The Impact of Local Estrogen on the Urogenital Microbiome in Genitourinary Syndrome of Menopause: A Randomized-Controlled Trial

Abstract

ImportanceThe postmenopausal urinary bladder microbiome is not well defined.ObjectivesThe aims of this study were to characterize the effect of vaginal estrogen on the vaginal and urinary bladder microbiome in postmenopausal women and describe any clinical associations with the symptoms of genitourinary syndrome of menopause.Study DesignThis was a participant-masked, randomized controlled trial comparing the effect of a 12-week course of an estrogen-containing vaginal ring to a placebo vaginal ring. Standardized evaluations were performed at baseline and 12 weeks. Vaginal samples were obtained for pH, vaginal maturation index, and microbiome analysis. Concomitant catheterized urine samples were obtained for microbiome analysis. 16S ribosomal RNA gene sequencing was performed to characterize the resident microbial communities, with Lactobacillus relative abundance as the primary outcome variable. Genitourinary syndrome of menopause symptoms was measured using validated questionnaires (Pelvic Floor Distress Inventory–Short Form, Female Sexual Function Index, Vulvovaginal Symptoms Questionnaire).ResultsOf the 39 postmenopausal women randomized, baseline characteristics were similar between arms, with a mean age of 62 years and mean vaginal pH of 5.0. Using intention-to-treat analysis, there were no significant changes in vaginal or urinary Lactobacillus relative abundance. Two participants in each arm removed their ring prior to the end of the study. Eighty percent of participants experienced at least 1 bothersome genitourinary syndrome of menopause symptom. Vulvovaginal dryness and urinary frequency were most common at baseline, whereas painful intercourse and urinary urgency were most common at the final visit, none of which were statistically significant.ConclusionsOur study did not show a significant change in the bacterial composition of the vaginal or urinary bladder microbiome after either vaginal ring in this relatively asymptomatic postmenopausal population.

Recurrent urinary tract infection and estrogen shape the taxonomic ecology and function of the postmenopausal urogenital microbiome

“…did not find significant changes in urogenital Lactobacillus enrichment following local EHT. 76 We observed that Lactobacillus -dominated urogenital microbiomes were associated with women using oEHT (n = 6) and pEHT (n = 6). While reports of systemic EHT-associated urogenital Lactobacillus enrichment are few, a 2016 interventional study using oral conjugated estrogens demonstrated a rapid and significant increase in vaginal Lactobacillus spp.…”

“… 82 , 83 , 84 , 85 While the variable association between vEHT and urogenital Lactobacillus abundance is in line with previous observations, the relatively small sample size of this study is a limitation. 36 , 53 , 76 Given the inherent variability in human-derived data, future longitudinal studies with large, controlled cohorts as well as appropriate animal models will be critical to gaining a mechanistic understanding of the relationship between EHT and urogenital microbiome composition.…”

Menopausal Changes in the Microbiome—A Review Focused on the Genitourinary Microbiome

“…Postmenopausal women may undergo local hormone therapy for primary or secondary prevention of urinary tract infections [ 11 , 72 ]. Lillemon et al [ 73 ] investigated the effects of a 12-week estrogen-containing vaginal ring on the bladder microbiome in postmenopausal women and observed no significant changes after treatment. However, other studies found that local vaginal estrogen therapy increased vaginal [ 74 ] and bladder [ 75 ] Lactobacillus counts in menopausal women, and local vaginal estrogen supplementation and Lactobacillus supplements decreased the risk of urinary tract infections among patients with recurrent urinary tract infections [ 74 , 76 , 77 , 78 ].…”

“…Thus, altering the vaginal microbiome with estrogen or Lactobacillus supplementation could be considered as a treatment option for GSM. Lillemon et al [ 73 ] reported that treatment with 12 weeks of vaginal estrogen just changed the main symptoms of GSM from vulvovaginal dryness and urinary frequency to dyspareunia and urgency without significant improvement of GSM symptoms. There was a pilot RCT attempting to improve GSM using the microbiome [ 88 ].…”

Hormone therapy for sexual function in perimenopausal and postmenopausal women: a systematic review and meta-analysis update

“…Among the 20 studies published since December 2012, 14 studies evaluated estrogen therapy. 31,32,34,36,38,39,41,42,[50][51][52][57][58][59][60][61][62] Four studies evaluated estrogen plus progestogen therapy. 33,37,40,49 One study evaluated tibolone.…”