The Estrogen Impact on Overactive Bladder Syndrome: Female Pelvic Floor Microbiomes and Antimicrobial Peptides

Overactive bladder (OAB) syndrome is characterized by the symptom complex of urinary urgency,
usually with associated frequency and nocturia, with or without urgency urinary incontinence
in the absence of infection or other pathology. Vaginal estrogen, a well-documented treatment
for OAB in hypoestrogenic women, has been shown to improve symptoms of frequency, urgency and
urgency urinary incontinence (UUI). Several theories have been proposed to explain the
mechanism underlying estrogen's effect on lower urinary tract symptoms (LUTS). Investigators
propose that estrogen treatment influences bacterial communities (microbiomes) in the vagina
and bladder and alters urothelial and vaginal (AMPs); thereby improving OAB symptoms in
hypoestrogenic women.

Long-standing medical dogma has been replaced by clear evidence that a female urinary
microbiome (FUM) exists.This suggests that the FUM is a factor in lower urinary tract
symptoms (LUTS) and that FUM diversity contributes to LUTS and treatment response, like the
vaginal microbiome and its contribution to vaginal symptoms.

In hypoestrogenic women, the vaginal microbiome shifts from low diversity communities,
commonly dominated by Lactobacillus, to more diverse communities dominated by anaerobes; this
change can be reversed with estrogen treatment. Since the FUM of women with OAB includes
bacteria similar to those of the vaginal microbiome (e.g. Lactobacillus, Gardnerella, and
diverse anaerobes), investigators reason the FUM would respond similarly to estrogen and
become less diverse. While almost nothing is known about urinary/vaginal microbiome
interplay, even less is known about immune response modulation in the bladder and vagina.
However, estrogen reduces the subsequent urinary tract infection (UTI) rate in hypoestrogenic
women affected by recurrent UTI, and estrogen induces urothelial antimicrobial peptide (AMP)
expression. Since AMPs exhibit microbicidal activity, stimulate inflammation, and facilitate
epithelial barrier homeostasis, estrogen may work through AMPs as mediators to optimize
microbial equilibrium.

Inclusion Criteria:

- Clinical diagnosis of Overactive bladder

- Clinical diagnosis of Postmenopausal:

- English language skills sufficient to complete questionnaires

- Clinical indication for vaginal estrogen use

- Not currently receiving vaginal estrogen therapy

Exclusion Criteria:

- Currently on systemic hormone replacement therapy (HRT) Have been on HRT within the
past three months

- Clinical diagnosis of estrogen dependent malignancies

- Allergy to local estrogen therapy

- Insufficient language skills to complete study questionnaires

- Women with active, urinary tract infection

- Received antibiotics within the past two weeks

- Clinical diagnosis of stage 3 or 4 pelvic organ prolapse

- Patient unwilling to use vaginal estrogen preparation

- Currently on anticholinergic medication Have received anticholinergic medication
within the past three months

- Previously failed two medications for treatment of OAB Previously received
intra-vesicle botulinum toxin injections Previously had posterior tibial nerve
stimulation Previously had implantation of sacral neuromodulator

- Patients wishing to start anticholinergic medication at the initial encounter

- Undiagnosed abnormal genital bleeding

- Clinical diagnosis of deep vein thrombosis (DVT) Clinical diagnosis of pulmonary
embolism (PE)

- Clinical diagnosis of arterial thromboembolic disease

- Clinical diagnosis of liver dysfunction or disease

- Clinical diagnosis of protein C, protein S or antithrombin or deficiency other known
thrombophilic disorders