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

Systemic (oral/transdermal patch) estrogen therapies have been shown to effectively treat
symptoms of atrophic vaginitis, but bear undesirable side effects including increased risk of
heart attacks, stroke, endometrial cancer and breast cancer. Topical therapies (creams,
transvaginal delivery systems) provide low doses of estrogen to the vaginal mucosa to provide
local relief for the symptoms of atrophic vaginitis, while reducing the unwanted side effects
associated with systemic delivery systems. Low dose, topical estrogen therapy is considered
most appropriate and convenient for the treatment of vaginal symptoms associated with
menopause, particularly when other symptoms including bone loss or vasomotor dysfunction do
not need to be targeted.

Inclusion Criteria:

- Signed Informed Consent Form (ICF) that meets all criteria of current 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.

- Hysterectomy without oophorectomy if of age that Investigator believes would have
naturally reached 12 months of spontaneous amenorrhea.

- Vaginal pH > 5.0.

- At least one of the following patient self-assessed moderate to severe symptoms of
vulvar and vaginal atrophy (VVA) from the following list that is identified by the
patient as being most bothersome to her:

1. Vaginal Dryness

2. Vaginal and/or Vulvar Irritation/Itching

3. Dysuria

4. Vaginal Pain associated with sexual activity*

5. Vaginal Bleeding associated with sexual activity* *provided that patient is
currently sexually active and plans to remain so throughout study.

- "Normal" Screening mammogram completed within 9 months prior to Screening in all
patients > 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.

- Patients with an intact uterus should have vaginal ultrasonography results to confirm
an inactive endometrial lining, defined as endometrial thickness less than 4 mm.

Exclusion Criteria:

1. Females younger than 30 years of age or older than 75 years of age.

2. Patients with a Serum FSH level of ≤ 40 mIU/mL at Screening.

3. Greater than 5% superficial cells on vaginal cytology.

4. Vaginal pH ≤ 5.

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 patient at
undue risk by participation or could jeopardize the integrity of the study
evaluations.

6. Patients with an intact uterus should have vaginal ultrasonography results to confirm
an inactive endometrial lining. Patients with an endometrial thickness equal to or
greater than 4 mm should be excluded.

7. Documented PAP smear conducted within the previous 12 months with findings that the
Investigator believes would contraindicate the use of topical vaginal estradiol.

8. Patients with known concurrent vaginal infections including but not limited to:

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

9. Patients with active vaginal herpes simplex infection or have had an outbreak within
30 days of the first dosing day.

10. Patients with known, suspected or current history of carcinoma of the breast. All
patients over the age of 40 must have had a mammogram performed within 9 months of the
study start and all patients will have a physical breast exam performed at Screening.

11. Patients with known, suspected or current history of hormone dependent tumor.

12. Patients with baseline systolic blood pressure of > 150 mmHg and/or diastolic pressure
> 90 mmHg.

13. Any patient with undiagnosed vaginal bleeding or significant risk factors for
endometrial cancer.

14. Any history of estrogen-dependent neoplasia (e.g., endometrial cancer).

15. History of acute thrombophlebitis or thromboembolic disorder.

16. Any current or recent (within the previous 6 months) genital bleeding of unknown
etiology.

17. 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 days of Screening.

18. Patients whose fasting triglyceride levels are greater than 350 mg/dL.

19. Any patient with a history of radiation therapy or recent (within previous 6 weeks)
surgical therapy to the vaginal or cervical areas.

20. Any known or suspected allergies that in the Investigator's opinion would compromise
the safety of the patient.

21. Patients who have used vaginal hormonal products (rings, creams, gels) within the 28
days prior to Screening.

22. Any patient who has used transdermal estrogen and/or progestin therapy within the 28
days prior to Screening.

23. Patients who have used oral estrogen and/ or progestin therapy or intrauterine
progestin therapy within the 56 days prior to Screening.

24. Patients who have used progestin implants or estrogen alone injectable drug therapy
within the 3 months before Screening.

25. Patients who have used estrogen pellet therapy or progestin injectable drug therapy
within the 6 months before Screening.

26. Patients who, in the opinion of the Investigator, would be non-compliant with the
requirements of the study protocol.

27. Patients who are unable or unwilling to give informed consent.

28. Receipt of any drug as part of a research study within 30 days prior to Screening.

29. Patients who have participated in this study previously.