Study to Evaluate Equivalence of Estradiol Vaginal Cream 0.01% to Estrace® Cream 0.01% in Atrophic Vaginitis

Inclusion Criteria

• Signed Informed Consent Form (ICF) that meets all criteria of current Food and Drug Administration (FDA) regulations.
• Females aged 30-75 years inclusive who are postmenopausal, defined as follows:
• At least 12 months of spontaneous amenorrhea or 6 months of spontaneous amenorrhea with serum follicle-stimulating hormone (FSH) level of >40 milli-international units per milliliter (mIU/mL); at least 6 weeks post-surgical bilateral oophorectomy, with or without hysterectomy; or hysterectomy without oophorectomy if of age that the Investigator believes would have been naturally reached 12 months of spontaneous amenorrhea.
• Vaginal pH >5.0.
• At least 1 of the following participant self-assessed moderate to severe symptoms of vulvar and vaginal atrophy (VVA) from the following list that is identified by the participant as being most bothersome to her:
• Vaginal Dryness
• Vaginal and/or vulvar irritation/itching
• Dysuria
• Vaginal pain or bleeding associated with sexual activity, provided that participant is currently sexually active and plans to remain so throughout study.
• "Normal" Screening mammogram completed within 9 months prior to Screening in all participants >40 years old.
• Normal clinical breast examination at the Screening Visit.
• 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.
• Participants with an intact uterus should have vaginal ultrasonography results to confirm an inactive endometrial lining, defined as endometrial thickness less than 4 millimeters (mm).

Exclusion Criteria

• Females younger than 30 years of age or older than 75 years of age.
• Participants with a Serum follicle-stimulating hormone (FSH) level of ≤40 mIU/mL at Screening.
• Greater than 5% superficial cells on vaginal cytology.
• Vaginal pH ≤5.
• Significant history or current evidence of chronic infectious disease, system disorder, organ disorder (including significant liver/kidney impairment) or other medical condition that in the Investigator's opinion would place the study participant at undue risk by participation or could jeopardize the integrity of the study evaluations.
• Participants with an intact uterus should have vaginal ultrasonography results to confirm an inactive endometrial lining. Participants with an endometrial thickness equal to or greater than 4 mm.
• Documented PAP smear conducted within the previous 12 months with findings that the Investigator believes would contraindicate the use of topical vaginal estradiol.
• Participants with known concurrent vaginal infections including but not limited to:

Candida albicans, Trichomonas vaginalis, Chlamydia trachomatis, Neisseria gonorrhea, or Gardnerella vaginalis.

• Participants with active vaginal herpes simplex infection or have had an outbreak within 30 days of the first dosing day.
• Participants with known, suspected, or current history of carcinoma of the breast. All participants over the age of 40 must have had a mammogram performed within 9 months of the study start and all participants will have a physical breast exam performed at Screening.
• Participants with known, suspected or current history of hormone dependent tumor.
• Participants with baseline systolic blood pressure of >150 millimetres of mercury (mmHg) and/or diastolic pressure >90 mmHg.
• Any participant with undiagnosed vaginal bleeding or significant risk factors for endometrial cancer.
• Any history of estrogen-dependent neoplasia (for example, endometrial cancer).
• History of acute thrombophlebitis or thromboembolic disorder.
• Any current or recent (within the previous 6 months) genital bleeding of unknown etiology.
• Any prescription treatment or over-the-counter (OTC) or natural remedies for vaginal dryness/irritation within 28 days of Screening. Products used for lubrication during sexual intercourse within 7 d