Vaginal and Urinary Microbiome Trial

Menopause Clinical Trial

Official title:

The Effects of Vaginal Estrogen and a Nonhormonal Alternative on the Vaginal and Urinary Microbiome in Women With Genitourinary Syndrome of Menopause: A Randomized Controlled Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02869165
• Other study ID #: 16.0428
• Status: Completed
• Phase: Phase 4
• Start date: January 2017
• Est. completion date: December 31, 2019

Study information

• Verified date: May 2021
• Source: University of Louisville
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

A randomized controlled trial looking at the effects of vaginal estrogen and a nonhormonal alternative on the vaginal and urinary microbiome in women with genitourinary syndrome of menopause.

Description:

This is a study is looking at the effects of vaginal estrogen and a nonhormonal alternative on the vaginal and urinary microbiome in women with genitourinary syndrome of menopause. The primary objective is to describe the bacterial communities associated in the vagina and urine of postmenopausal women receiving treatment for genitourinary syndrome of menopause with conjugated equine estrogen topical cream (Premarin®) and a nonhormonal alternative (apricot kernel oil). The participants will be randomized to either conjugated equine estrogen topical vaginal cream or apricot kernel oil. They will be given validated questionnaires to assess their urinary and vaginal symptoms, sexual function, quality of life, and impressions of severity and improvement.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 110
• Est. completion date: December 31, 2019
• Est. primary completion date: June 30, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Age 18-years old

• Women who qualify for vaginal estrogen

• Suitability for follow-up

• Hormonally post-menopausal status: Bilateral past ovarian removal, =1 year since last menses if uterus in place, OR hysterectomized woman with =1 ovary in place AND >1 year of menopausal symptoms or laboratory confirmation of menopausal hormonal status (such as serum follicle stimulation hormone >25 IU/mL)

• GSM symptoms (including, but not limited to genital symptoms of dryness, burning, itching, and irritation; sexual symptoms of lack of lubrication, discomfort or pain, and impaired sexual function; and urinary symptoms of urgency, frequency, dysuria and recurrent (UTIs)

Exclusion Criteria:

• Age < 18-years old

• Known allergic reaction or other adverse reactions to Premarin® or any of its components or apricot kernel oil

• Nut allergy

• Inability to use or place vaginal therapy due to altered mental status or anatomical reasons

• Already using vaginal estrogen or apricot kernel oil in the past two weeks

• Known active vaginal infection (symptomatic and/or untreated) or completion of treatment for bacterial vaginosis or cervical/vaginal infection within one week of recruitment

• History of recurrent or chronic bacterial vaginosis with > 2 episodes per year or symptoms reported for > 6 months out of the last year.

• History of active vaginal ulcerative disease (active ulcers from atrophy, herpes symptoms at recruitment or herpes with >2 outbreaks per year or last outbreak <1month ago, or vaginal laceration.

• Chronic antibiotic or probiotic use for indications not listed.

• Pelvic organ prolapse beyond the hymenal ring

• Using a vaginal pessary or indwelling urinary catheter

• Evidence of active urinary tract infection by history and symptoms, urine dipstick, or urine culture on day of presentation or within last 2 weeks (defined as = 100,000 colonies same pathologic bacteria on clean catch or 10,000 colonies on straight catheter specimen)

• Recurrent urinary tract infection 3 episodes with the last year or 2 episodes within the last 6 months.

• History of venous or arterial thromboembolism or genetic predisposition to thromboembolism.

• Ovarian cancer and estrogen responsive cancer including endometrial or breast or breast cancer history of unknown hormonal status

• Vaginal mesh erosion, sutures visible in the vagina or granulation tissue

• Uncorrected vesicovaginal or rectovaginal fistula

• Severe fecal or anal incontinence

• Active vulvar dermatoses (lichen sclerosis, Behcet's disease, vulvar eczema) and on chronic topical steroids.

• Subjects with absolute contraindications to estrogen, such as diabetes mellitus with end-organ damage and vascular disease, impaired liver function or a hepatic hemangioma, chronic renal disease, migraine with aura, systemic lupus erythematosus with prior thrombosis or vascular damage or other end-organ damage

• Patients < 6 weeks postop

• Inability to speak or read English

Related Conditions & MeSH terms

• Atrophic Vaginitis
• Menopause
• Recurrent Urinary Tract Infections
• Urinary Tract Infections
• Vaginitis

Intervention

Drug:
• Conjugated equine estrogen topical cream
Comparison of the bacterial communities in the vagina and urine of postmenopausal women who use Premarin vaginal cream versus apricot kernel oil and to themselves before and after use.
• Apricot kernel oil
Comparison of the bacterial communities in the vagina and urine of postmenopausal women who use Premarin vaginal cream versus apricot kernel oil and to themselves before and after use.

Locations

Country	Name	City	State
United States	Health Care Outpatient Center and Springs Medical Center	Louisville	Kentucky

Sponsors (1)

Lead Sponsor	Collaborator
University of Louisville

Country where clinical trial is conducted

United States, 

References & Publications (21)

Bygdeman M, Swahn ML. Replens versus dienoestrol cream in the symptomatic treatment of vaginal atrophy in postmenopausal women. Maturitas. 1996 Apr;23(3):259-63. — View Citation

Coyne KS, Margolis MK, Thompson C, Kopp Z. Psychometric equivalence of the OAB-q in Danish, German, Polish, Swedish, and Turkish. Value Health. 2008 Dec;11(7):1096-101. doi: 10.1111/j.1524-4733.2008.00346.x. Epub 2008 May 16. — View Citation

Danforth KN, Townsend MK, Lifford K, Curhan GC, Resnick NM, Grodstein F. Risk factors for urinary incontinence among middle-aged women. Am J Obstet Gynecol. 2006 Feb;194(2):339-45. — View Citation

Erekson EA, Yip SO, Wedderburn TS, Martin DK, Li FY, Choi JN, Kenton KS, Fried TR. The Vulvovaginal Symptoms Questionnaire: a questionnaire for measuring vulvovaginal symptoms in postmenopausal women. Menopause. 2013 Sep;20(9):973-9. doi: 10.1097/GME.0b01 — View Citation

Freedman M, Kaunitz AM, Reape KZ, Hait H, Shu H. Twice-weekly synthetic conjugated estrogens vaginal cream for the treatment of vaginal atrophy. Menopause. 2009 Jul-Aug;16(4):735-41. doi: 10.1097/gme.0b013e318199e734. — View Citation

Hopwood P, Fletcher I, Lee A, Al Ghazal S. A body image scale for use with cancer patients. Eur J Cancer. 2001 Jan;37(2):189-97. — View Citation

Hummelen R, Macklaim JM, Bisanz JE, Hammond JA, McMillan A, Vongsa R, Koenig D, Gloor GB, Reid G. Vaginal microbiome and epithelial gene array in post-menopausal women with moderate to severe dryness. PLoS One. 2011;6(11):e26602. doi: 10.1371/journal.pone — View Citation

Jelovsek JE, Barber MD. Women seeking treatment for advanced pelvic organ prolapse have decreased body image and quality of life. Am J Obstet Gynecol. 2006 May;194(5):1455-61. — View Citation

Lamont RF, Sobel JD, Akins RA, Hassan SS, Chaiworapongsa T, Kusanovic JP, Romero R. The vaginal microbiome: new information about genital tract flora using molecular based techniques. BJOG. 2011 Apr;118(5):533-49. doi: 10.1111/j.1471-0528.2010.02840.x. Ep — View Citation

Levine KB, Williams RE, Hartmann KE. Vulvovaginal atrophy is strongly associated with female sexual dysfunction among sexually active postmenopausal women. Menopause. 2008 Jul-Aug;15(4 Pt 1):661-6. doi: 10.1097/gme.0b013e31815a5168. — View Citation

Management of symptomatic vulvovaginal atrophy: 2013 position statement of The North American Menopause Society. Menopause. 2013 Sep;20(9):888-902; quiz 903-4. doi: 10.1097/GME.0b013e3182a122c2. — View Citation

Martin DH. The microbiota of the vagina and its influence on women's health and disease. Am J Med Sci. 2012 Jan;343(1):2-9. doi: 10.1097/MAJ.0b013e31823ea228. Review. — View Citation

Nachtigall LE. Comparative study: Replens versus local estrogen in menopausal women. Fertil Steril. 1994 Jan;61(1):178-80. — View Citation

Parish SJ, Nappi RE, Krychman ML, Kellogg-Spadt S, Simon JA, Goldstein JA, Kingsberg SA. Impact of vulvovaginal health on postmenopausal women: a review of surveys on symptoms of vulvovaginal atrophy. Int J Womens Health. 2013 Jul 29;5:437-47. doi: 10.214 — View Citation

Rahn DD, Carberry C, Sanses TV, Mamik MM, Ward RM, Meriwether KV, Olivera CK, Abed H, Balk EM, Murphy M; Society of Gynecologic Surgeons Systematic Review Group. Vaginal estrogen for genitourinary syndrome of menopause: a systematic review. Obstet Gynecol — View Citation

Rahn DD, Ward RM, Sanses TV, Carberry C, Mamik MM, Meriwether KV, Olivera CK, Abed H, Balk EM, Murphy M; Society of Gynecologic Surgeons Systematic Review Group. Vaginal estrogen use in postmenopausal women with pelvic floor disorders: systematic review a — View Citation

Rogers RG, Rockwood TH, Constantine ML, Thakar R, Kammerer-Doak DN, Pauls RN, Parekh M, Ridgeway B, Jha S, Pitkin J, Reid F, Sutherland SE, Lukacz ES, Domoney C, Sand P, Davila GW, Espuna Pons ME. A new measure of sexual function in women with pelvic floo — View Citation

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. — View Citation

Suckling J, Lethaby A, Kennedy R. Local oestrogen for vaginal atrophy in postmenopausal women. Cochrane Database Syst Rev. 2006 Oct 18;(4):CD001500. Review. Update in: Cochrane Database Syst Rev. 2016;8:CD001500. — View Citation

Ware J Jr, Kosinski M, Keller SD. A 12-Item Short-Form Health Survey: construction of scales and preliminary tests of reliability and validity. Med Care. 1996 Mar;34(3):220-33. — View Citation

Yalcin I, Bump RC. Validation of two global impression questionnaires for incontinence. Am J Obstet Gynecol. 2003 Jul;189(1):98-101. — View Citation

* Note: There are 21 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Vaginal and urinary predominance of anaerobic/fastidious taxonomy of micro-organisms on genomic, microbial DNA analysis of vaginal and urinary specimens.	Predominance (greater than 50%) in vaginal and urinary specimen of anaerobic and/or fastidious organisms in the study population compared between conjugated equine estrogen cream (Premarin) and apricot kernel oil. The primary analysis will compare the prevalence of genomic taxonomic anaerobic and/or fastidious organism predominance (>50%) between the estrogen group and the non-estrogen alternative group.	3 months
Secondary	Change in vaginal symptom questionnaire (VSQ)	Change in vaginal symptoms as assessed by vulvovaginal symptom questionnaire (VSQ) at baseline and after treatment.	3 months
Secondary	Vaginal and urinary predominance of anaerobic/fastidious taxonomy of micro-organisms on genomic, microbial DNA analysis of vaginal and urinary specimens.	Predominance (greater than 50%) in vaginal and urinary specimen of anaerobic and/or fastidious organisms in the study population compared between the conjugated equine estrogen cream (Premarin) and apricot kernel oil. The primary analysis will compare the prevalence of genomic taxonomic anaerobic and/or fastidious organism predominance (>50%) between the baseline patients and the patients at 3 months and compare the change in prevalence in this taxonomic predominance between the two study groups.	3 months

External Links

•   Age and sex composition: 2010 Census Briefs
•   Organization for Economic Cooperation and Development. Health at a glance 2013: OECD indicators.