A Phase 3, Randomized, Three-Cycle, Double-Blind, Placebo-Controlled Study to Evaluate Induction of Secretory Conversion of Endometrium and Withdrawal Bleeding for Secondary Amenorrhea

Inclusion Criteria:

- Be female, premenopausal, 18 to 40 years of age (inclusive, at the time of
randomization)

- Have secondary amenorrhea, defined as the absence of menstruation for at least 90 days
prior to Visit 1 (Cycle 1, Day 1).

- Have an intact uterus.

- Be otherwise healthy, as judged by the Investigator physician, based on a medical
evaluation performed during the screening period prior to the initial dose of
Estrace®. The medical evaluation must include:

- a normal or non-clinically significant physical examination, including vital
signs (sitting blood pressure, heart rate, respiratory rate and temperature).
Acceptable sitting systolic blood pressure is <140 mmHg and diastolic blood
pressure is <90 mmHg at screening. A subject may be taking up to two
antihypertensive medications.

- a normal or non-clinically significant pelvic examination performed during
screening.

- a normal or non-clinically significant clinical breast examination performed
during screening. An acceptable breast examination is defined as no masses,
adenopathy, or other findings identified that are suspicious of malignancy.

- a normal or non-clinically significant 12-lead ECG as determined by the Principal
Investigator (PI) or medical Sub-Investigator.

- Have a negative serum pregnancy test at Screening, and be willing to use an acceptable
form of non-hormonal birth control (e.g., barrier method with spermicide) during the
study. (The "rhythm method," withdrawal, or an IUD are NOT acceptable methods.)

Exclusionary:

- Be postmenopausal.

- Be diagnosed with primary amenorrhea.

- Have had bilateral oophorectomy and/or hysterectomy.

- Have a history of thrombosis of deep veins or arteries or a thromboembolic disorder.

- Have a history of coronary artery or cerebrovascular disease (e.g., myocardial
infarction, stroke, TIA).

- Have a history of liver or kidney dysfunction/disorder (e.g., hepatitis C or chronic
renal failure).

- Have a history of gallbladder dysfunction/disorders (e.g., cholangitis,
cholecystitis), unless gallbladder has been removed.

- Have a history of diabetes, thyroid disease or any other endocrine disease. (Subjects
with diet-controlled diabetes or controlled hypothyroid disease at screening are not
excluded.)

- Have a history of undiagnosed vaginal bleeding.

- Have any history of endometrial hyperplasia, uterine/endometrial, breast or ovarian
cancer.

- Have any history of malignancy within the last 5 years, with the exception of basal
cell (excluded if within one year) or squamous cell (excluded if within one year)
carcinoma of the skin.

- Have a history of any other cardiovascular, hepatic, renal, pulmonary, hematologic,
gastrointestinal, endocrine, immunologic, dermatologic, neurologic, psychological, or
musculoskeletal disease or disorder that is clinically significant in the opinion of
the Principal Investigator or medical Sub-Investigator.

- Have used injectable or implantable estrogen, progestin/progesterone, testosterone or
androgens within the last 6 months prior to Visit 1 or plan to use them during the
study.

- Have used any of the following hormonal products within the last 90 days prior to
Visit 1 or plan to use them during the study:

- Vaginal nonsystemic hormonal products (rings, creams, gels) or vaginal systemic
hormonal products (e.g., FemRing).

- Transdermal estrogen alone or combination estrogen and progestin/progesterone
products.

- Oral hormonal birth control or oral estrogen and/or progestin/progesterone
therapy.

- Percutaneous estrogen lotions/gels.

- Have used oral, topical, vaginal, or patch testosterone or androgen therapy within the
last 8 weeks (56 days) prior to Visit 1 or plan to use them during the study.

- Have used injectable corticosteroids within the last 42 days prior to Visit 1 or plan
to use them during the study.

- Have used an IUD (either hormonal or non-hormonal) within the previous 90 days prior
to Visit 1 or plan to use one during the study.

- Have used, within 28 days prior to the initial dose of Estrace® at Baseline Visit 1,
or plan to use during the study, any prescription or over-the-counter (OTC)
medications (including herbal products, such as St. John's Wort) that would be
expected to alter progesterone activity. (For additional details, see Concomitant and
Prohibited Medications, Section 4.3.

- Have participated in another clinical trial within 30 days prior to screening, have
received an investigational drug within the 90 days prior to the initial dose of
Estrace®, or be likely to participate in a clinical trial or receive another
investigational medication during the study.

- Have contraindication to any planned study assessments (e.g., endometrial biopsy).