Please select the eligibility criteria that correspond to the clinical trial below.
Title: The Vaginal Health Trial - Effects of Vaginal Estradiol Tablet and Moisturizing Gel on Postmenopausal Vaginal Symptoms
Brief 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.


Options:
A: Inclusion Criteria:

* Histological confirmation of breast cancer in post menopausal women (age \>=60). Positive hormone receptor status (ER +ve and/or PgR +ve) of primary or metastatic tumour tissue based on local laboratory assessment.
* EITHER locally advanced disease (1 line of chemotherapy allowed only if remain unsuitable for therapy of curative intent) OR Metastatic disease. (1 line of chemotherapy for breast cancer allowed only if subsequent evidence of further progressive disease)
* At least 1 lesion (measurable and/or non-measurable) that can be accurately assessed at baseline and is suitable for repeated assessment.
* Postmenopausal women, fulfilling 1 of:

  * Prior bilateral oophorectomy
  * Age \>60 years
  * Age \< 60 years and amenorrheic for 12+months in the absence of chemotherapy, tamoxifen, toremifene, or ovarian suppression and FSH and oestradiol in the postmenopausal range

Exclusion Criteria:

* Presence of life-threatening metastatic disease
* Any of:

  * Extensive hepatic involvement
  * involving brain or meninges
  * symptomatic pulmonary lymph spread
* Discrete lung metastases are acceptable if respiratory function is not significantly compromised
* Prior systemic therapy for breast cancer other than one line of cytotoxic chemotherapy (the last dose of chemotherapy must have been received more than 28 days prior to randomisation)
* Radiation therapy if not completed within 28 days prior to randomisation (with the exception of radiotherapy given for control of bone pain, started prior to randomisation). Prior hormonal treatment for breast cancer.
* Current or prior malignancy within previous 3 years (other than breast cancer or adequately treated basal cell or squamous cell carcinoma of the skin or in situ carcinoma of the cervix).
B: Inclusion Criteria:

* menses absent for at least 6 months and no more than 36 months
* good general health
* plasma FSH level greater than or equal to 35 mIU/ml
* estradiol levels \< 40 pg/ml
* normal mammogram within 1 year of randomization

Exclusion Criteria:

* use of hormone replacement or supplement within 3 months of randomization
* endometrial thickness \>5 mm by vaginal ultrasound
* in utero exposure to diethylstilbestrol (DES)
* current smoking \> 10 cigarettes/day
* obesity-body mass index \> 35
* history of clinical cardiovascular disease
* history of cerebrovascular disease
* history of thromboembolic disease
* coronary calcium score ≥ 50 units
* dyslipidemia-LDL cholesterol \>190 mg/dl
* hypertriglyceridemia-triglycerides \>400 mg/dl
* lipid lowering medication (statin, fibrate,or \> 500 mg/day of niacin)
* nut allergy (Prometrium includes peanut oil)
* uncontrolled hypertension-systolic BP \>150 and/or diastolic BP \> 95
* hysterectomy
* history of, or prevalent, chronic diseases including any cancer (other than basal cell skin cancers), renal failure, cirrhosis, diabetes mellitus, and endocrinopathies other than adequately treated thyroid disease
* known HIV infection and/or medications for HIV infection
* results of any safety laboratory test chemistries, (TSH, CBC, U/A) more than 20% abnormal
C: 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)
D: Inclusion Criteria:

* Generally healthy
* Postmenopausal
* Hysterectomized or non-hysterectomized
* Moderate or severe vaginal dryness and soreness

Exclusion Criteria:

* Known, suspected, or past history of breast cancer
* Known, suspected, or past history of hormone-dependent tumor
* Genital bleeding of unknown etiology
* Acute thrombophlebitis or thromboembolic disorders or a past history of these conditions, associated with previous estrogen use
* Vaginal infection
* Use of exogenous corticosteroids or sex hormones within 8 weeks of starting active treatment in study
* Use of vaginal, oral or vulvar homeopathic preparations within seven days of starting active treatment in study
* History of treatment with diethylstilbestrol

Answer: C