Estrogen and the Urogenital Microbiome in GSM

NCT ID: NCT03336437

Last Updated: 2019-11-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-02-01
• Study Completion Date: 2019-08-23

Brief 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.

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: SINGLE

Study Groups

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.

Group Type: ACTIVE_COMPARATOR

Estradiol vaginal ring

Intervention Type: DRUG

Estradiol 2mg vaginal ring

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.

Group Type: PLACEBO_COMPARATOR

Placebo vaginal ring

Intervention Type: OTHER

Silicone vaginal ring without any active estradiol

Interventions

Estradiol vaginal ring

Estradiol 2mg vaginal ring

Intervention Type: DRUG

Placebo vaginal ring

Silicone vaginal ring without any active estradiol

Intervention Type: OTHER

Eligibility Criteria

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

• Minimum Eligible Age: 40 Years
• Maximum Eligible Age: 89 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: Yes

Sponsors

Oregon Health and Science University

OTHER

Sponsor Role: lead

Responsible Party

Jennifer Lillemon

House Officer

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jennifer Lillemon

Role: PRINCIPAL_INVESTIGATOR

Oregon Health and Science University

Locations

Women's Health Research Unit at Oregon Health and Science University

Portland, Oregon, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 35420551 (View on PubMed)

Other Identifiers

OHSU IRB# 17056

Identifier Type: -

Identifier Source: org_study_id