nd visit, the following study procedure will be performed;
- Bladder diary, the participant will be reminded to provide a three-day diary prior to schedule visit date.
- ICIQ-FLUTS questionnaire
- ICIQ-LUTSqol questionnaire
- PGI-I score
- Vaginal pH
- Urethral maturation index (UMI)
Participants will also have clinical evaluation and vital signs measurements evaluated. Compensation for participants will be provided.
IV. Fourth and Final Visit
At eight weeks after 3rd visit, the following study procedure will be performed;
- Pelvic exam
- Pelvic floor muscle strength measured as Brink scale
- Bladder diary, the participant will be reminded to provide a three-day diary prior to schedule visit date.
- ICIQ-FLUTS questionnaire
- ICIQ-LUTSqol questionnaire
- PGI-I score
- Vaginal pH
- Urethral maturation index (UMI)
Participants will also have clinical evaluation and vital signs measurements evaluated. Compensation for participants will be provided.
- Conditions
- Lower Urinary Tract Symptoms, Female Genitourinary Disease, Urinary Stress Incontinence, Urinary Urge Incontinence, Nocturia, Quality of Life
- Being tested
- vaginal 17 beta-estradiol, Placebo, Behavioral modifications
- Keywords
- 17 beta-estradiol, lower urinary tract symptoms, postmenopause, female genitourinary diseases, urethral maturation index, vaginal pH, ICIQ-FLUTS, ICIQ-LUTSqol, PGI-I, randomized controlled trial, vaginal estrogen, urinary stress incontinence, urinary urge incontinence, nocturia, quality of Life, voiding Disorders, vagina Atrophy, urethral Atrophy, daytime frequency, urgency
- Medical subject headings
- Lower Urinary Tract Symptoms, Female Urogenital Diseases, Urinary Incontinence, Stress, Urinary Incontinence, Urge, Nocturia, Urinary Bladder, Overactive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
vaginal 17 beta-estradiolDrug
Also called Femiest, ESTRADIOL HEMIHYDRATE, vagifem
- Femiest® Haupt Pharma Munster GMBH, Muenster, Germany
- The assigned dosage will be one vaginal tablet daily for two weeks then one vaginal tablet twice a week for 10 weeks.
PlaceboDrug
Also called Agglomerated Lactose, Microcrystalline cellulose PH 102, Magnesium stearate
- Placebo is produced by Chulalongkorn University Drug and Health Products Innovation \& Promotion Center.
- The assigned dosage will be one vaginal tablet daily for two weeks then one vaginal tablet twice a week for 10 weeks.
Behavioral modificationsBehavioural
Behavioral modifications for women with storage symptoms of lower urinary tract symptoms (LUTS) involve strategies such as regulating fluid intake, avoiding bladder irritants, practicing bladder training techniques (scheduled and delayed voiding), performing pelvic floor muscle exercises, managing weight, increasing dietary fiber, maintaining a bladder diary, setting a regular voiding schedule, utilizing stress management techniques, and educating patients about LUTS.
| Study group | Role | What they receive |
|---|---|---|
| Group A: Behavioral modifications and vaginal 17beta-estradiol | Experimental | • 17beta-Estradiol 10 mcg + Behavioral modifications Receives: Drug: vaginal 17 beta-estradiol; Behavioral: Behavioral modifications |
| Group B: Behavioral modifications + Placebo | Placebo comparator | • Placebo + Behavioral modifications Receives: Drug: Placebo; Behavioral: Behavioral modifications |
What is being measured
The primary outcome is the main question the study is designed to answer.
Storage symptom improvement
Storage Symptom Improvement: This will be evaluated using the International Consultation on Incontinence Questionnaire-Female Lower Urinary Tract Symptoms (ICIQ-FLUTS), validated in Thai. The questionnaire includes 5 items addressing storage symptoms:
- 2a) Nocturia
- 3a) Urgency
- 5a) Daytime frequency
- 9a) Urgency urinary incontinence (UUI)
- 11a) Stress urinary incontinence (SUI)
Each severity item is rated from 0 to 4, and each bothersome item from 0 to 10. The total severity score ranges from 0 to 20, and the total bothersome score ranges from 0 to 50. Higher scores indicate worse outcomes.
Outcome Interpretation:
- Improved: Mean ICIQ-FLUTS post-treatment score < pre-treatment score.
- Not Improved: Mean ICIQ-FLUTS post-treatment score ≥ pre-treatment score.
Measured: The patients were monitored closely for 1 and 3 months after treatment.
Secondary outcomes (4)
The impact of urinary storage symptoms on quality of life
- Assess the impact of urinary storage symptoms on quality of life with reference to social effects by Thai version of International Consultation on Incontinence Questionnaire Urinary Incontinence Quality of Life (ICIQ-LUTSqol), which comprises 20 items. The ranges from 19 to 76, with greater values indicating increased impact on quality of life. ICIQ-LUTSqol is a validated Thai adaptation of King's Health Questionnaire (KHQ).
Measured: The patients were monitored closely for 1 and 3 months after treatment.
Global Improvement score
The Global Improvement score is evaluated using the Thai version of the Patient Global Impression of Improvement (PGI-I) scale. This scale is a widely used, patient-reported measure that assesses the patient's overall perception of improvement following a treatment. The PGI-I is typically rated on a 7-point scale, where the minimum value is 1 and the maximum value is 7. On this scale, a score of 1 indicates that the patient feels "very much improved," while a score of 7 indicates that the patient feels "very much worse." Therefore, lower scores on the PGI-I represent better outcomes, reflecting greater improvement in the patient's condition, while higher scores denote worse outcomes, indicating little to no improvement or a decline in the patient's condition.
Measured: The patients were monitored closely for 1 and 3 months after treatment.
Urethral maturation index (UMI) and maturation value (MV)
We will use wet cotton buds coated with normal saline solution (NSS) to gently swab the distal urethra for cytologic preparation. Smear slides will be prepared for cytologic evaluation by immediately immersing them in 95% alcohol for 24 hours and staining them with a Papanicolaou stain. The urethral epithelial cell will be examined under a microscope and classified into three types: parabasal cells, intermediate cells, and superficial cells by an independent cytologist. Two hundred cells were counted at each high-power field which was randomly chosen. Six high-power fields were evaluated and the mean of the cell numbers was calculated. MV is a derived value from the proportion of different cell types and is, therefore, unitless.
Maturation value (MV) = (% parabasal cells × 0) + (% intermediate cells × 0.5) + (% superficial cells × 1.0)
Interpretation:
- MV = 0-49 will indicate low estrogen effect
- MV = 50-64 = moderate estrogen effect
- MV = 65-100 = high estrogen effect
Measured: The patients were monitored closely for 1 and 3 months after treatment.
Vaginal pH
To assess pH, a piece of litmus paper (MQuant® pH-indicator stripe) will be placed on the lateral vaginal wall until moistened. A pH of 4.6 or greater indicates vulvovaginal atrophy (VVA)(31). According to a preliminary double-blinded study in 67 symptomatic postmenopausal women confirmed that atrophic vaginitis is associated with an increase in the lateral wall vaginal pH and this finding is paralleled by similar changes in pH in the urethra. Also, locally applied vaginal conjugated estrogen cream can normalizes the pH in the vagina and urethra Thus, the testing of the vaginal pH serves both as a surrogate for evaluating urethral pH and as a monitor of compliance with treatment.
Measured: The patients were monitored closely for 1 and 3 months after treatment.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jul 2024
- Study start8 Apr 2024
- Primary completion22 Oct 2024
- Study completion31 Oct 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (39)Papers the sponsor has linked to this study.
- Other trials for Lower Urinary Tract SymptomsStudies of the same condition, open and under way.
- More trials run by Mahidol UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 86 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mahidol University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Pornthip Harncharoenkul, MD, Principal investigator, Ramathibodi Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06508944
- Sponsor's protocol ID
- MURA2024/10
- Other IDs
- RF_67069
- Status last verified
- Apr 2025
- First submitted
- 5 Jul 2024
- Last updated
- 20 Apr 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Tomaszewski J. Postmenopausal overactive bladder. Prz Menopauzalny. 2014 Dec;13(6):313-29. doi: 10.5114/pm.2014.47984. Epub 2014 Dec 30.
PubMed 26327873Abrams P, Cardozo L, Fall M, Griffiths D, Rosier P, Ulmsten U, Van Kerrebroeck P, Victor A, Wein A; Standardisation Sub-Committee of the International Continence Society. The standardisation of terminology in lower urinary tract function: report from the standardisation sub-committee of the International Continence Society. Urology. 2003 Jan;61(1):37-49. doi: 10.1016/s0090-4295(02)02243-4. No abstract available.
PubMed 12559262Weber MA, Kleijn MH, Langendam M, Limpens J, Heineman MJ, Roovers JP. Local Oestrogen for Pelvic Floor Disorders: A Systematic Review. PLoS One. 2015 Sep 18;10(9):e0136265. doi: 10.1371/journal.pone.0136265. eCollection 2015.
PubMed 26383760Stewart WF, Van Rooyen JB, Cundiff GW, Abrams P, Herzog AR, Corey R, Hunt TL, Wein AJ. Prevalence and burden of overactive bladder in the United States. World J Urol. 2003 May;20(6):327-36. doi: 10.1007/s00345-002-0301-4. Epub 2002 Nov 15.
PubMed 12811491Iosif CS, Batra S, Ek A, Astedt B. Estrogen receptors in the human female lower uninary tract. Am J Obstet Gynecol. 1981 Dec 1;141(7):817-20. doi: 10.1016/0002-9378(81)90710-9.
PubMed 7198384Chung da J, Bai SW. Roles of sex steroid receptors and cell cycle regulation in pathogenesis of pelvic organ prolapse. Curr Opin Obstet Gynecol. 2006 Oct;18(5):551-4. doi: 10.1097/01.gco.0000242959.63362.1e.
PubMed 16932051Rud T, Andersson KE, Asmussen M, Hunting A, Ulmsten U. Factors maintaining the intraurethral pressure in women. Invest Urol. 1980 Jan;17(4):343-7.
PubMed 7188694Matsubara S, Okada H, Shirakawa T, Gotoh A, Kuno T, Kamidono S. Estrogen levels influence beta-3-adrenoceptor-mediated relaxation of the female rat detrusor muscle. Urology. 2002 Apr;59(4):621-5. doi: 10.1016/s0090-4295(01)01583-7.
PubMed 11927339Shenfeld OZ, McCammon KA, Blackmore PF, Ratz PH. Rapid effects of estrogen and progesterone on tone and spontaneous rhythmic contractions of the rabbit bladder. Urol Res. 1999 Oct;27(5):386-92. doi: 10.1007/s002400050168.
PubMed 10550529Peyronnet B, Mironska E, Chapple C, Cardozo L, Oelke M, Dmochowski R, Amarenco G, Game X, Kirby R, Van Der Aa F, Cornu JN. A Comprehensive Review of Overactive Bladder Pathophysiology: On the Way to Tailored Treatment. Eur Urol. 2019 Jun;75(6):988-1000. doi: 10.1016/j.eururo.2019.02.038. Epub 2019 Mar 26.
PubMed 30922690Chen HY, Lin YN, Chen WC, Wang SJ, Chen CJ, Chen YH. Urethral proteomic analysis in ovariectomized mice administered 17beta-oestradiol replacement therapy. J Obstet Gynaecol. 2017 Aug;37(6):757-765. doi: 10.1080/01443615.2017.1292225. Epub 2017 Mar 28.
PubMed 28350532Johnston SL. Pelvic floor dysfunction in midlife women. Climacteric. 2019 Jun;22(3):270-276. doi: 10.1080/13697137.2019.1568402. Epub 2019 Mar 11.
PubMed 30857432Benness C, Wise BG, Cutner A, et al. Does low dose vaginal oestradiol improve frequency and urgency in postmenopausal women. Int Urogynaecol J. 1992;3:281.
Eriksen PS, Rasmussen H. Low-dose 17 beta-estradiol vaginal tablets in the treatment of atrophic vaginitis: a double-blind placebo controlled study. Eur J Obstet Gynecol Reprod Biol. 1992 Apr 21;44(2):137-44. doi: 10.1016/0028-2243(92)90059-8.
PubMed 1587379Pratt TS, Suskind AM. Management of Overactive Bladder in Older Women. Curr Urol Rep. 2018 Sep 10;19(11):92. doi: 10.1007/s11934-018-0845-5.
PubMed 30203368
Study at a glance
From the registry record, last updated by the sponsor on 20 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy of Vaginal 17β-Estradiol on the Urinary Storage Symptoms in Postmenopausal Women: A Randomized Double-Blind, Placebo-Controlled Study
- ClinicalTrials.gov ID
- NCT06508944
- Acronym / sponsor ID
- MURA2024/10
- Conditions
- Lower Urinary Tract Symptoms, Female Genitourinary Disease, Urinary Stress Incontinence, Urinary Urge Incontinence, Nocturia, Quality of Life
- Keywords
- 17 beta-estradiol, lower urinary tract symptoms, postmenopause, female genitourinary diseases, urethral maturation index, vaginal pH, ICIQ-FLUTS, ICIQ-LUTSqol
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 86 participants (actual)
- Lead sponsor
- Mahidol UniversityUniversity, hospital or other
- Study start
- 8 Apr 2024 (actual)
- Primary completion
- 22 Oct 2024 (actual)
- Study completion
- 31 Oct 2024 (actual)
- First posted
- 18 Jul 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goal of this clinical trial is to evaluate whether vaginal 17β-estradiol effectively treats storage symptoms of lower urinary tract symptoms (LUTS) and enhances quality of life. The main questions it aims to answer are:
- What is the efficacy of vaginal 17β-estradiol treatment compared to placebo in alleviating storage symptoms of LUTS?
- How does vaginal 17β-estradiol treatment affect the urethral maturation index and vaginal pH compared to placebo?
- What impact does vaginal 17β-estradiol treatment have on overall quality of life and patients' perception of global improvement (PGI)?
Participants in the trial will undergo the following procedures:
- Screening procedures at the first visit to exclude correctable causes of LUTS and to complete a bladder diary.
- Visit the clinic at 1-2 weeks for a review of the bladder diary and a check-up. Participants will receive the assigned dosage of vaginal 17β-estradiol or placebo: one vaginal tablet daily for two weeks, followed by one vaginal tablet twice a week for 10 weeks.
- The third and fourth visits (at 4 and 12 weeks after treatment) will involve: completion of bladder diaries, questionnaires, vaginal pH testing, collection of urethral maturation index (UMI), observation of intervention's side effects and monitoring of LUTS symptoms.
Detailed description
- First Visit and Recruitment
Participants will be recruited from the urogynecology clinic, menopause clinic, and urology clinic using hospital and public advertisement. An information sheet in Thai language will be provided to health care providers in the designated outpatient department (OPD) which can ensure the providers convey the correct study information to potential participant. Participants will only be able to enroll into this study one time.
Informed Consent
Individuals with at least one storage symptom of LUTS presenting to clinics in selected OPD will undergo the informed consent process by principal investigator prior to initiating screening procedures. Consent form in Thai language describing in detail the study procedures will be given to the participant privately in a separate room, and extensive discussion of risks and possible benefits of participation in this study will be provided. Participation will be informed that they may withdraw consent at any time throughout the course of this study.
Screening
After documentation of informed consent, principal investigator will interview the participant and perform vital signs and physical examination. The urinalysis will be performed by urinalysis test strip before the start of the study. Screening procedures are as follows;
- Pelvic exam
- Pelvic floor muscle strength measured as Brink scale
- Pelvic Organ Prolapse Quantification (POP-Q), Stress test
- Gynecologic ultrasonography with post-void residual volumes (PVR)
- Urinalysis by urinalysis test strip
- Bladder diary: consecutive three-day diary which the time of each micturition and the volume voided, fluid intake, incontinence episodes, episodes of urgency and sensation will be recorded, as might be the activities performed during or immediately preceding the involuntary loss of urine.
After screening procedure, the appointment will be made for the next visit, which is one or two weeks after first visit.
Bladder diary
The study will incorporate the use of essential diagnostic tool, namely the bladder diary, to assess and monitor the outcomes. These assessments will be administered under the careful supervision of the study investigators. These diagnostic tests play a pivotal role in our research, serving as indispensable instruments for evaluating the progression and ultimate success of the treatment interventions.
II. Second Visit and Randomization
At one or two weeks after 1st visit, the following study procedure will be performed;
- Bladder diary interpretation
- ICIQ-FLUTS questionnaire
- ICIQ-LUTSqol questionnaire
- Vaginal pH
- Urethral maturation index (UMI)
After evaluating all the data collected during the screening process at the initial visit and combining it with the procedures conducted during the second visit, if the woman does not meet all study inclusion or if the woman has an exclusion criterion, she will not be enrolled into this study. A screening log will be kept of all who were evaluated for participation to document who is and is not enrolled and reason for not enrolling in this study.
Women who meet inclusion criteria will be randomized with block randomization technique and a ratio of treatments of 1:1. The sequence generation will be performed under supervision of a senior statistician at the section of Clinical Epidemiology and Biostatistics in Ramathibodi Hospital. The random sequences will be generated using Stata version 18. This is an automated process with no interfere from the investigators. Upon a subject's successful enrollment in the clinical trial following eligibility assessment, principal investigator or research personnel shall provide participants with a comprehensive Thai guidebook for behavior modification which is designed to ensure the harmonization of knowledge and behaviors among all trial participants. This guidebook was developed and published by The International Urogynecological Association (IUGA) and will be distributed by research assistants.
Trial Treatment: Dosage Form, Regimen, Route of Administration
- 17beta-Estradiol 10 mcg (Femiest® Pharma Munster GMBH, Muenster, Germany (ESTRADIOL HEMIHYDRATE 0.0103 milligram, pH 6.94) 17beta-Estradiol will be administered to group A treatment arm intravaginally. The assigned dosage will be one vaginal tablet daily for two weeks then one vaginal tablet twice a week for 10 weeks. Participants will be carefully monitored for any changes in clinical condition in each follow-up visits using logbook. It is important to clarify that the investigators are not using 17beta-Estradiol (Vagifem®) 25 mcg as the study drug. Although 17beta-Estradiol 25 mcg is frequently mentioned in literature reviews and has been historically used for treating vaginal dryness, this drug is currently not available in Thailand. Therefore, the investigators are using 17beta-Estradiol (Femiest®) 10 mcg as an alternative for our study drug. Notably, 17beta-Estradiol 10 mcg has been shown to provide a therapeutic dose equivalent to that of 17beta-Estradiol 25 mcg for treatment, as stated by the FDA. This decision ensures that participants receive an effective and appropriate dosage while adhering to the availability of medications in our region.
- Placebo
Placebo will be administered to group B treatment arms intravaginally. The assigned dosage will be one vaginal tablet daily for two weeks then one vaginal tablet twice a week for 10 weeks. Participants will be carefully monitored for any changes in clinical condition in each follow-up visits. Placebo is produced by Chulalongkorn University Drug and Health Products Innovation \& Promotion Center, Faculty of Pharmaceutical Sciences, Chulalongkorn University. Details for presentation and packing are as follows;
- Appearance: White, round, biconvex with "E" imprint one side
- Weight: 106 - 110 mg
- Hardness: 4.1 - 4.8 kilopond (kp)
- Thickness: 3.26 - 3.3 mm
- Diameter: 6.02 - 6.03 mm
- Disintegration time: 4 min 58sec - 7min 42sec
- pH: 7.18
Placebo contains
- Agglomerated Lactose
- Microcrystalline cellulose PH 102
- Magnesium stearate
Both subject groups will be counseled on potential signs/symptoms of adverse events and post-marketing experience, such as breast pain, peripheral edema, and postmenopausal bleedings. Due to the vaginal administration and minimal systemic absorption, it is unlikely that any clinically relevant drug interactions will occur with 17beta-Estradiol. However, interactions with other locally applied vaginal treatments will be considered and advised to the patients. If a dose is forgotten, participants will be advised that it should be taken as soon as he/she remembers. A double dose should be avoided.
Random allocation
Each participant in the study will receive a prescription for the research drug, an adequate supply to cover a 12-week treatment duration. This drug will be uniformly packaged within identical containers, featuring a unique alphanumeric code and detailed usage instructions on the label, thereby avoiding the inclusion of the original medication name. The data analysis will be performed by a statistician who will be the sole individual privy to the allocation of drug A or drug B to their respective groups. It is essential to note that the statistician will remain unaware of which of the two is the active drug and which is the placebo. Additionally, an independent statistician will maintain a sealed randomization list as a contingency. Allocation will be as follows;
Group A: 17beta-Estradiol 10 mcg (Femiest® Haupt Pharma Munster GMBH, Muenster, Germany (ESTRADIOL HEMIHYDRATE 0.0103 milligram)
Group B: Placebo
III. Third Visit
At four weeks after 2nd visit, the following study procedure will be performed;
- Bladder diary, the participant will be reminded to provide a three-day diary prior to schedule visit date.
- ICIQ-FLUTS questionnaire
- ICIQ-LUTSqol questionnaire
- PGI-I score
- Vaginal pH
- Urethral maturation index (UMI)
Participants will also have clinical evaluation and vital signs measurements evaluated. Compensation for participants will be provided.
IV. Fourth and Final Visit
At eight weeks after 3rd visit, the following study procedure will be performed;
- Pelvic exam
- Pelvic floor muscle strength measured as Brink scale
- Bladder diary, the participant will be reminded to provide a three-day diary prior to schedule visit date.
- ICIQ-FLUTS questionnaire
- ICIQ-LUTSqol questionnaire
- PGI-I score
- Vaginal pH
- Urethral maturation index (UMI)
Participants will also have clinical evaluation and vital signs measurements evaluated. Compensation for participants will be provided.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Group A: Behavioral modifications and vaginal 17beta-estradiol | Experimental | Drug: vaginal 17 beta-estradiol, Behavioral: Behavioral modifications• 17beta-Estradiol 10 mcg + Behavioral modifications |
| Group B: Behavioral modifications + Placebo | Placebo comparator | Drug: Placebo, Behavioral: Behavioral modifications• Placebo + Behavioral modifications |
Who may qualify
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (11 listed)
- Presenting with storage phase symptom score more than/equal to 1 evaluated by the ICIQ-FLUTS questionnaire in these items
- Being natural or surgical menopause for more than 1 year
- Absence of urinary tract infection or other identifiable cause
- Not using hormone replacement therapy or any route of estrogen within 4 weeks
- Never undergone onabotulinumtoxinA therapy, percutaneous tibial nerve stimulation (PTNS), or neuromodulation for overactive bladder (OAB) treatment
Key exclusion criteria (9 listed)
- Contraindication for estrogen therapy: undiagnosed abnormal vaginal bleeding, previous thromboembolic event, breast cancer, gynecologic/genitourinary malignancy, active liver disease
- Pelvic organ prolapse of anterior compartment stage III and IV
- Immunocompromised patient or taking immunosuppressant drug
- History of antibiotics drug use within the past 7 days
- History of bladder outlet obstruction
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| vaginal 17 beta-estradiolAlso: Femiest, ESTRADIOL HEMIHYDRATE, vagifem* Femiest® Haupt Pharma Munster GMBH, Muenster, Germany * The assigned dosage will be one vaginal tablet daily for two weeks then one vaginal tablet twice a week for 10 weeks. | Drug | Group A: Behavioral modifications and vaginal 17beta-estradiol |
| PlaceboAlso: Agglomerated Lactose, Microcrystalline cellulose PH 102, Magnesium stearate* Placebo is produced by Chulalongkorn University Drug and Health Products Innovation \& Promotion Center. * The assigned dosage will be one vaginal tablet daily for two weeks then one vaginal tablet twice a week for 10 weeks. | Drug | Group B: Behavioral modifications + Placebo |
| Behavioral modificationsBehavioral modifications for women with storage symptoms of lower urinary tract symptoms (LUTS) involve strategies such as regulating fluid intake, avoiding bladder irritants, practicing bladder training techniques (scheduled and delayed voiding), performing pelvic floor muscle exercises, managing weight, increasing dietary fiber, maintaining a bladder diary, setting a regular voiding schedule, utilizing stress management techniques, and educating patients about LUTS. | Behavioural | Group A: Behavioral modifications and vaginal 17beta-estradiol, Group B: Behavioral modifications + Placebo |
Primary outcome
Storage symptom improvement
Time frame: The patients were monitored closely for 1 and 3 months after treatment.
Storage Symptom Improvement: This will be evaluated using the International Consultation on Incontinence Questionnaire-Female Lower Urinary Tract Symptoms (ICIQ-FLUTS), validated in Thai. The questionnaire includes 5 items addressing storage symptoms: * 2a) Nocturia * 3a) Urgency * 5a) Daytime frequency * 9a) Urgency urinary incontinence (UUI) * 11a) Stress urinary incontinence (SUI) Each severity item is rated from 0 to 4, and each bothersome item from 0 to 10. The total severity score ranges from 0 to 20, and the total bothersome score ranges from 0 to 50. Higher scores indicate worse outcomes. Outcome Interpretation: * Improved: Mean ICIQ-FLUTS post-treatment score < pre-treatment score. * Not Improved: Mean ICIQ-FLUTS post-treatment score ≥ pre-treatment score.
4 secondary outcomes
The impact of urinary storage symptoms on quality of life
Time frame: The patients were monitored closely for 1 and 3 months after treatment.
Global Improvement score
Time frame: The patients were monitored closely for 1 and 3 months after treatment.
Urethral maturation index (UMI) and maturation value (MV)
Time frame: The patients were monitored closely for 1 and 3 months after treatment.
Vaginal pH
Time frame: The patients were monitored closely for 1 and 3 months after treatment.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Apr 2025.
- Background: PubMed 26327873Tomaszewski J. Postmenopausal overactive bladder. Prz Menopauzalny. 2014 Dec;13(6):313-29. doi: 10.5114/pm.2014.47984. Epub 2014 Dec 30.
- Background: PubMed 12559262Abrams P, Cardozo L, Fall M, Griffiths D, Rosier P, Ulmsten U, Van Kerrebroeck P, Victor A, Wein A; Standardisation Sub-Committee of the International Continence Society. The standardisation of terminology in lower urinary tract function: report from the standardisation sub-committee of the International Continence Society. Urology. 2003 Jan;61(1):37-49. doi: 10.1016/s0090-4295(02)02243-4. No abstract available.
- Background: PubMed 26383760Weber MA, Kleijn MH, Langendam M, Limpens J, Heineman MJ, Roovers JP. Local Oestrogen for Pelvic Floor Disorders: A Systematic Review. PLoS One. 2015 Sep 18;10(9):e0136265. doi: 10.1371/journal.pone.0136265. eCollection 2015.
- Background: PubMed 12811491Stewart WF, Van Rooyen JB, Cundiff GW, Abrams P, Herzog AR, Corey R, Hunt TL, Wein AJ. Prevalence and burden of overactive bladder in the United States. World J Urol. 2003 May;20(6):327-36. doi: 10.1007/s00345-002-0301-4. Epub 2002 Nov 15.
- Background: PubMed 7198384Iosif CS, Batra S, Ek A, Astedt B. Estrogen receptors in the human female lower uninary tract. Am J Obstet Gynecol. 1981 Dec 1;141(7):817-20. doi: 10.1016/0002-9378(81)90710-9.
- Background: PubMed 16932051Chung da J, Bai SW. Roles of sex steroid receptors and cell cycle regulation in pathogenesis of pelvic organ prolapse. Curr Opin Obstet Gynecol. 2006 Oct;18(5):551-4. doi: 10.1097/01.gco.0000242959.63362.1e.
- Background: PubMed 7188694Rud T, Andersson KE, Asmussen M, Hunting A, Ulmsten U. Factors maintaining the intraurethral pressure in women. Invest Urol. 1980 Jan;17(4):343-7.
- Background: PubMed 11927339Matsubara S, Okada H, Shirakawa T, Gotoh A, Kuno T, Kamidono S. Estrogen levels influence beta-3-adrenoceptor-mediated relaxation of the female rat detrusor muscle. Urology. 2002 Apr;59(4):621-5. doi: 10.1016/s0090-4295(01)01583-7.
- Background: PubMed 10550529Shenfeld OZ, McCammon KA, Blackmore PF, Ratz PH. Rapid effects of estrogen and progesterone on tone and spontaneous rhythmic contractions of the rabbit bladder. Urol Res. 1999 Oct;27(5):386-92. doi: 10.1007/s002400050168.
- Background: PubMed 30922690Peyronnet B, Mironska E, Chapple C, Cardozo L, Oelke M, Dmochowski R, Amarenco G, Game X, Kirby R, Van Der Aa F, Cornu JN. A Comprehensive Review of Overactive Bladder Pathophysiology: On the Way to Tailored Treatment. Eur Urol. 2019 Jun;75(6):988-1000. doi: 10.1016/j.eururo.2019.02.038. Epub 2019 Mar 26.
- Background: PubMed 28350532Chen HY, Lin YN, Chen WC, Wang SJ, Chen CJ, Chen YH. Urethral proteomic analysis in ovariectomized mice administered 17beta-oestradiol replacement therapy. J Obstet Gynaecol. 2017 Aug;37(6):757-765. doi: 10.1080/01443615.2017.1292225. Epub 2017 Mar 28.
- Background: PubMed 30857432Johnston SL. Pelvic floor dysfunction in midlife women. Climacteric. 2019 Jun;22(3):270-276. doi: 10.1080/13697137.2019.1568402. Epub 2019 Mar 11.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Pornthip Harncharoenkul, MD principal investigator
Ramathibodi Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing vaginal 17 beta-estradiol and Behavioral modifications in people with Lower Urinary Tract Symptoms and Female Genitourinary Disease, run by Mahidol University at 1 site in Thailand.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Thailand. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Storage symptom improvement (time frame: The patients were monitored closely for 1 and 3 months after treatment.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06508944, which also lists 39 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Apr 2025.