Inclusion Criteria:

- healthy postmenopausal women (ages 50 to 80 y), wherein menopause is defined by the
absence of spontaneous menses for 1 y and a serum concentration of FSH > 30 IU/L and
of (ultrasensitive) estradiol < 20 pg/mL and verified by medical history and
screening blood work;

- normal hemoglobin of >11.0 g/dL in women (a ferritin level will be drawn, and must be
normal, if Hgb is 11.0 - 11.5) , Platelets greater than 200 x 109/L, AST 8-48 U/L.

- Subjects (age 50 and above) will have a screening baseline ECG if not on record from
the past year.

Exclusion Criteria:

- exposure to psychotropic or neuroactive drug within five biological half- lives;

- undesirability, disinclination or ill advisability of withholding estrogen
supplements (e.g. under treatment for symptomatic hot flushes; primary physician
recommendation);

- BMI < 19 or > 35

- drug or alcohol abuse; psychosis, depression, mania or anorexia nervosa;

- acute or chronic organ or systemic inflammatory disease;

- endocrinopathy, other than primary thyroidal failure receiving replacement;

- although fulvestrant has no known intrinsic estrogenicity, for safety reasons we
include contraindication to short-term estrogen exposure; e.g.,estrogen-sensitive
neoplasia, undiagnosed vaginal bleeding, deep-venous thrombosis, stroke or
threatened stroke, clinical evidence of atherosclerotic heart disease, including
myocardial infarction and/or angina, refractory high blood pressure, severe type IV
hyperlipidemia:

- nightshift work or recent transmeridian travel (exceeding 3 time zones within 5 days
of admission);

- systemic anticoagulation other than anti platelet therapy (in view of i.m. injections
of fulvestrant); history of bleeding diathesis (ie; disseminated coagulation (DIC),
clotting factor deficiency

- acute weight change (> 3 kg in 6 weeks); and/or

- unwillingness to provide written informed consent.

- Platelets less than 200 x 109 /L

- International normalization ratio(INR) (Prothrombin time) greater than 1.6

- Total bilirubin greater than 1.5 x ULRR

- ALT or AST greater than 2.5 xULRR if no demonstrable liver metastases or greater

- History or hypersensitivity to active or inactive excipients of fulvestrant (ie;
castor oil or Mannitol).