The Vaginal Health Trial
Condition: Atrophy of Vagina; Menopause; Dyspareunia (Female)
MeSH terms: Dyspareunia
Intervention: Vagifem; Replens; Placebo tablet; Placebo gel
Intervention description: One tablet is to be inserted vaginally daily for 2 weeks, then 2 days/week for the remaining 10 weeks of the study.; 2.5 gm to be applied vaginally every 3 days over 12 weeks.; Dispensed in visually identical bottle and tablet form to Vagifem.; Dispensed in visually identical tube and gel form to Replens.
Intervention MeSH terms: Estradiol
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 302.0
Sex: Female
Minimum age: 45 Years
Maximum age: 70 Years
Healthy volunteers: No

Summary:

      This is a new application from the Menopause Strategies: Finding Lasting Answers for Symptoms
      and Health (MsFLASH) Clinical Trials network. Here we propose to conduct a large multicenter
      trial comparing two common treatments, a vaginal hormone tablet and an over-the-counter gel,
      with placebo to evaluate their effects on bothersome vaginal symptoms and sexual function,
      and to create a biorepository of specimens for future translational, mechanistic research on
      the etiology of vaginal symptoms.
    

Eligibility criteria:

        Inclusion Criteria

          -  Females aged 45-70 years

          -  2 or more years since last natural menstrual period, or surgical menopause (bilateral
             oophorectomy)

          -  At least 1 vaginal symptom (inside or outside the vagina) reported from the following
             list, experienced in the past 30 days which is moderate or severe:

               -  Dryness at least once a week

               -  Itching at least once a week

               -  Irritation at least once a week

               -  Soreness/Pain at least once a week

               -  Pain associated with sexual activity at least once

          -  Signed informed consent

        Exclusion Criteria

          -  Current unexplained abnormal genital bleeding (or any unevaluated bleeding since
             menopause)

          -  Currently pregnant, attempting pregnancy or breast feeding

          -  Current acute vaginal infection (as indicated by wet mount at V1)

          -  Pelvic or vaginal surgery in prior 60 days

          -  Antibiotic use in the past 30 days

          -  Women under age 55 with endometrial ablation

          -  Women under age 55 with hysterectomy and at least one ovary

          -  Current cancer treatment (exception basal or squamous skin cell cancers)

          -  Current or past thromboembolic disease (pulmonary embolus or deep vein thrombosis, not
             including thrombophlebitis), myocardial infarction or stroke

          -  Current severe liver disease

          -  Current or past breast or endometrial cancer or pre-cancer

          -  Blood clotting disorder (e.g., Factor V Leiden, prothrombin mutation, protein C,
             protein or antithrombin deficiency)

          -  Porphyria

          -  Current or past lichen sclerosus or lichen planus

          -  History of adverse reaction to vaginal estrogen or Replens

          -  Use of any systemic reproductive hormones (hormonal contraception, postmenopausal
             hormone therapies, SERMS) in the past 2 months

          -  Use of hormonal contraception in the past year

          -  Use of any type of vaginal estrogen product (however interested women will be allowed
             to join the study if they abstain from use during the month preceding enrollment)

          -  Use of any type of vaginal moisturizer, douche, vaginal prebiotic or probiotic, or
             soap in the vagina in the past month (however interested women will be allowed to join
             the study if they abstain from use during the month preceding enrollment)

          -  Unwilling to abstain from use of any non-study vaginal moisturizer, vaginal estrogen,
             douche, or soap in the vagina throughout the trial

          -  Unable to follow instructions, complete questionnaires, or physically unable to place
             product in the vagina

          -  Current participation in another drug trial or intervention study

          -  Chronic vulvo-vaginal symptoms in the 5 years before menopause (defined as a vaginal
             or vulvar condition requiring more than 4 visits to a health care provider in a given
             year)