Estrogen and the Urogenital Microbiome in GSM
Condition: Menopause
Study type: Interventional
Phase: Phase 4

Summary: 
      This is a study of how local estrogen treatment affects the microbiome of the vagina and
      bladder in postmenopausal women experiencing symptoms as part of "Genitourinary Syndrome of
      Menopause." The goal is to understand more about the underlying microbial changes occurring
      in menopause and whether these are reversible with estrogen.
    

Detailed description: 
      Women who have undergone menopause almost ubiquitously experience pelvic complaints at some
      point in the postmenopausal period. This is most commonly vaginal dryness and discomfort
      during sexual intercourse. From previous studies, we know that as estrogen levels decrease in
      menopause, changes occur in the local urogenital tract that include thinning of the vaginal
      epithelium, an increase in pH and an alteration of the composition of the local bacterial
      community, including a decrease in the typically predominant species of bacteria
      lactobacilli. In conjunction with declining estrogen levels, a subset of postmenopausal women
      experience bothersome lower urinary tract symptoms such as burning with urination, urinary
      urgency, incontinence and recurrent urinary tract infections. These symptoms are commonly
      underreported, under-treated, and have been associated with reduced quality of life and
      decreased productivity in menopause. "Genitourinary Syndrome of Menopause" (GSM) is a term
      adapted to be more inclusive of these lower urinary tract symptoms in an effort to reduce
      delays in evaluation and treatment. It remains controversial whether these symptoms relate
      directly to estrogen deprivation or are part of the "natural" aging process. Mainstay therapy
      includes vaginal lubricants and local estrogen therapy. Though treatment with local estrogen
      improves both vaginal dryness as well as urinary symptoms, the mechanism is not well
      understood.

      Additionally, there is a subset of women who do not respond to estrogen treatment or have
      contraindications to estrogen use. Recent research efforts have been exploring the potential
      role that the microbiome may play in female pelvic discomfort and dysfunction. Unlike the
      vagina, the bladder has historically been considered to be a sterile environment, with the
      presence of bacteria implying infection. However, recent research has helped to elucidate
      that, similar to the skin, vagina and gastrointestinal tract, a resident microbial community
      or "microbiome" exists within the female bladder. Disturbances in the urinary microbial
      community have been correlated with conditions such as painful bladder syndrome, overactive
      bladder and urge urinary incontinence. These conditions have considerable symptom overlap
      with those seen in postmenopausal women who are experiencing GSM and may be considered to be
      on the same continuum.

      Though microbiome research over the last decade has accelerated our understanding of the role
      that organisms play in health and disease, the urinary microbiome remains poorly defined.
      Data from ongoing research suggests that the urinary microbiome of pre- and postmenopausal
      women differ, which would suggest that hormone status may play a role in maintaining the
      microbial milieu. This research has helped us to better understand how the urinary microbiome
      varies under normal conditions. In order to better understand the role that estrogen plays in
      maintaining the bladder and vaginal flora, this study aims to characterize the effect of
      local estrogen on the urinary and vaginal microbiomes (together termed the "urogenital
      microbiome") in postmenopausal women.
    

Intervention name(s): Estradiol vaginal ring; Placebo vaginal ring
Intervention type(s): Drug; Other
Intervention description(s): Estradiol 2mg vaginal ring; Silicone vaginal ring without any active estradiol
Intervention MeSH terms: Estradiol
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Participant)
Primary purpose: Basic Science
Keywords: Menopause; Vaginal dryness; Vaginal atrophy; Postmenopause; Estrogen; Urinary microbiome; Estradiol vaginal ring; Genitourinary Syndrome of Menopause; Vaginal microbiome