MenopausePhase 4NCT03336437
Estrogen and the Urogenital Microbiome in GSM
A Phase 4 study testing Estradiol vaginal ring in people with Menopause, run by Oregon Health and Science University at 1 site in United States.
Trial summary
This is a study of how local estrogen treatment affects the microbiome of the vagina and bladder in postmenopausal women experiencing symptoms as part of "Genitourinary Syndrome of Menopause." The goal is to understand more about the underlying microbial changes occurring in menopause and whether these are reversible… Read more about this study
- Who is it for?
- Ages 40 to 89 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Menopause
- What is being tested?
- Estradiol vaginal ring
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 40 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Feb 2018to 23 Aug 2019
- 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 40 to 89 years
- Women only
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Postmenopausal female
- Generally healthy
Who cannot join
- Known allergy or contraindications to the intervention
- Use of hormone therapy in the last 3 months
- Current tamoxifen use
- Currently using vaginal pessary
- History of breast cancer or BRCA mutation
- History of uterine, ovarian or cervical cancer
Show all 12Show fewer
- History of deep vein thrombosis or pulmonary embolism
- History of stroke or myocardial infarction
- Known thrombophilic disorder (Protein S deficiency, Protein C deficiency, antithrombin deficiency)
- Known liver disease
- Use of systemic or vaginal antibiotics in the last 2 months
- Urinary tract or vaginal infection in the last 2 months
Trial locations and contacts
1 site in 1 country.
United States1 site
Women's Health Research Unit at Oregon Health and Science University
Portland, Oregon, 97239
About this study
Official title: The Impact of Local Estrogen on the Urogenital Microbiome in Genitourinary Syndrome of Menopause (GSM)
This is a study of how local estrogen treatment affects the microbiome of the vagina and bladder in postmenopausal women experiencing symptoms as part of "Genitourinary Syndrome of Menopause." The goal is to understand more about the underlying microbial changes occurring in menopause and whether these are reversible with estrogen.
Read the detailed description
Women who have undergone menopause almost ubiquitously experience pelvic complaints at some point in the postmenopausal period. This is most commonly vaginal dryness and discomfort during sexual intercourse. From previous studies, we know that as estrogen levels decrease in menopause, changes occur in the local urogenital tract that include thinning of the vaginal epithelium, an increase in pH and an alteration of the composition of the local bacterial community, including a decrease in the typically predominant species of bacteria lactobacilli. In conjunction with declining estrogen levels, a subset of postmenopausal women experience bothersome lower urinary tract symptoms such as burning with urination, urinary urgency, incontinence and recurrent urinary tract infections. These symptoms are commonly underreported, under-treated, and have been associated with reduced quality of life and decreased productivity in menopause. "Genitourinary Syndrome of Menopause" (GSM) is a term adapted to be more inclusive of these lower urinary tract symptoms in an effort to reduce delays in evaluation and treatment. It remains controversial whether these symptoms relate directly to estrogen deprivation or are part of the "natural" aging process. Mainstay therapy includes vaginal lubricants and local estrogen therapy. Though treatment with local estrogen improves both vaginal dryness as well as urinary symptoms, the mechanism is not well understood.
Additionally, there is a subset of women who do not respond to estrogen treatment or have contraindications to estrogen use. Recent research efforts have been exploring the potential role that the microbiome may play in female pelvic discomfort and dysfunction. Unlike the vagina, the bladder has historically been considered to be a sterile environment, with the presence of bacteria implying infection. However, recent research has helped to elucidate that, similar to the skin, vagina and gastrointestinal tract, a resident microbial community or "microbiome" exists within the female bladder. Disturbances in the urinary microbial community have been correlated with conditions such as painful bladder syndrome, overactive bladder and urge urinary incontinence. These conditions have considerable symptom overlap with those seen in postmenopausal women who are experiencing GSM and may be considered to be on the same continuum.
Though microbiome research over the last decade has accelerated our understanding of the role that organisms play in health and disease, the urinary microbiome remains poorly defined. Data from ongoing research suggests that the urinary microbiome of pre- and postmenopausal women differ, which would suggest that hormone status may play a role in maintaining the microbial milieu. This research has helped us to better understand how the urinary microbiome varies under normal conditions. In order to better understand the role that estrogen plays in maintaining the bladder and vaginal flora, this study aims to characterize the effect of local estrogen on the urinary and vaginal microbiomes (together termed the "urogenital microbiome") in postmenopausal women.
- Conditions
- Menopause
- Being tested
- Estradiol vaginal ring, Placebo vaginal ring
- Keywords
- Menopause, Vaginal dryness, Vaginal atrophy, Postmenopause, Estrogen, Urinary microbiome, Estradiol vaginal ring, Genitourinary Syndrome of Menopause, Vaginal microbiome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Estradiol vaginal ringDrug
Estradiol 2mg vaginal ring
Placebo vaginal ringOther
Silicone vaginal ring without any active estradiol
| Study group | Role | What they receive |
|---|---|---|
| Estrogen Vaginal Ring | Active comparator | At the time of initial study visit, a estrogen vaginal ring (Estring) will be placed. Participants will retain this ring for 12 weeks. Receives: Drug: Estradiol vaginal ring |
| Inactive Vaginal Placebo Ring | Placebo comparator | At the time of initial study visit, a placebo vaginal ring will be placed. Participants will retain this ring for 12 weeks. Receives: Other: Placebo vaginal ring |
What is being measured
The primary outcome is the main question the study is designed to answer.
Urinary Microbiome: change in the relative abundance of urinary lactobacillus between baseline and 12 weeks post intervention
Investigators will collect catheterized urine samples from participants at time of enrollment in the study and again after 12 weeks of their assigned vaginal ring intervention. Bacteria will be extracted from the urine and the resident microbial community will be characterized by amplifying the bacterial 16S ribosomal RNA gene via PCR. The de-identified samples containing amplified 16S DNA will be sequenced using Illumina MiSeq. The genetic sequences will be processed to generate a table of bacterial identity and relative quantity. Statistical tests designed for microbiome data will be used in order to determine differences between the relative amount of lactobacillus (via the lactobacillus ratio) before and after the intervention.
Measured: Baseline to 12 weeks post-intervention
Secondary outcomes (1)
Change in prevalence of GSM symptoms
Validated symptom questionnaires will be collected at baseline and again after 12 weeks of assigned intervention to assess common symptoms associated with Genitourinary Syndrome of Menopause (GSM), such as vaginal dryness, painful intercourse and urinary urgency.
Measured: Baseline to 12 weeks post-intervention
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Nov 2017
- Study start1 Feb 2018
- Primary completion23 Aug 2019
- Study completion23 Aug 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for MenopauseStudies of the same condition, open and under way.
- More trials run by Oregon Health and Science 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
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- Oregon Health and Science University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jennifer Lillemon, Oregon Health and Science University
- Investigators
- Jennifer Lillemon, Principal investigator, Oregon Health and Science University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03336437
- Sponsor's protocol ID
- OHSU IRB# 17056
- Status last verified
- Sep 2019
- First submitted
- 2 Nov 2017
- Last updated
- 22 Nov 2019
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Lillemon JN, Karstens L, Nardos R, Garg B, Boniface ER, Gregory WT. The Impact of Local Estrogen on the Urogenital Microbiome in Genitourinary Syndrome of Menopause: A Randomized-Controlled Trial. Female Pelvic Med Reconstr Surg. 2022 Jun 1;28(6):e157-e162. doi: 10.1097/SPV.0000000000001170. Epub 2022 Apr 15.
PubMed 35420551
Study at a glance
From the registry record, last updated by the sponsor on 22 Nov 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Impact of Local Estrogen on the Urogenital Microbiome in Genitourinary Syndrome of Menopause (GSM)
- ClinicalTrials.gov ID
- NCT03336437
- Acronym / sponsor ID
- OHSU IRB# 17056
- Conditions
- Menopause
- Keywords
- Menopause, Vaginal dryness, Vaginal atrophy, Postmenopause, Estrogen, Urinary microbiome, Estradiol vaginal ring, Genitourinary Syndrome of Menopause
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- Oregon Health and Science UniversityUniversity, hospital or other
- Study start
- 1 Feb 2018 (actual)
- Primary completion
- 23 Aug 2019 (actual)
- Study completion
- 23 Aug 2019 (actual)
- First posted
- 8 Nov 2017 (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.
This is a study of how local estrogen treatment affects the microbiome of the vagina and bladder in postmenopausal women experiencing symptoms as part of "Genitourinary Syndrome of Menopause." The goal is to understand more about the underlying microbial changes occurring in menopause and whether these are reversible with estrogen.
Detailed description
Women who have undergone menopause almost ubiquitously experience pelvic complaints at some point in the postmenopausal period. This is most commonly vaginal dryness and discomfort during sexual intercourse. From previous studies, we know that as estrogen levels decrease in menopause, changes occur in the local urogenital tract that include thinning of the vaginal epithelium, an increase in pH and an alteration of the composition of the local bacterial community, including a decrease in the typically predominant species of bacteria lactobacilli. In conjunction with declining estrogen levels, a subset of postmenopausal women experience bothersome lower urinary tract symptoms such as burning with urination, urinary urgency, incontinence and recurrent urinary tract infections. These symptoms are commonly underreported, under-treated, and have been associated with reduced quality of life and decreased productivity in menopause. "Genitourinary Syndrome of Menopause" (GSM) is a term adapted to be more inclusive of these lower urinary tract symptoms in an effort to reduce delays in evaluation and treatment. It remains controversial whether these symptoms relate directly to estrogen deprivation or are part of the "natural" aging process. Mainstay therapy includes vaginal lubricants and local estrogen therapy. Though treatment with local estrogen improves both vaginal dryness as well as urinary symptoms, the mechanism is not well understood.
Additionally, there is a subset of women who do not respond to estrogen treatment or have contraindications to estrogen use. Recent research efforts have been exploring the potential role that the microbiome may play in female pelvic discomfort and dysfunction. Unlike the vagina, the bladder has historically been considered to be a sterile environment, with the presence of bacteria implying infection. However, recent research has helped to elucidate that, similar to the skin, vagina and gastrointestinal tract, a resident microbial community or "microbiome" exists within the female bladder. Disturbances in the urinary microbial community have been correlated with conditions such as painful bladder syndrome, overactive bladder and urge urinary incontinence. These conditions have considerable symptom overlap with those seen in postmenopausal women who are experiencing GSM and may be considered to be on the same continuum.
Though microbiome research over the last decade has accelerated our understanding of the role that organisms play in health and disease, the urinary microbiome remains poorly defined. Data from ongoing research suggests that the urinary microbiome of pre- and postmenopausal women differ, which would suggest that hormone status may play a role in maintaining the microbial milieu. This research has helped us to better understand how the urinary microbiome varies under normal conditions. In order to better understand the role that estrogen plays in maintaining the bladder and vaginal flora, this study aims to characterize the effect of local estrogen on the urinary and vaginal microbiomes (together termed the "urogenital microbiome") in postmenopausal women.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Estrogen Vaginal Ring | Active comparator | Drug: Estradiol vaginal ringAt the time of initial study visit, a estrogen vaginal ring (Estring) will be placed. Participants will retain this ring for 12 weeks. |
| Inactive Vaginal Placebo Ring | Placebo comparator | Other: Placebo vaginal ringAt the time of initial study visit, a placebo vaginal ring will be placed. Participants will retain this ring for 12 weeks. |
Who may qualify
- Ages
- 40 to 89 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Postmenopausal female
- Generally healthy
Key exclusion criteria (12 listed)
- Known allergy or contraindications to the intervention
- Use of hormone therapy in the last 3 months
- Current tamoxifen use
- Currently using vaginal pessary
- History of breast cancer or BRCA mutation
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 |
|---|---|---|
| Estradiol vaginal ringEstradiol 2mg vaginal ring | Drug | Estrogen Vaginal Ring |
| Placebo vaginal ringSilicone vaginal ring without any active estradiol | Other | Inactive Vaginal Placebo Ring |
Primary outcome
Urinary Microbiome: change in the relative abundance of urinary lactobacillus between baseline and 12 weeks post intervention
Time frame: Baseline to 12 weeks post-intervention
Investigators will collect catheterized urine samples from participants at time of enrollment in the study and again after 12 weeks of their assigned vaginal ring intervention. Bacteria will be extracted from the urine and the resident microbial community will be characterized by amplifying the bacterial 16S ribosomal RNA gene via PCR. The de-identified samples containing amplified 16S DNA will be sequenced using Illumina MiSeq. The genetic sequences will be processed to generate a table of bacterial identity and relative quantity. Statistical tests designed for microbiome data will be used in order to determine differences between the relative amount of lactobacillus (via the lactobacillus ratio) before and after the intervention.
1 secondary outcome
Change in prevalence of GSM symptoms
Time frame: Baseline to 12 weeks post-intervention
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 22 Nov 2019.
- Derived from this study: PubMed 35420551Lillemon JN, Karstens L, Nardos R, Garg B, Boniface ER, Gregory WT. The Impact of Local Estrogen on the Urogenital Microbiome in Genitourinary Syndrome of Menopause: A Randomized-Controlled Trial. Female Pelvic Med Reconstr Surg. 2022 Jun 1;28(6):e157-e162. doi: 10.1097/SPV.0000000000001170. Epub 2022 Apr 15.
- 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.
Jennifer Lillemon principal investigator
Oregon Health and Science University
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 Estradiol vaginal ring in people with Menopause, run by Oregon Health and Science University at 1 site in United States.
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 2 inclusion and 12 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 22 Nov 2019. 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 United States. 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?
Urinary Microbiome: change in the relative abundance of urinary lactobacillus between baseline and 12 weeks post intervention (time frame: Baseline to 12 weeks post-intervention). 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 NCT03336437, which also lists 1 linked publication.
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 22 Nov 2019.