Estrogen and the Urogenital Microbiome in GSM

Menopause Clinical Trial

Official title:

The Impact of Local Estrogen on the Urogenital Microbiome in Genitourinary Syndrome of Menopause (GSM)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03336437
• Other study ID #: OHSU IRB# 17056
• Status: Completed
• Phase: Phase 4
• Start date: February 1, 2018
• Est. completion date: August 23, 2019

Study information

• Verified date: September 2019
• Source: Oregon Health and Science University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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 with estrogen.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: August 23, 2019
• Est. primary completion date: August 23, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 40 Years to 89 Years

Eligibility

Inclusion Criteria:

• Postmenopausal female

• Generally healthy

Exclusion Criteria:

• 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

• 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

Related Conditions & MeSH terms

• Menopause

Intervention

Drug:
• Estradiol vaginal ring
Estradiol 2mg vaginal ring

Other:
• Placebo vaginal ring
Silicone vaginal ring without any active estradiol

Locations

Country	Name	City	State
United States	Women's Health Research Unit at Oregon Health and Science University	Portland	Oregon

Sponsors (1)

Lead Sponsor	Collaborator
Oregon Health and Science University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Baseline to 12 weeks post-intervention
Secondary	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.	Baseline to 12 weeks post-intervention