A Phase 4 interventional study of vaginal 17 beta-estradiol and Placebo in Lower Urinary Tract Symptoms, Female Genitourinary Disease and Urinary Stress Incontinence, sponsored by Mahidol University. Completed at 1 site in Thailand. Open to female participants. Per ClinicalTrials.gov, last updated 2025-04-20.
Sponsored by Mahidol University · Phase 4, Interventional, and Treatment
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:
Participants in the trial will undergo the following procedures:
I. 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;
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;
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 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;
Placebo contains
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;
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;
Participants will also have clinical evaluation and vital signs measurements evaluated. Compensation for participants will be provided.
416 studies on the registry are indexed under Lower Urinary Tract Symptoms; 110 are open to participants now.
This study's enrollment of 86 is below the median of 100 across 272 interventional studies indexed under Lower Urinary Tract Symptoms.
Browse Lower Urinary Tract Symptoms studies →Mahidol University is the lead sponsor of 747 studies on the registry; 119 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Presenting with storage phase symptom score more than/equal to 1 evaluated by the ICIQ-FLUTS questionnaire in these items
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Immunosuppression
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
• 17beta-Estradiol 10 mcg + Behavioral modifications
Drug: vaginal 17 beta-estradiol · Behavioral: Behavioral modifications
• Placebo + Behavioral modifications
Drug: Placebo · Behavioral: Behavioral modifications
* 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.
Also known as: Femiest, ESTRADIOL HEMIHYDRATE, vagifem
* 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.
Also known as: Agglomerated Lactose, Microcrystalline cellulose PH 102, Magnesium stearate
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.
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.
Time frame: The patients were monitored closely for 1 and 3 months after treatment.
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).
Time frame: 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.
Time frame: 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
Time frame: 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.
Time frame: The patients were monitored closely for 1 and 3 months after treatment.
PDFs hosted by the registry, ClinicalTrials.gov.
Plan to share: No
Ran from Apr 2024 to primary completion in Oct 2024, 6 months.
Of 18 phase 4 interventional studies under Lower Urinary Tract Symptoms, half reached primary completion within 23 months of starting (the median), counting those still running; a quarter within 9 and three quarters within 29. This study's 6 months is below that.
How these figures are worked out, and which studies are left out of them.
This study is completed, as verified in Apr 2025. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Studies of the drug tested here: Estradiol
Lower Urinary Tract Symptoms →