Estradiol-Receptor Blockade in Older Men and Women

Inclusion: 1. 40 healthy women and men (ages 50 to 80 y); women will be post-menopausal (clinically defined by E2 \< 50 pg/mL, FSH \> 30Iu/L) 2. BMI 18-35 kg/m2 3. community dwelling; and voluntarily consenting Exclusion: 1. recent use of psychotropic or neuroactive drugs (within five biological half-live); 2. obesity (outside weight range above); 3. Laboratory test results not deemed physician acceptable, viz potassium \<3.5 mEq/L, magnesium \<1.5 mEq/L, triglycerides \> 300, BUN \>30 or creatinine \> 1.5 mg/dL, liver functions tests twice upper limit of normal, anemia (hemoglobin must meet Blood Bank requirements - Hgb ≥ 12.5 g/dL) 4. drug or alcohol abuse, psychosis, depression, mania or severe anxiety; 5. acute or chronic organ-system disease, including renal failure (creatinine \> 1.5 mg/dL) 6. endocrinopathy, other than primary thyroidal failure receiving replacement 7. nightshift work or recent transmeridian travel (exceeding 3 time zones within 7 days of admission), 8. acute weight change (loss or gain of \> 2 kg in 6 weeks); 9. allergy to toremifene 10. unwillingness to provide written informed consent. 11. PSA \> 4.0 ng/mL in men 12. History or suspicion of prostatic disease (elevated PSA, indeterminate nodule or mass, obstructive uropathy, or breast cancer), 13. Other carcinoma (excluding localized basal cell carcinoma removed or surgically treated with no recurrence). 14. History of thrombotic arterial disease (stroke, TIA, MI, angina) or deep vein thrombophlebitis. 15. History of CHF, cardiac arrhythmias, congenital QT prolongation, and medications used to treat cardiac arrhythmias or other strong CYP3A4 inhibitors.