Estradiol-Receptor Blockade in Older Men and Women

• Status: Completed
• Trial end date: 2016-05-01
• Target enrollment: 0
• Participant gender: All

Summary

Repletion of testosterone (Te) in older men drives GH secretion after its aromatization to estradiol (E2), which acts via the estrogen receptor (ER). Conversely, we postulate that estrogen deprivation in postmenopausal women attenuates growth hormone (GH) secretion and insulin-like growth factor-1 (IGF-I) production, thus favoring development of metabolic syndrome in men treated with toremifene, a new estrogen antagonist used adjunctively in prostatic cancer

• Phase: Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Mayo Clinic
• Treatments: Estradiol; Toremifene

Criteria

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.