Changes in Neighbouring Microbiota in Genitourinary Syndrome

NCT06633705 | Completed Phase 4

• 1 other identifier: 2023.049.IRB1.012
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 1

Brief Summary

Genitourinary syndrome (GUS) is a disease seen in menopause, which significantly reduces the quality of life of patients. Microbiota studies in GUS are mostly related to vaginal microbiota. However, although urinary problems are also common in GUS, there are less studies on urobiome and no studies on periurethral microbiota. It is recently shown that especially in patients with dyspareunia vaginal microbiota mostly consists of Streptococcus species. As periurethral tissues are close to the skin it is reasonable to think that periurethra and vaginal opening may be colonised by aerobic bacteria which causes the symptoms like burning sensation and dyspareunia. The hypothesis of the study is that vaginal dysbiosis and related aerobic bacteria that become dominant in the periurethral microbiota may be responsible for the emergence of symptoms in menopausal patients with genitourinary syndrome. Changes in the vaginal microbiota with vaginal estrogen therapy will lead to changes in the urobiome and periurethral microbiota. Our aim is to determine the vaginal, periurethral and urinary microbiota content of menopausal women with genitourinary syndrome, to determine the effect of local estrogen therapy on them, and to examine whether there is a difference between these 3 microbiota.

Conditions

Genitourinary Syndrome of Menopause

Keywords

Genitourinary Syndrome of Menopause; vaginal microbiota; periurethral microbiota; urobiome

Outcome Measures

Primary Outcomes (1)

• Vaginal, periurethral and urinary bladder microbiota

  Microbiota contents of 3 areas (vagina, periurethra and bladder) will be obtain and compared to each other

  3 months

Study Arms (4)

GUS-estriol

EXPERIMENTAL

Patients with GUS symptoms and examination findings, who are treated with vaginal oestrogen cream

Drug: Vaginal Cream with Applicator

GUS-control

NO INTERVENTION

Patients with GUS symptoms and examination findings

Control M

NO INTERVENTION

Patients in menopause who doesn't have any GUS symptoms nor examination findings

Control AV

NO INTERVENTION

Patients in menopause who doesn't have any GUS symptoms but have examination findings

Interventions

Vaginal Cream with Applicator DRUG

Vaginal Cream that contains estriol (1mg estriol in 1 g cream)

GUS-estriol

Eligibility Criteria

• Age: 40 Years+
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients who have been in menopause for at least 1 year
• Patients with symptoms of genitourinary syndrome (those with symptoms such as vaginal dryness, frequent urination, burning sensation during urination, pain during intercourse)

You may not qualify if:

• Patients with severe overactive bladder symptoms
• Patients receiving systemic hormone replacement therapy or local estrogen therapy or have received it within the last 3 months
• Patients using vaginal probiotic products
• Patients with advanced pelvic organ prolapse
• Patients with a history of estrogen-dependent breast or endometrial cancer
• Patients allergic to local estrogen
• Patients with urinary tract infection at first presentation or patients who have used antibiotics within the last 2 weeks

Sponsors & Collaborators

• Koc University Hospital: lead

Study Sites (1)

Koc University Hospital

Istanbul, 34110, Turkey (Türkiye)

Location

Related Publications (14)

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  PMID: 25033265 BACKGROUND

• Mitchell CM, Reed SD, Diem S, Larson JC, Newton KM, Ensrud KE, LaCroix AZ, Caan B, Guthrie KA. Efficacy of Vaginal Estradiol or Vaginal Moisturizer vs Placebo for Treating Postmenopausal Vulvovaginal Symptoms: A Randomized Clinical Trial. JAMA Intern Med. 2018 May 1;178(5):681-690. doi: 10.1001/jamainternmed.2018.0116.

  PMID: 29554173 BACKGROUND

• Price TK, Wolff B, Halverson T, Limeira R, Brubaker L, Dong Q, Mueller ER, Wolfe AJ. Temporal Dynamics of the Adult Female Lower Urinary Tract Microbiota. mBio. 2020 Apr 21;11(2):e00475-20. doi: 10.1128/mBio.00475-20.

  PMID: 32317321 BACKGROUND

• Ravel J, Brotman RM, Gajer P, Ma B, Nandy M, Fadrosh DW, Sakamoto J, Koenig SS, Fu L, Zhou X, Hickey RJ, Schwebke JR, Forney LJ. Daily temporal dynamics of vaginal microbiota before, during and after episodes of bacterial vaginosis. Microbiome. 2013 Dec 2;1(1):29. doi: 10.1186/2049-2618-1-29.

  PMID: 24451163 BACKGROUND

• Ravel J, Gajer P, Abdo Z, Schneider GM, Koenig SS, McCulle SL, Karlebach S, Gorle R, Russell J, Tacket CO, Brotman RM, Davis CC, Ault K, Peralta L, Forney LJ. Vaginal microbiome of reproductive-age women. Proc Natl Acad Sci U S A. 2011 Mar 15;108 Suppl 1(Suppl 1):4680-7. doi: 10.1073/pnas.1002611107. Epub 2010 Jun 3.

  PMID: 20534435 BACKGROUND

• Siddiqui H, Nederbragt AJ, Lagesen K, Jeansson SL, Jakobsen KS. Assessing diversity of the female urine microbiota by high throughput sequencing of 16S rDNA amplicons. BMC Microbiol. 2011 Nov 2;11:244. doi: 10.1186/1471-2180-11-244.

  PMID: 22047020 BACKGROUND

• Zhang R, Daroczy K, Xiao B, Yu L, Chen R, Liao Q. Qualitative and semiquantitative analysis of Lactobacillus species in the vaginas of healthy fertile and postmenopausal Chinese women. J Med Microbiol. 2012 May;61(Pt 5):729-739. doi: 10.1099/jmm.0.038687-0. Epub 2012 Feb 2.

  PMID: 22301614 BACKGROUND

• Thomas-White K, Taege S, Limeira R, Brincat C, Joyce C, Hilt EE, Mac-Daniel L, Radek KA, Brubaker L, Mueller ER, Wolfe AJ. Vaginal estrogen therapy is associated with increased Lactobacillus in the urine of postmenopausal women with overactive bladder symptoms. Am J Obstet Gynecol. 2020 Nov;223(5):727.e1-727.e11. doi: 10.1016/j.ajog.2020.08.006. Epub 2020 Aug 11.

  PMID: 32791124 BACKGROUND

• Waetjen LE, Crawford SL, Gajer P, Brooks MM, Gold EB, Reed BD, Hess R, Ravel J. Relationships between the vaginal microbiota and genitourinary syndrome of menopause symptoms in postmenopausal women: the Study of Women's Health Across the Nation. Menopause. 2023 Nov 1;30(11):1073-1084. doi: 10.1097/GME.0000000000002263. Epub 2023 Oct 2.

  PMID: 37788422 BACKGROUND

• The NAMS 2020 GSM Position Statement Editorial Panel. The 2020 genitourinary syndrome of menopause position statement of The North American Menopause Society. Menopause. 2020 Sep;27(9):976-992. doi: 10.1097/GME.0000000000001609.

  PMID: 32852449 BACKGROUND

• 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.

  PMID: 35420551 BACKGROUND

• Brotman RM, Shardell MD, Gajer P, Fadrosh D, Chang K, Silver MI, Viscidi RP, Burke AE, Ravel J, Gravitt PE. Association between the vaginal microbiota, menopause status, and signs of vulvovaginal atrophy. Menopause. 2014 May;21(5):450-8. doi: 10.1097/GME.0b013e3182a4690b.

  PMID: 24080849 BACKGROUND

• Biehl LM, Farowski F, Hilpert C, Nowag A, Kretzschmar A, Jazmati N, Tsakmaklis A, Wieters I, Khodamoradi Y, Wisplinghoff H, Vehreschild MJGT. Longitudinal variability in the urinary microbiota of healthy premenopausal women and the relation to neighboring microbial communities: A pilot study. PLoS One. 2022 Jan 14;17(1):e0262095. doi: 10.1371/journal.pone.0262095. eCollection 2022.

  PMID: 35030190 BACKGROUND

• Anglim B, Phillips C, Shynlova O, Alarab M. The effect of local estrogen therapy on the urinary microbiome composition of postmenopausal women with and without recurrent urinary tract infections. Int Urogynecol J. 2022 Aug;33(8):2107-2117. doi: 10.1007/s00192-021-04832-9. Epub 2021 May 18.

  PMID: 34003309 BACKGROUND

MeSH Terms

Interventions

Vaginal Creams, Foams, and Jellies

Intervention Hierarchy (Ancestors)

Dosage Forms; Pharmaceutical Preparations; Feminine Hygiene Products; Equipment and Supplies

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD-PhD

Model Details: There are 2 intervention groups and 2 control groups. Control group1 consists of menopause patients without symptoms of GUS and examination findings. Control group 2 consists of menopause patients without symptoms of GUS but have examination findings. Intervention groups are those with GUS symptoms. They were randomly divided in 2 groups: one group had vaginal oestrogen treatment first other group had the treatment after the samples were taken.

Study Record Dates

• First Submitted: October 7, 2024
• First Posted: October 9, 2024
• Study Start: November 10, 2023
• Primary Completion: July 10, 2024
• Study Completion: July 10, 2024
• Last Updated: October 9, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

TU (1)