Vaginal Estrogen Therapy Is Associated With Increased Lactobacillus in the Urine of Postmenopausal Women With Overactive Bladder Symptoms

Abstract

Introduction-Previous work has shown that the vaginal microbiome decreases in Lactobacilluspredominance and becomes more diverse following menopause. It has also been shown that estrogen therapy restores Lactobacillus-dominance in the vagina, and that topical estrogen is associated with OAB symptom improvement. We now know that the bladder contains a unique microbiome, and increased bladder microbiome diversity is associated with OAB. However, there is no understanding of how quickly each pelvic floor microbiome responds to estrogen or if those changes are associated with symptom improvement.Study Design-Analysis of data from post-menopausal participants in two trials (NCT02524769 and NCT02835846) who chose vaginal estrogen as their primary OAB treatment and used 0.5 grams of conjugated estrogen (Premarin Cream, (Pfizer, New York City, NY)) twice weekly for 12 weeks. Baseline and 12-week follow-up data included the OAB-q questionnaire and participants provided catheterized urine, vaginal swabs, perineal swabs, and voided urine. Microbes were detected by an enhanced culture protocol. Linear mixed models were used to estimate microbiome changes over time. Urinary AMP activity was assessed by a bacterial growth inhibition assay and correlated with relative abundance of members of the urobiome.Results-Twelve weeks of estrogen treatment resulted in decreased microbial diversity within the vagina (Shannon, p=0.047; Richness, p=0.043), but not in the other niches. A significant increase in Lactobacillus was detected in the bladder (p=0.037), but not the vagina (p=0.33), perineum (p=0.56), or voided urine (p=0.28). The change in Lactobacillus levels in the bladder was associated with modest changes in urgency incontinence symptoms (p=0.02). The relative abundance of the genus Corynebacterium correlated positively with urinary AMP activity after estrogen treatment. Conclusion-Estrogentherapy may change the microbiome of different pelvic floor niches. The vagina begins to decrease in diversity and the bladder experiences a significant increase in Lactobacillus levels; the latter is correlated with a modest improvement in the symptom severity sub-scale of the OAB-q. CondensationEstrogen therapy for overactive bladder resulted in decreased bladder bacterial diversity and increased bladder Lactobacillus, which were associated with modest changes in urgency incontinence symptoms.

Recurrent urinary tract infection and estrogen shape the taxonomic ecology and functional potential of the postmenopausal urobiome

“…Our analysis of cohort-associated metadata found a strong link between EHT use and the presence of Lactobacillus in the urobiome of non-infected patients. These observations support those made by Thomas-White et al and are of particular interest to research endeavors seeking to identify possible UTI-protective members of the urinary and urogenital tract microbial communities (Thomas-White et al, 2020). Lactobacilli control the local chemical environment of the vagina and are responsible for not only maintaining an acidic pH, but also secrete large amounts of the antimicrobial D (-) lactate isomer (Amabebe and Anumba, 2018).…”

“…In a 2021 report, Anglim et al found no difference in urinary lactobacilli among postmenopausal women with and without rUTI taking vaginal EHT compared to baseline controls (Anglim et al, 2021). However, Thomas-White et al reported a significant enrichment of lactobacilli in the bladders of postmenopausal women with overactive bladder symptoms using vaginal EHT (Thomas-White et al, 2020). These results along with our report suggest nuances in the association between urinary lactobacilli and EHT that merit future mechanistic research.…”

“…While the urobiome has been importantly and robustly characterized using bacterial 16S amplicon sequencing, few WGMS studies have been reported (Ammitzboll et al, 2021;Moustafa et al, 2018;Siddiqui et al, 2011;Thomas-White et al, 2020;Vaughan et al, 2021). This unbiased approach allows for the profiling of prokaryotic, eukaryotic, archaeal, and viral taxa present in the sample.…”

“…We then performed exploratory correlation analysis of creatinine-normalized estrogen metabolite concentrations and the species-level taxonomic profile. Multiple studies have assessed association between urinary and vaginal Lactobacillus abundance and host estrogen status with varying conclusions (Anglim et al, 2021;Thomas-White et al, 2020). However, it remains unknown if urinary Lactobacillus abundance is directly correlated with host systemic or excreted estrogen concentration.…”

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

“…If indeed an underlying dysbiosis of the urinary bladder and vaginal microbiome are believed to correspond with lower urinary tract symptomatology, which has been suggested in previous studies, then one would expect to also see more changes in the bacterial community for more symptomatic women. This was the case in a study by Thomas-White et al 18 of postmenopausal women with overactive bladder symptoms, showing an increase in urinary bladder Lactobacillus after vaginal estrogen supplementation, which correlated to symptom improvement. Another study by Komesu et al 23 did not find overall differences in urinary bladder Lactobacillus predominance in women with and without mixed urinary incontinence, although subgroup analysis suggested that in women younger than 51 years, a decreased Lactobacillus predominance was associated with mixed urinary incontinence.…”