Study to Evaluate the Equivalence of Estradiol Vaginal Cream to Reference Standard in the Treatment of Vaginal Atrophy

Inclusion Criteria

• Signed IRB-approved informed consent form that meets all criteria of current FDA regulations.
• Postmenopausal females aged 30-75 years inclusive. Postmenopausal is defined as follows:
• At least 6 months of spontaneous amenorrhea.
• At least 6 weeks post-surgical bilateral oophorectomy, with or without hysterectomy.
• Hysterectomy without oophorectomy if of age that the Investigator believes would have naturally reached 12 months of spontaneous amenorrhea if uterus had remained intact.
• Patients with a serum Follicle Stimulating Hormone (FSH) level of ≥ 40 mIU/mL at Screening.
• Have ≤ 5% superficial cells on vaginal smear cytology.
• Have a vaginal pH > 5.0.
• At least one of the following patient self-assessed moderate to severe symptoms of VVA from the following list that is identified by the patient as being the most bothersome to her:
• Vaginal Dryness
• Vaginal and/or Vulvar Irritation/Itching
• Dysuria
• Vaginal Pain associated with sexual activity
• Vaginal Bleeding associated with sexual activity (presence or absence)
• Provided that patient is currently sexually active and plans to remain so throughout the study.
• Have "Normal" Screening mammogram completed within 9 months before Screening in all patients > 40 years old, with no findings that, in the opinion of the Investigator, would indicate any suspicion of breast malignancy.
• Normal clinical breast examination at Screening.
• Patients with an intact uterus (including patients who underwent a partial hysterectomy) must have a documented papanicolaou (PAP) smear conducted within the previous 12 months with no findings that the Investigator believes would contraindicate the use of topical vaginal estradiol.
• Patients with an intact uterus should have vaginal ultrasonography results within 3 months before Screening to confirm an inactive endometrial lining, defined as endometrial thickness 150 mmHg and/or diastolic pressure > 90 mmHg.
• Any patient with past or current undiagnosed vaginal bleeding or significant risk factors for endometrial cancer.
• Any history of estrogen-dependent neoplasia (e.g., endometrial cancer).
• Patients with known, suspected or current history of hormone dependent tumor.
• History of acute thrombophlebitis or thromboembolic disorder.
• Any prescription treatment for vaginal dryness/irritation within 14 days before Screening or any over-the-counter or natural remedies within 7 days before Screening.
• Any prescription treatment for bacterial or yeast infections within 30 days before Screening.
• Fasting triglyceride levels > 350 mg/dL.
• History of radiation therapy or recent (within previous 6 weeks) surgical therapy to the vaginal or cervical areas.
• Any known or suspected allergies that, in the Investigator's opinion, would compromise the safety of the patient.
• Patients who have used vaginal hormonal products (rings, creams, gels) within the 7 days before Screening.
• Patients who have used transdermal estrogen and/or progestin therapy within the 28 days before Screening.
• Patients who have used oral estrogen and/or progestin therapy or intrauterine progestin therapy within the 56 days before Screening.
• Patients who have used progestin implants or estrogen alone injectable drug therapy within the 3 month before Screening.
• Patients who have used estrogen pellet therapy or progestin injectable drug therapy within 6 months before Screening.
• History of significant alcohol abuse within 1 year prior to Screening or regular use of alcohol within 6 months before Screening (more than 14 units of alcohol per week [1 unit = 150 mL of wine, 360 mL of beer, or 45 mL of 40% alcohol]).
• History of significant drug abuse within 1 year prior to Screening, use of soft drugs (such as marijuana) within 3 months before Screening, or hard drugs (such as cocaine, phencyclidine [PCP], crack, opioid derivatives including heroin, and amphetamine derivatives) within 1 year before