ClinicalTrials.gg
CompletedNCT03336437Updated Nov 22, 2019

Estrogen and the Urogenital Microbiome in GSM

A Phase 4 interventional study of Estradiol vaginal ring and Placebo vaginal ring in Menopause, sponsored by Oregon Health and Science University. Completed at 1 site in United States. Open to female participants aged 40 Years to 89 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2019-11-22.

Sponsored by Oregon Health and Science University · Phase 4, Interventional, and Basic science

Phase
Phase 4
Study type
Interventional
Enrollment
40
Allocation
Randomized
Ages
40 Years to 89 Years
Sex
Female
01

Study 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 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.

02

Conditions studied

  • Menopause

Keywords

  • Menopause
  • Vaginal dryness
  • Vaginal atrophy
  • Postmenopause
  • Estrogen
  • Urinary microbiome
  • Estradiol vaginal ring
  • Genitourinary Syndrome of Menopause
  • Vaginal microbiome
03

In context

Lead sponsor

Oregon Health and Science University is the lead sponsor of 696 studies on the registry; 131 are open to participants now.

Of its 52 completed or terminated interventional studies of FDA-regulated products, 39 (75%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
40 Years to 89 Years
Sexes eligible
Female
Accepts healthy volunteers
Yes

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.

Inclusion criteria

  • female
  • Generally healthy

Exclusion criteria

Exclusion Criteria:

  • Known allergy or 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
  • 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
Terms in these criteria, in plain language(2)

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.

Postmenopausal

Periods have stopped for good: usually no period for 12 months in a row without another medical reason, sometimes confirmed by a blood test (FSH).

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.

05

Study design

Phase
Phase 4
Primary purpose
Basic science
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Single (Participant)
Enrollment
40 participants (actual)

Study arms

  • Active comparator
    Estrogen Vaginal Ring

    At the time of initial study visit, a estrogen vaginal ring (Estring) will be placed. Participants will retain this ring for 12 weeks.

    Drug: Estradiol vaginal ring

  • Placebo comparator
    Inactive Vaginal Placebo Ring

    At the time of initial study visit, a placebo vaginal ring will be placed. Participants will retain this ring for 12 weeks.

    Other: Placebo vaginal ring

Interventions

  • Estradiol 2mg vaginal ring

  • OtherPlacebo vaginal ring

    Silicone vaginal ring without any active estradiol

06

What researchers measure

Primary outcomes

  1. 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.

    Time frame: 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.

    Time frame: Baseline to 12 weeks post-intervention

07

Study locations

1 site
  • Women's Health Research Unit at Oregon Health and Science University
    Portland, Oregon 97239, United States
08

References and documents

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 ↗

Individual participant data

Plan to share: No

09

Timeline

Tracking since Sep 25, 2026
ElapsedEstimatedEstimated, not yet reached

Ran from Feb 2018 to primary completion in Aug 2019, 18 months.

How these figures are worked out, and which studies are left out of them.

Registered
Nov 2, 2017
First posted
Nov 8, 2017
StartActual
Feb 1, 2018
Primary completionActual
Aug 23, 2019
CompletionActual
Aug 23, 2019
Last update
Nov 22, 2019
What these dates mean
Start.
When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.
When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.
When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.
Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.
No changes since tracking began. The registry record was last updated on Nov 22, 2019, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT03336437
Responsible party
Jennifer Lillemon (House Officer, Oregon Health and Science University) — Principal investigator
First posted
Nov 8, 2017
Start date
Feb 1, 2018
Primary completion
Aug 23, 2019
Completion
Aug 23, 2019
Last update
Nov 22, 2019

Study contacts

Jennifer Lillemon
principal investigator · Oregon Health and Science University

Oversight

Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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Studies of the drug tested here: Estradiol Vaginal Ring

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